Effects of Metformin Hydrochloride (HCl) in Combination With Colesevelam HCl, Compared to Metformin HCl Alone, in Patients With Type 2 Diabetes Mellitus and the Effects of Colesevelam HCl on Lipids and Glucose on Pre-diabetic Patients.
Sponsor
Daiichi Sankyo, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00570739
Collaborator
(none)
502
31
4
18
16.2
0.9
Study Details
Study Description
Brief Summary
This is a 16-week double-blind, placebo-controlled (for colesevelam hydrochloride (HCl)) study in the type 2 diabetic subjects and pre-diabetic subjects. Diabetic participants will also be treated with open label, background,metformin HCl. Two-hundred sixty subjects with type 2 diabetes (T2DM) and 200 pre-diabetic subjects are planned to be be enrolled. Qualified subjects with T2DM will be randomized 1:1 to receive metformin HCl plus colesevelam HCl or metformin HCl plus placebo matching colesevelam HCl. Qualified pre-diabetic subjects will be randomized 1:1 to receive colesevelam HCl or matching placebo.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
502 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Effects of Metformin HCl in Combination With Colesevelam HCl, Compared to Metformin HCl Alone, as Initial Therapy in Drug naïve Subjects With Type 2 Diabetes Mellitus, and the Effects of Colesevelam HCl on the Lipid Profile in Subjects With Pre Diabetes
Study Start Date
:
Nov 1, 2007
Actual Primary Completion Date
:
Apr 1, 2009
Actual Study Completion Date
:
May 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Diabetic Participants: Metformin HCl+Placebo for Colesevelam Participants will receive either 850 mg or 1700 mg of metformin HCl, depending on tolerability + 6 placebo tablets matching colesevelam 625 mg. Study medication is to be administered once daily for 16 weeks. |
Drug: Metformin HCl and Colesevelam Placebo
One or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg placebo tablets once daily for 16 weeks
|
| Experimental: Diabetic participants: Metformin HCl + Colesevelam Participants will receive either 850 mg or 1700 mg of metformin HCl, depending on tolerability + 6 colesevelam tablets, 625 mg. Study medication is to be administered once daily for 16 weeks. |
Drug: Metformin HCl tablets and Colesevelam tablets
One or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg tablets once daily for 16 weeks
|
| Placebo Comparator: Pre-diabetic Participants: Colesevelam Placebo Participants will receive 6 placebo tablets matching colesevelam 625 mg. Study medication is to be administered once daily for 16 weeks. |
Drug: Colesevelam placebo
Six colesevelam 625 mg placebo tablets will be given once a day for 16 weeks
|
| Experimental: Pre-diabetes Participants: Colesevelam Participants will receive 6 colesevelam tablets, 625 mg. Study medication is to be administered once daily for 16 weeks. |
Drug: Colesevelam
Six colesevelam 625 mg tablets will be given once a day for 16 weeks.
|
Outcome Measures
Primary Outcome Measures
- Percent Change of Hemoglobin A1C (HbA1C) From Baseline to 16 Weeks When Given as Initial Therapy to Drug-naïve, Diabetic Subjects. [Baseline to 16 weeks]
- Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
Secondary Outcome Measures
- Percent Change in Hemoglobin A1C (HbA1C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12 and 16 Weeks. [Baseline to 4, 8, 12, and 16 weeks]
- Fasting Plasma Glucose When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks [Baseline to 4, 8, 12, and 16 weeks]
- Fasting Insulin When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks [Baseline to 4, 8, 12, and 16 weeks]
- Fasting C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 weeks]
- 30 Minute Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 weeks]
- 1 Hour Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 weeks]
- 2 Hour Post-Meal Glucose Levels to in Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 weeks]
- 2 Hour Post-Meal Insulin Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 weeks]
- 2 Hour Post-Meal C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 weeks]
- The Percent Change of Low Density Lipoprotein Cholesterol (LDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 weeks]
- Percent Change of Non-High Density Lipoprotein (Non-HDL) Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 weeks]
- Percent Change of High Density Lipoprotein Cholesterol(HDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 weeks]
- Percent Change of Total Cholesterol (TC) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 weeks]
- Percent Change of Triglycerides (TG)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 weeks]
- Percent Change of Apolipoprotein A-1 (Apo A-1) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 weeks]
- Percent Change of Apolipoprotein B (Apo B)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 weeks]
- Percent Change of Apolipoprotein C3 (Apo C3)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 weeks]
- Change in the Levels of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 weeks]
- Change in the Size of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change in the Calculated Total Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change in the Calculated Very Low Density Lipoprotein Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.
- Change in the Calculated High Density Lipoprotein Cholesterol When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.
- Percent of Subjects Achieving HbA1c Goal of <7.0% at Weeks 4, 8, 12, and 16 if Baseline HbA1c Was > or = to 7.0% When Given to Drug-naïve, Diabetics [Baseline to 4, 8, 12, and 16 Weeks]
- Percent of Subject Achieving HbA1c Goal of <6.5% at Weeks 4, 8, 12, and 16 When Given to Drug-naïve, Diabetic Subjects [Baseline to 4, 8, 12 and 16 weeks]
- Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 When Given to Drug-naïve, Diabetic Subjects [Baseline to Weeks 8, and 16]
- Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol Goal of <70 mg/dL at Weeks 8, 16 When Given as to Drug-naïve, Diabetics [Baseline to Weeks 8, and 16]
- Change in Body Weight When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change in Waist-to-Hip Ratio When Given to Drug-Naive Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change in Plasma Glucose Area Under the Curve (0 to 120 Minutes) From the Baseline Glucose Tolerance Test (GTT) to the 16 Week GTT [Baseline vs. 16 Weeks]
- Percent Change of Various Calculated Lipid Parameters When Given as Initial Therapy to Drug-naïve, Diabetic From Baseline to 16 Weeks Subjects [Baseline to 16 Weeks]
These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.
- Percent of Subjects Achieving 2-Hr. Post Meal Glucose Goal of <180 mg/dL When Given to Drug-naïve, Diabetic Subjects From Baseline to Week 16 [Baseline to Week 16]
- Percent of Subjects Achieving Hs-C-Reactive Protein Goal of <2.0 mg/L When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Percent Change in Low Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 Weeks]
- Percent Change in Non-High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 Weeks]
- Percent Change in High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 Weeks]
- Percent Change in Total Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 Weeks]
- Percent Change in Apolipoprotein A-1 in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 Weeks]
- Percent Change in Apolipoprotein B in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 Weeks]
- Percent Change in Apolipoprotein CIII in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 Weeks]
- Percent Change in Triglycerides in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks [Baseline to 8, and 16 Weeks]
- Percent Change in Hs-C-Reactive Protein in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline 16 Weeks]
- Level of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Particle Size of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change of Various Calculated Lipid Parameters in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.
- Percent Change of HbA1c in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks [Baseline to 4, 8, 12, and 16 Weeks]
- Percent Change of Fasting Plasma Glucose in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks [Baseline to 4, 8, 12, and 16 weeks]
- Percent Change of Fasting Insulin in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks [Baseline to 4, 8, 12, and 16 Weeks]
- Change of Fasting C-peptide Levels in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change of Glucose Levels 30 Minutes Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change of Glucose Levels 1 Hour Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change of Glucose Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change of Insulin Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change of C-Peptide Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects [Baseline to 8, and 16 Weeks]
- Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <70 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects [Baseline to 8, and 16 Weeks]
- Change in Body Weight in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Change in Waist-to-Hip Ratio in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Area Under the Curve for Plasma Glucose From 0 to 120 Minutes During the Oral Glucose Tolerance Tests in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Percent Achievement of <140 mg/dL Plasma Glucose 2 Hours Post the Oral Glucose Tolerance Test in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was >or= to 140 mg/dL From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Percent Achievement of <110 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 110 mg/dL From Baseline to 4, 8, 12, and 16 Weeks [Baseline to 4, 8, 12, and 16 Weeks]
- Percent Achievement of <100 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 100 mg/dL From Baseline to 4, 8, 12 and 16 Weeks [Baseline to 4, 8, 12 and 16 weeks]
- Percent Achievement of <140 mg/dL Plasma Glucose Post 2 Hour Glucose Tolerance Test and Fasting Plasma Glucose <110 mg/dL in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Percent Achievement of Hs-C-Reactive Protein <2.0 mg/L in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 2.0 mg/L From Baseline to 16 Weeks [Baseline to 16 Weeks]
- Percent of Subjects Meeting Type 2 Diabetes Criteria (Fasting Plasma Glucose >or= to 126 mg/dL or Plasma Glucose >or= to 200 mg/dL Post 2 Hr Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks [Baseline to 16 Weeks]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 79 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age 18 to 79 years, inclusive.
-
HbA1C in the range of greater than or equal to 6.5 percent to small than or equal to 10.0 percent, to be enrolled in the T2DM cohort.
-
2-hour post 75 g OGTT glucose levels in the range of:
-
greater than or equal to 200 mg/dL to be enrolled in the T2DM cohort, or
-
greater than or equal to 140 to 200 mg/dL to be enrolled in the pre-diabetes cohort.
-
FPG levels in the range of:
-
greater than or equal to 126 mg/dL to be enrolled in the T2DM cohort, or
-
greater than or equal to 110 to smaller than or equal to 125 mg/dL to be enrolled in the pre-diabetes cohort.
-
LDL-C levels greater than or equal to 100 mg/dL.
-
Drug-naïve, defined as having never received treatment for T2DM or not having received antidiabetic drug therapy during the 3 months prior to screening visit.
-
Previous diagnosis of:
-
T2DM or prediabetes, to be enrolled in the respective cohorts, or
-
CHD, CVD, and/or primary hypercholesterolemia + BMI greater than or equal to 25 mg/kg2 to be screened for T2DM or pre-diabetes.
-
Understanding of the study procedures and agreement to participate in the study by giving written informed consent at screening visit.
-
Women may be enrolled if all 3 of the following criteria (in addition to the above criteria)are met:
-
They are not pregnant (women of childbearing potential must have a negative serum pregnancy test [serum beta human chorionic gonadotropin )] at screening visit);
-
They are not breast-feeding; and
-
They do not plan to become pregnant during the study.
-
In addition to all of the above criteria, women must also meet 1 of the following 3 criteria to be enrolled:
-
They have been post-menopausal for at least 1 year; or
-
They are of childbearing potential and will practice 1 of the following methods of birth control throughout the study: oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide; or female condom plus spermicide. Methods of contraception that are not acceptable are partner's use of condoms or partner's vasectomy.
Exclusion Criteria:
-
History of type 1 diabetes and/or history of acute or chronic metabolic acidosis, including diabetic ketoacidosis.
-
History of chronic (requiring daily for greater than 2 months) use of insulin therapy, except for the treatment of gestational diabetes.
-
Current or prior (within the past 3 months) treatment with an oral antidiabetic drug.
-
Current or prior (within the past 3 months) treatment with colesevelam HCl (WelChol), colestipol, colestimide, or cholestyramine.
-
History of dysphagia, swallowing disorders, or intestinal motility disorder.
-
Any serious disorder, including pulmonary, hepatic, gastrointestinal (including clinically significant malabsorption), uncontrolled endocrine/metabolic, hematologic/oncologic (within the last 5 years), neurologic, and psychiatric diseases, that would interfere with the conduct of the study or interpretation of the data.
-
Acute coronary syndrome (eg, myocardial infarction or unstable angina), coronary intervention (coronary artery bypass graft or percutaneous transluminal coronary angioplasty or similar procedure), congestive heart failure (requiring pharmacological treatment), or transient ischemic attack within 3 months of screening visit.
-
History of pancreatitis.
-
History of acquired immune deficiency syndrome or human immunodeficiency virus.
-
History of drug or alcohol abuse within the past 2 years.
-
Hospitalization for any cause within 14 days prior to screening visit.
-
History of an allergic or toxic response to colesevelam HCl or any of its components.
-
Known hypersensitivity to metformin HCl.
-
Serum TG greater than or equal to 500 mg/dL.
-
Body mass index (BMI) greater than 40 kg/m2 .
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | ||
| 2 | Los Gatos | California | United States | ||
| 3 | Tarzana | California | United States | ||
| 4 | Ocala | Florida | United States | ||
| 5 | Pocatello | Idaho | United States | ||
| 6 | Gary | Indiana | United States | ||
| 7 | New Orleans | Louisiana | United States | 70112 | |
| 8 | Olive Branch | Mississippi | United States | ||
| 9 | Dundee | New York | United States | ||
| 10 | West Seneca | New York | United States | ||
| 11 | Statesville | North Carolina | United States | ||
| 12 | Kent | Ohio | United States | ||
| 13 | Marion | Ohio | United States | ||
| 14 | Portland | Oregon | United States | ||
| 15 | Corpus Christi | Texas | United States | ||
| 16 | Dallas | Texas | United States | ||
| 17 | San Antonio | Texas | United States | ||
| 18 | Barranquilla | Atlántico | Colombia | ||
| 19 | Bogota | Cundinamarca | Colombia | ||
| 20 | Bucaramanga | Santander | Colombia | ||
| 21 | Mumbai | Dadar | India | ||
| 22 | Durgapura | Jaipur | India | ||
| 23 | Bangalore | Karnataka | India | ||
| 24 | Cochin | Kerala | India | ||
| 25 | Nasik | Mahārāshtra | India | ||
| 26 | Las Palmas | Chihuahua | Mexico | ||
| 27 | Delegacion | Cuauhtemoc | Mexico | ||
| 28 | Guadalajara | Jalisco | Mexico | ||
| 29 | Monterrey | Nuevo Leon | Mexico | ||
| 30 | Hermosillo | Sonora | Mexico | ||
| 31 | Merida | Yucatan | Mexico |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
Investigators
- Study Director: Michael Jones, DSI
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00570739
Other Study ID Numbers:
- WEL-411
- IND 68,466
First Posted:
Dec 11, 2007
Last Update Posted:
Jul 27, 2010
Last Verified:
Jul 1, 2010
Keywords provided by ,
,
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Two cohorts of participants, type 2 diabetics (T2DM) and pre-diabetics, were recruited from 07 Jan 2008 to 15 Dec 2008. The sites were located in Colombia, India, Mexico, and the USA. The sites included private physician offices, group practices, clinics, hospitals, institutes, and university centers. |
|---|---|
| Pre-assignment Detail | Due to the different metabolic nature of the two groups the "Total" column under Baseline Characteristics is populated with data for the diabetic group, except where the total could be obtained by just adding the number of participants. Please note: in the outcomes section, LOCF=Last Observation carried forward |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin | Pre-diabetic Group: Placebo | Pre-diabetic Group: Colesevelam |
|---|---|---|---|---|
| Arm/Group Description | This group received 6 matching colesevalm placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. This treatment duration was 16 weeks. | This group received 6 colevevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. This treatment duration was 16 weeks. | This group was given 6 placebo tablets once a day. They matched the colesevelam tablets. This treatment duration was 16 weeks. | This group was given 6 colesevelam tablets, 625mg, once a day. This treatment duration was 16 weeks. |
| Period Title: Overall Study | ||||
| STARTED | 141 | 145 | 108 | 108 |
| COMPLETED | 120 | 124 | 92 | 96 |
| NOT COMPLETED | 21 | 21 | 16 | 12 |
Baseline Characteristics
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin | Pre-diabetic Group: Placebo | Pre-diabetic Group: Colesevelam | Total |
|---|---|---|---|---|---|
| Arm/Group Description | This group received 6 matching colesevalm placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. This treatment duration was 16 weeks. | This group received 6 colevevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. This treatment duration was 16 weeks. | This group received 6 colesevelam matching placebo tablets once per day for 16 weeks | This group received 6 colesevelam tablets, 625mg, once per day for 16 weeks. | Total of all reporting groups |
| Overall Participants | 141 | 145 | 108 | 108 | 502 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
53.9
(10.11)
|
52.7
(11.46)
|
55.7
(11.14)
|
53.3
(12.27)
|
53.3
(10.81)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
85
60.3%
|
76
52.4%
|
81
75%
|
68
63%
|
310
61.8%
|
| Male |
56
39.7%
|
69
47.6%
|
27
25%
|
40
37%
|
192
38.2%
|
| Race/Ethnicity, Customized (Number) [Number] | |||||
| Asian |
30
21.3%
|
32
22.1%
|
15
13.9%
|
14
13%
|
91
18.1%
|
| Black/African American |
1
0.7%
|
3
2.1%
|
1
0.9%
|
1
0.9%
|
6
1.2%
|
| White |
20
14.2%
|
21
14.5%
|
14
13%
|
11
10.2%
|
66
13.1%
|
| Hispanic |
90
63.8%
|
89
61.4%
|
78
72.2%
|
82
75.9%
|
339
67.5%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
30
21.3%
|
30
20.7%
|
17
15.7%
|
16
14.8%
|
93
18.5%
|
| Mexico |
56
39.7%
|
58
40%
|
40
37%
|
41
38%
|
195
38.8%
|
| Colombia |
25
17.7%
|
26
17.9%
|
36
33.3%
|
37
34.3%
|
124
24.7%
|
| India |
30
21.3%
|
31
21.4%
|
15
13.9%
|
14
13%
|
90
17.9%
|
| Previously diagnosed with neither diabetes nor pre-diabetes (Participant) [Number] | |||||
| Number [Participant] |
14
|
15
|
26
|
22
|
77
|
| Previously diagnosed with pre-diabetes (Participant) [Number] | |||||
| Number [Participant] |
17
|
21
|
81
|
85
|
204
|
| Previously diagnosed with type 2 diabetes (Participant) [Number] | |||||
| Number [Participant] |
110
|
109
|
1
|
1
|
221
|
| Body Mass Index (kg/m squared) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kg/m squared] |
29.78
(4.44)
|
30.58
(4.669)
|
30.82
(4.18)
|
30.93
(4.89)
|
30.19
(4.57)
|
| Fasting glucose (mg/dL) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [mg/dL] |
145.7
(37.54)
|
153.4
(39.04)
|
106.8
(14.80)
|
104.1
(11.33)
|
149.6
(38.43)
|
| Fasting insulin (uIU/mL) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [uIU/mL] |
12.82
(8.44)
|
13.86
(15.75)
|
11.03
(5.55)
|
13.12
(8.75)
|
13.34
(12.66)
|
| Glucose 2 hours after meal (mg/dL) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [mg/dL] |
220.3
(58.68)
|
234.7
(71.36)
|
153.7
(39.81)
|
153.7
(37.90)
|
227.7
(65.74)
|
| Height (cm) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [cm] |
160.6
(10.64)
|
162.3
(9.67)
|
159.1
(9.95)
|
160.8
(9.96)
|
161.5
(10.18)
|
| Hemoglobin A1c (Percent) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Percent] |
7.53
(0.94)
|
7.76
(1.04)
|
6.07
(0.45)
|
6.02
(0.46)
|
7.65
(1.0)
|
| Low Density Lipoprotein Cholesterol (mg/dL) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [mg/dL] |
135.5
(26.66)
|
129.1
(23.08)
|
136.8
(28.48)
|
132.8
(23.88)
|
132.2
(25.07)
|
| Weight (kg) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kg] |
77.26
(16.17)
|
80.84
(15.53)
|
78.18
(13.76)
|
80.63
(18.02)
|
79.08
(15.92)
|
Outcome Measures
| Title | Percent Change in Hemoglobin A1C (HbA1C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12 and 16 Weeks. |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed equals the full analysis set. The full analysis set included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. This analysis set was used for the summary and analysis of all efficacy variables. LOCF was not used. |
| Arm/Group Title | Type 2 Diabetes Group:Placebo+Metformin | Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 128 | 129 |
| Baseline to 4 weeks:Pla+Met, N=128, Col+Met N=129 |
-0.38
(0.044)
|
-0.53
(0.044)
|
| Baseline to 8 weeks:Pla+Met, N=123, Col+Met N=125 |
-0.67
(0.055)
|
-0.84
(0.055)
|
| Baseline to 12 weeks:Pla+Met, N=115, Col+Met N=123 |
-0.86
(0.062)
|
-1.05
(0.059)
|
| Baseline to 16 weeks:Pla+Met, N=118, Col+Met N=122 |
-0.92
(0.064)
|
-1.17
(0.063)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 4 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0123 |
| Comments | P-Value is for the LS mean difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.27 to -0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0201 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.18 | |
| Confidence Interval |
(2-Sided) 95% -0.33 to -0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0239 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.19 | |
| Confidence Interval |
(2-Sided) 95% -0.36 to -0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0046 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.25 | |
| Confidence Interval |
(2-Sided) 95% -0.42 to -0.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Fasting Plasma Glucose When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo+Metformin | Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 130 | 131 |
| baseline to 4 weeks Pla+Met N=130, Col+Met N=131 |
-19.0
(2.31)
|
-24.0
(2.30)
|
| baseline to 8 weeks:Pla+Met N=122, Col+Met N=126 |
-24.3
(1.97)
|
-27.6
(1.94)
|
| baseline to 12 weeks:Pla+Met N=121, Col+Met N=125 |
-27.3
(2.21)
|
-28.4
(2.18)
|
| baseline to 16 weeks:Pla+Met N=119, Col+Met N=124 |
-28.0
(2.21)
|
-30.5
(2.16)
|
| baseline to 16wks LOCF:Pla+Met N=137,Col+Met N=138 |
-25.9
(2.19)
|
-28.0
(2.18)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 4 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1112 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.1 | |
| Confidence Interval |
(2-Sided) 95% -11.3 to 1.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2167 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -3.3 | |
| Confidence Interval |
(2-Sided) 95% -8.6 to 2.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7269 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -7.0 to 4.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4063 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.5 | |
| Confidence Interval |
(2-Sided) 95% -8.4 to 3.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks (LOCF) | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4909 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.1 | |
| Confidence Interval |
(2-Sided) 95% -8.0 to 3.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Fasting Insulin When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group:Placebo+Metformin | Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 127 | 127 |
| Baseline to 4 weeks:Pla+Met, N=127, Col+Met N=127 |
-2.124
(0.7219)
|
-2.427
(0.7219)
|
| Baseline to 8 weeks:Pla+Met, N=124, Col+Met N=126 |
-1.992
(0.5407)
|
-3.007
(0.5376)
|
| Baseline to 12 weeks:Pla+Met, N=117, Col+Met N=123 |
-2.204
(0.5159)
|
-3.708
(0.5048)
|
| Baseline to 16 weeks:Pla+Met, N=119, Col+Met N=124 |
-2.978
(0.7379)
|
-2.802
(0.7217)
|
| Baseline to16wks LOCF:Pla+Met,N=137,Col+Met N=138 |
-2.847
(0.6655)
|
-2.637
(0.6644)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 4 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7606 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.303 | |
| Confidence Interval |
(2-Sided) 95% -2.259 to 1.653 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1782 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.015 | |
| Confidence Interval |
(2-Sided) 95% -2.477 to 0.447 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0332 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.504 | |
| Confidence Interval |
(2-Sided) 95% -2.887 to -0.121 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8610 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.176 | |
| Confidence Interval |
(2-Sided) 95% -1.805 to 2.158 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks (LOCF) | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8196 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.210 | |
| Confidence Interval |
(2-Sided) 95% -1.599 to 2.019 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Fasting C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 120 | 124 |
| Baseline to 16 Weeks |
-0.295
(0.0695)
|
-0.449
(0.0683)
|
| Baseline to 16Wks LOCF Pla+Met N=133,Col+Met N=134 |
-0.284
(0.0650)
|
-0.426
(0.0644)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1078 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.153 | |
| Confidence Interval |
(2-Sided) 95% -0.340 to 0.034 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks (LOCF) | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1146 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.141 | |
| Confidence Interval |
(2-Sided) 95% -0.317 to 0.035 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 30 Minute Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 120 | 123 |
| Baseline to 16 weeks |
-33.1
(3.46)
|
-33.1
(3.43)
|
| Baseline to 16Wks LOCF Pla+Met N=133,Col+Met N=132 |
-29.4
(3.44)
|
-30.4
(3.45)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9933 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -9.3 to 9.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8203 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -10.5 to 8.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 1 Hour Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 118 | 120 |
| Baseline to 16 Weeks |
-35.0
(3.91)
|
-41.9
(3.88)
|
| Baseline to 16 Weeks LOCF:N=131 Pla; N=129 Colesev |
-31.4
(3.92)
|
-39.1
(3.94)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1950 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.0 | |
| Confidence Interval |
(2-Sided) 95% -17.5 to 3.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1583 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.7 | |
| Confidence Interval |
(2-Sided) 95% -18.3 to 3.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 2 Hour Post-Meal Glucose Levels to in Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 115 | 120 |
| Baseline to 16 Weeks |
-33.0
(4.11)
|
-38.14
(4.02)
|
| Baseline to 16 Weeks LOCF: Pla N=129, Met N=127 |
-29.4
(4.18)
|
-36.2
(4.14)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3663 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.1 | |
| Confidence Interval |
(2-Sided) 95% -16.1 to 6.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2524 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.6 | |
| Confidence Interval |
(2-Sided) 95% -17.9 to 4.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 2 Hour Post-Meal Insulin Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 116 | 118 |
| Baseline to 16 Weeks |
-11.601
(3.2794)
|
-10.551
(3.2370)
|
| Baseline to 16 Weeks LOCF: Pla N=129, Met N=127 |
-8.592
(3.4395)
|
-10.156
(3.4399)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8158 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.051 | |
| Confidence Interval |
(2-Sided) 95% -7.828 to 9.929 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7433 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.565 | |
| Confidence Interval |
(2-Sided) 95% -10.966 to 7.836 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 2 Hour Post-Meal C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed = the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Results are presented for both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 117 | 121 |
| Baseline to 16 Weeks |
-0.317
(0.2424)
|
-0.102
(0.2373)
|
| Baseline to 16 Weeks LOCF: Pla N=129, Met N=130 |
-0.205
(0.2406)
|
-0.135
(0.2374)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5161 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.215 | |
| Confidence Interval |
(2-Sided) 95% -0.437 to 0.867 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8319 |
| Comments | P-Value is for the LS Mean Difference between treatment groups. | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.070 | |
| Confidence Interval |
(2-Sided) 95% -0.581 to 0.722 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | The Percent Change of Low Density Lipoprotein Cholesterol (LDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam+Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 122 | 124 |
| Baseline to 8 Weeks |
-5.83
(1.631)
|
-24.01
(1.614)
|
| Baseline to 16 Weeks: Pla N=119, Met N=124 |
-4.94
(1.852)
|
-22.02
(1.813)
|
| Baseline to 16 Weeks LOCF: Pla N=137, Met N=136 |
-5.11
(1.695)
|
-21.44
(1.700)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -18.19 | |
| Confidence Interval |
(2-Sided) 95% -22.61 to -13.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -17.08 | |
| Confidence Interval |
(2-Sided) 95% -22.09 to -12.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -16.33 | |
| Confidence Interval |
(2-Sided) 95% -20.96 to -11.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Non-High Density Lipoprotein (Non-HDL) Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 122 | 125 |
| Baseline to 8 Weeks |
-5.79
(1.327)
|
-18.19
(1.316)
|
| Baseline to 16 Weeks: Pla N=119, Met N=124 |
-5.08
(1.460)
|
-14.36
(1.436)
|
| Baseline to 16 Weeks LOCF: Pla N=137, Met N=136 |
-5.38
(1.338)
|
-13.70
(1.346)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -12.40 | |
| Confidence Interval |
(2-Sided) 95% -15.99 to -8.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -9.28 | |
| Confidence Interval |
(2-Sided) 95% -13.23 to -5.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Week LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.33 | |
| Confidence Interval |
(2-Sided) 95% -11.98 to -4.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of High Density Lipoprotein Cholesterol(HDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 122 | 125 |
| Baseline to 8 Weeks |
2.98
(1.506)
|
5.61
(1.488)
|
| Baseline to 16 Weeks: Pla N=119, Met N=124 |
7.46
(1.277)
|
8.78
(1.250)
|
| Baseline to 16 Weeks LOCF: Pla N=137, Met N=136 |
6.58
(1.160)
|
8.39
(1.165)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2026 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | 2.63 | |
| Confidence Interval |
(2-Sided) 95% -1.43 to 6.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4506 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.32 | |
| Confidence Interval |
(2-Sided) 95% -2.12 to 4.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2609 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.81 | |
| Confidence Interval |
(2-Sided) 95% -1.35 to 4.97 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Total Cholesterol (TC) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 122 | 125 |
| Baseline to 8 Weeks |
-4.46
(1.009)
|
-13.26
(1.000)
|
| Baseline to 16 Weeks: Pla N=119, Met=124 |
-2.85
(1.217)
|
-9.79
(1.197)
|
| Baseline to 16 Weeks LOCF: Pla N=137, Met=136 |
-3.22
(1.115)
|
-9.31
(1.121)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.81 | |
| Confidence Interval |
(2-Sided) 95% -11.53 to -6.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.94 | |
| Confidence Interval |
(2-Sided) 95% -10.23 to -3.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.09 | |
| Confidence Interval |
(2-Sided) 95% -9.14 to -3.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Triglycerides (TG)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 122 | 125 |
| Baseline to 8 Weeks |
-7.39
|
1.28
|
| Baseline to 16 Weeks: Pla N=119, Met N=124 |
-7.12
|
8.63
|
| Baseline to 16 Weeks LOCF: Pla N=137, Met N=136 |
-9.55
|
8.80
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0171 |
| Comments | The P-Value was from the non-parametric ANCOVA stratified by country. | |
| Method | ANCOVA | |
| Comments | The median difference was calculated using Hodges-Lehmann point estimate and corresponding 95% CI was constructed using the method of Moses. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.05 | |
| Confidence Interval |
(2-Sided) 95% -0.33 to 13.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The P-Value was from the non-parametric ANCOVA stratified by country. | |
| Method | ANCOVA | |
| Comments | The median difference was calculated using Hodges-Lehmann point estimate and corresponding 95% CI was constructed using the method of Moses. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 17.71 | |
| Confidence Interval |
(2-Sided) 95% 9.66 to 25.54 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The P-Value was from the non-parametric ANCOVA stratified by country. | |
| Method | ANCOVA | |
| Comments | The median difference was calculated using Hodges-Lehmann point estimate and corresponding 95% CI was constructed using the method of Moses. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 18.62 | |
| Confidence Interval |
(2-Sided) 95% 11.18 to 25.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Apolipoprotein A-1 (Apo A-1) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 118 | 124 |
| Baseline to 8 Weeks |
3.30
(1.047)
|
6.12
(1.027)
|
| Baseline to 16 Weeks: Pla N=113, Met N=120 |
4.86
(1.052)
|
8.51
(1.024)
|
| Baseline to 16 Weeks LOCF: Pla N=133, Met N=134 |
4.02
(0.957)
|
8.45
(0.953)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0496 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.81 | |
| Confidence Interval |
(2-Sided) 95% 0.0 to 5.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0117 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.65 | |
| Confidence Interval |
(2-Sided) 95% 0.82 to 6.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.43 | |
| Confidence Interval |
(2-Sided) 95% 1.83 to 7.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Apolipoprotein B (Apo B)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 118 | 124 |
| Baseline to 8 Weeks |
-4.59
(1.184)
|
16.15
(1.158)
|
| Baseline to 16 Weeks: Pla N=113, Met N=120 |
-3.89
(1.340)
|
-13.42
(1.307)
|
| Baseline to 16 Weeks LOCF: Pla N=133, Met N=134 |
-4.20
(1.242)
|
-12.17
(1.239)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -11.56 | |
| Confidence Interval |
(2-Sided) 95% -14.74 to -8.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -9.53 | |
| Confidence Interval |
(2-Sided) 95% -13.14 to -5.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.97 | |
| Confidence Interval |
(2-Sided) 95% -11.35 to -4.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Apolipoprotein C3 (Apo C3)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 122 | 125 |
| Baseline to 8 Weeks |
0.01
(2.527)
|
12.58
(2.495)
|
| Baseline to 16 Weeks: Pla N=117, Met N=120 |
4.06
(2.932)
|
18.58
(2.871)
|
| Baseline to 16 Weeks LOCF: Pla N=136, N=136 |
2.82
(2.621)
|
17.89
(2.620)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 12.57 | |
| Confidence Interval |
(2-Sided) 95% 5.76 to 19.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 14.52 | |
| Confidence Interval |
(2-Sided) 95% 6.64 to 22.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 15.08 | |
| Confidence Interval |
(2-Sided) 95% 7.95 to 22.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in the Levels of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks | Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF) | Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 119 | 119 | 133 | 129 |
| Total Very Low Density Lipoprotein (VLDL) Particle |
-4.03
(2.361)
|
2.81
(2.355)
|
-3.71
(2.167)
|
2.68
(2.188)
|
| VLDL Chylomicron Particles |
-0.58
(0.554)
|
1.73
(0.552)
|
-0.58
(0.507)
|
1.76
(0.511)
|
| Medium VLDL Particles |
-2.31
(1.496)
|
4.84
(1.492)
|
-2.28
(1.383)
|
4.85
(1.396)
|
| Small VLDL Particles |
-1.12
(1.536)
|
-4.00
(1.532)
|
-0.83
(1.413)
|
-4.06
(1.426)
|
| Total Low Density Lipoprotein (LDL) Particles |
-104.0
(27.04)
|
-303.3
(27.05)
|
-109.5
(25.49)
|
-295.5
(25.77)
|
| Intermediate Density Lipoprotein Particles |
-9.6
(4.24)
|
-21.3
(4.24)
|
-8.9
(4.03)
|
-19.6
(4.08)
|
| Large LDL Particles |
52.1
(15.74)
|
-25.5
(15.69)
|
45.1
(14.60)
|
-24.2
(14.73)
|
| Small LDL Particles |
-146.9
(31.63)
|
-256.7
(31.63)
|
-145.9
(29.52)
|
-252.7
(29.84)
|
| Medium Small LDL Particles |
-32.0
(7.16)
|
-48.2
(7.15)
|
-30.8
(6.72)
|
-46.2
(6.78)
|
| Very Small LDL Particles |
-115.0
(24.96)
|
-208.7
(24.97)
|
-115.3
(23.31)
|
-206.6
(23.57)
|
| Total High Density Lipoprotein (HDL) Particles |
1.47
(0.352)
|
2.41
(0.351)
|
1.34
(0.332)
|
2.35
(0.335)
|
| Large HDL Particles |
0.64
(0.160)
|
1.09
(0.161)
|
0.55
(0.153)
|
1.00
(0.155)
|
| Medium HDL Particles |
-0.19
(0.275)
|
0.50
(0.274)
|
-0.26
(0.259)
|
0.59
(0.261)
|
| Small HDL Particles |
1.04
(0.385)
|
0.74
(0.384)
|
1.05
(0.362)
|
0.70
(0.366)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Total Very Low Density Lipoprotein (VLDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0363 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 6.84 | |
| Confidence Interval |
(2-Sided) 95% 0.44 to 13.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Total Very Low Density Lipoprotein (VLDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0347 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 6.39 | |
| Confidence Interval |
(2-Sided) 95% 0.46 to 12.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | VLDL Chylomicron Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0028 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.31 | |
| Confidence Interval |
(2-Sided) 95% 0.80 to 3.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | VLDL Chylomicron Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0010 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.34 | |
| Confidence Interval |
(2-Sided) 95% 0.96 to 3.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Medium VLDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0006 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.13 | |
| Confidence Interval |
(2-Sided) 95% 3.10 to 11.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Medium VLDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.13 | |
| Confidence Interval |
(2-Sided) 95% 3.35 to 10.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Small VLDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1750 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.88 | |
| Confidence Interval |
(2-Sided) 95% -7.04 to 1.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Small VLDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1007 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -3.23 | |
| Confidence Interval |
(2-Sided) 95% -7.10 to 0.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Total Low Density Lipoprotein (LDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -199.3 | |
| Confidence Interval |
(2-Sided) 95% -272.9 to -125.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Total Low Density Lipoprotein (LDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -186.1 | |
| Confidence Interval |
(2-Sided) 95% -255.9 to -116.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Intermediate Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0466 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -11.7 | |
| Confidence Interval |
(2-Sided) 95% -23.3 to -0.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Intermediate Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0570 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -10.7 | |
| Confidence Interval |
(2-Sided) 95% -21.8 to 0.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Large LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -77.7 | |
| Confidence Interval |
(2-Sided) 95% -120.3 to -35.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Large LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -69.3 | |
| Confidence Interval |
(2-Sided) 95% -109.2 to -29.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0124 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -109.9 | |
| Confidence Interval |
(2-Sided) 95% -195.8 to -23.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0098 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -106.8 | |
| Confidence Interval |
(2-Sided) 95% -187.6 to -26.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Medium Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1020 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -16.2 | |
| Confidence Interval |
(2-Sided) 95% -35.6 to 3.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Medium Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0997 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -15.4 | |
| Confidence Interval |
(2-Sided) 95% -33.8 to 3.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Very Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0069 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -93.7 | |
| Confidence Interval |
(2-Sided) 95% -161.6 to -25.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Very Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0052 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -91.4 | |
| Confidence Interval |
(2-Sided) 95% -155.2 to -27.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Total High Density Lipoprotein (HDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0524 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.94 | |
| Confidence Interval |
(2-Sided) 95% -0.01 to 1.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Total High Density Lipoprotein (HDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0301 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.01 | |
| Confidence Interval |
(2-Sided) 95% 0.10 to 1.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Large HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0416 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.45 | |
| Confidence Interval |
(2-Sided) 95% 0.02 to 0.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Large HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0333 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.46 | |
| Confidence Interval |
(2-Sided) 95% 0.04 to 0.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Medium HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0693 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.69 | |
| Confidence Interval |
(2-Sided) 95% -0.05 to 1.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Medium HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0187 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 95% 0.14 to 1.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Small HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5765 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.30 | |
| Confidence Interval |
(2-Sided) 95% -1.34 to 0.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Small HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4762 |
| Comments | P-Value is for the LS Mean Difference between treatment group | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.36 | |
| Confidence Interval |
(2-Sided) 95% -1.35 to 0.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in the Size of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks | Type 2 Diabetes Group: Colesevelam + Metformin for 16 Weeks | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF) | Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 119 | 119 | 133 | 129 |
| Very Low Density Lipoprotein Particles |
-0.80
(0.868)
|
1.41
(0.866)
|
-1.02
(0.796)
|
1.73
(0.804)
|
| Low Density Lipoprotein Particles |
0.20
(0.053)
|
0.15
(0.053)
|
0.19
(0.049)
|
0.15
(0.050)
|
| High Density Lipoprotein Particles |
0.08
(0.023)
|
0.17
(0.023)
|
0.08
(0.021)
|
0.17
(0.022)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Very Low Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0652 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.21 | |
| Confidence Interval |
(2-Sided) 95% -0.14 to 4.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Very Low Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0137 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.74 | |
| Confidence Interval |
(2-Sided) 95% 0.57 to 4.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Low Density Lipoprotien Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4726 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.20 to 0.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Low Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5715 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.17 to 0.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | High Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0083 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.08 | |
| Confidence Interval |
(2-Sided) 95% 0.02 to 0.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | High Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0022 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 95% 0.03 to 0.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in the Calculated Total Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 119 | 119 |
| Baseline to 16 Weeks |
-8.5
(6.44)
|
17.6
(6.43)
|
| Baseline to 16 Weeks LOCF: Pla N=133, Met N=129 |
-9.0
(5.88)
|
18.2
(5.93)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0036 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 26.0 | |
| Confidence Interval |
(2-Sided) 95% 8.6 to 43.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0010 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 27.2 | |
| Confidence Interval |
(2-Sided) 95% 11.2 to 43.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in the Calculated Very Low Density Lipoprotein Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary. |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 119 | 119 |
| Baseline to 16 Weeks |
-7.4
(6.36)
|
22.4
(6.34)
|
| Baseline to 16 Weeks LOCF: Pla N=133, Met N= 129 |
-7.9
(5.81)
|
22.9
(5.86)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 29.8 | |
| Confidence Interval |
(2-Sided) 95% 12.5 to 47.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 30.7 | |
| Confidence Interval |
(2-Sided) 95% 14.9 to 46.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in the Calculated High Density Lipoprotein Cholesterol When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary. |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 119 | 119 |
| Baseline to 16 Weeks |
3.2
(0.62)
|
5.8
(0.62)
|
| Baseline to 16 Weeks LOCF: Pla N=133, Met N=129 |
2.9
(0.59)
|
5.6
(0.60)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0033 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.6 | |
| Confidence Interval |
(2-Sided) 95% 0.9 to 4.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.8 | |
| Confidence Interval |
(2-Sided) 95% 1.2 to 4.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Hemoglobin A1C (HbA1C) From Baseline to 16 Weeks When Given as Initial Therapy to Drug-naïve, Diabetic Subjects. |
|---|---|
| Description | |
| Time Frame | Baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed equals the full analysis set. The full analysis set included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. This analysis set was used for the summary and analysis of all efficacy variables. LOCF was used. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 137 | 138 |
| Least Squares Mean (Standard Error) [Percentage of change of hemoglobin A1C] |
-0.83
(0.064)
|
-1.09
(0.064)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0035 |
| Comments | P-Value is for the LS mean difference between the treatment groups | |
| Method | ANCOVA | |
| Comments | The Ancova model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.44 to -0.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent of Subjects Achieving HbA1c Goal of <7.0% at Weeks 4, 8, 12, and 16 if Baseline HbA1c Was > or = to 7.0% When Given to Drug-naïve, Diabetics |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 90 | 93 |
| Baseline to 4 Weeks |
31.1
22.1%
|
25.8
17.8%
|
| Baseline to 8 Weeks: Pla N=87, Met N=91 |
47.1
33.4%
|
48.4
33.4%
|
| Baseline to 12 Weeks: Pla N=79, Met N=89 |
59.5
42.2%
|
64.0
44.1%
|
| Baseline to 16 Weeks: Pla N=83, Met N=87 |
59.0
41.8%
|
72.4
49.9%
|
| Baseline to 16 Weeks LOCF: Pla N=95, Met N=99 |
55.8
39.6%
|
66.7
46%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 4 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5848 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8147 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4957 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0467 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0589 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0049 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.9 | |
| Confidence Interval |
(2-Sided) 95% 1.38 to 6.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0092 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.44 | |
| Confidence Interval |
(2-Sided) 95% 1.25 to 4.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent of Subject Achieving HbA1c Goal of <6.5% at Weeks 4, 8, 12, and 16 When Given to Drug-naïve, Diabetic Subjects |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12 and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 122 | 125 |
| Baseline to 4 Weeks |
9.0
|
24.8
|
| Baseline to 8 Weeks: Pla N=118, Met N=121 |
23.7
|
36.4
|
| Baseline to 12 Weeks: Pla N=110, Met N=119 |
38.2
|
51.3
|
| Baseline to 16 Weeks: Pla N=114, Met N=118 |
44.7
|
55.9
|
| Baseline to 16 Weeks LOCF: Pla N=131, Met N=134 |
41.2
|
52.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 4 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Startified by country | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0280 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0414 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0840 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0589 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0095 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.19 | |
| Confidence Interval |
(2-Sided) 95% 1.21 to 3.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0088 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.08 | |
| Confidence Interval |
(2-Sided) 95% 1.20 to 3.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 When Given to Drug-naïve, Diabetic Subjects |
|---|---|
| Description | |
| Time Frame | Baseline to Weeks 8, and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 117 | 115 |
| Baseline to 8 Weeks |
16.2
11.5%
|
54.8
37.8%
|
| Baseline to 16 Weeks: Pla N=114, Met N=116 |
17.5
12.4%
|
50.0
34.5%
|
| Baseline to 16 Weeks LOCF: Pla N=131, Met N=127 |
18.3
13%
|
48.0
33.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 5.59 | |
| Confidence Interval |
(2-Sided) 95% 2.78 to 11.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 4.80 | |
| Confidence Interval |
(2-Sided) 95% 2.53 to 9.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol Goal of <70 mg/dL at Weeks 8, 16 When Given as to Drug-naïve, Diabetics |
|---|---|
| Description | |
| Time Frame | Baseline to Weeks 8, and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 122 | 124 |
| Baseline to 8 Weeks |
1.6
1.1%
|
13.7
9.4%
|
| Baseline to 16 Weeks: Pla N=119, Met N=124 |
5.0
3.5%
|
12.9
8.9%
|
| Baseline to 16 Weeks LOCF: Pla N=1137, Met N=136 |
4.4
3.1%
|
12.5
8.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0326 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0157 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by country | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0870 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.49 | |
| Confidence Interval |
(2-Sided) 95% 0.88 to 7.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00439 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.86 | |
| Confidence Interval |
(2-Sided) 95% 1.03 to 7.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Body Weight When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The total treatment duration was 16 weeks. |
| Measure Participants | 120 | 124 |
| Baseline to 16 Weeks |
-5.11
(0.564)
|
-4.91
(0.552)
|
| Baseline to 16 Weeks LOCF: Pla N=134, Met N=134 |
-4.71
(0.523)
|
-4.56
(0.519)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7959 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.20 | |
| Confidence Interval |
(2-Sided) 95% -1.32 to 1.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8371 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.15 | |
| Confidence Interval |
(2-Sided) 95% -1.28 to 1.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Waist-to-Hip Ratio When Given to Drug-Naive Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 120 | 124 |
| Baseline to 16 Weeks |
-0.0033
(0.00329)
|
-0.0067
(0.00323)
|
| Baseline to 16 Weeks LOCF: Pla N=134, Met N=134 |
-0.0030
(0.00306)
|
-0.0065
(0.00304)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4584 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.0033 | |
| Confidence Interval |
(2-Sided) 95% -0.0122 to 0.0055 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4039 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.0035 | |
| Confidence Interval |
(2-Sided) 95% -0.0118 to 0.0048 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed=the full analysis set (FAS). The FAS included randomized subjects who took at least 1 dose of randomized medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Last Observation Carried Forward was used for 16 week analyses. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 104 | 103 |
| Least Squares Mean (Standard Error) [Percentage of change in LDL-C] |
1.70
(2.054)
|
-13.89
(2.088)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -15.59 | |
| Confidence Interval |
(2-Sided) 95% -21.07 to -10.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Plasma Glucose Area Under the Curve (0 to 120 Minutes) From the Baseline Glucose Tolerance Test (GTT) to the 16 Week GTT |
|---|---|
| Description | |
| Time Frame | Baseline vs. 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 114 | 116 |
| Baseline to 16 Weeks |
-67.10
(6.305)
|
-77.56
(6.266)
|
| Baseline to 16 Weeks LOCF: Pla N=127, Met N=124 |
-60.34
(6.460)
|
-71.88
(6.524)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2289 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -10.46 | |
| Confidence Interval |
(2-Sided) 95% -27.53 to 6.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1997 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -11.54 | |
| Confidence Interval |
(2-Sided) 95% -29.22 to 6.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Various Calculated Lipid Parameters When Given as Initial Therapy to Drug-naïve, Diabetic From Baseline to 16 Weeks Subjects |
|---|---|
| Description | These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary. |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin | Type 2 Diabetes Group: Placebo + Metformin (LOCF) | Type 2 Diabetes Group:Colesevelam+Metformin(LOCF) |
|---|---|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 119 | 119 | 133 | 129 |
| Calculated Total Triglycerides |
1.67
|
14.48
|
0.99
|
15.11
|
| Calc.Very Low Density Lipoprotein Triglycerides |
7.48
|
30.28
|
6.62
|
31.34
|
| Calculated High Density Lipoprotein-Cholesterol |
9.51
|
17.86
|
8.70
|
17.39
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Calculated Triglycerides | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0144 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 12.81 | |
| Confidence Interval |
(2-Sided) 95% 2.57 to 23.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Calculated Triglycerides | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0037 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 14.12 | |
| Confidence Interval |
(2-Sided) 95% 4.63 to 23.61 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Calculated Very Low Density Lipoprotein Triglycerides | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0060 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 22.79 | |
| Confidence Interval |
(2-Sided) 95% 6.59 to 39.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Calculated Very Low Density Lipoprotein Triglycerides | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0013 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 24.72 | |
| Confidence Interval |
(2-Sided) 95% 9.71 to 39.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Calculated High Density Lipoprotein-Cholesterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 8.35 | |
| Confidence Interval |
(2-Sided) 95% 3.71 to 13.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Calculated High Density Lipoprotein-Cholesterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 8.69 | |
| Confidence Interval |
(2-Sided) 95% 4.27 to 13.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent of Subjects Achieving 2-Hr. Post Meal Glucose Goal of <180 mg/dL When Given to Drug-naïve, Diabetic Subjects From Baseline to Week 16 |
|---|---|
| Description | |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 85 | 89 |
| Baseline to 16 Weeks |
41.2
29.2%
|
41.6
28.7%
|
| Baseline to 16 Weeks LOCF: Pla N=95, Met N=97 |
37.9
26.9%
|
41.2
28.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8804 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.21 | |
| Confidence Interval |
(2-Sided) 95% 0.63 to 2.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5525 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.38 | |
| Confidence Interval |
(2-Sided) 95% 0.73 to 2.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5648 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3170 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Title | Percent of Subjects Achieving Hs-C-Reactive Protein Goal of <2.0 mg/L When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. The treatment duration was 16 weeks. |
| Measure Participants | 78 | 82 |
| Baseline to 16 Weeks |
21.8
15.5%
|
22.0
15.2%
|
| Baseline to 16 Weeks LOCF: Pla N=91, Met N=90 |
19.8
14%
|
20.0
13.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9008 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.64 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 4.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9035 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.40 | |
| Confidence Interval |
(2-Sided) 95% 0.60 to 3.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2874 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4344 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Title | Percent Change in Low Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed=the full analysis set (FAS). The FAS included randomized subjects who took at least 1 dose of randomized medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The total treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg once daily. The total treatment duration was 16 weeks. |
| Measure Participants | 98 | 98 |
| Baseline to 8 Weeks |
1.74
(1.888)
|
-17.88
(1.921)
|
| Baseline to 16 Weeks: Pla N=92, Col N=95 |
2.39
(2.191)
|
-15.08
(2.209)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -19.62 | |
| Confidence Interval |
(2-Sided) 95% -24.61 to -14.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -17.47 | |
| Confidence Interval |
(2-Sided) 95% -23.24 to -11.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change in Non-High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 98 | 98 |
| Baseline to 8 Weeks |
1.50
(1.433)
|
-10.98
(1.461)
|
| Baseline to 16 Weeks: Pla N=92, Col N=95 |
1.20
(1.850)
|
-9.08
(1.867)
|
| Baseline to 16 Weeks LOCF: Pla N=104, Col N=103 |
0.69
(1.739)
|
-8.37
(1.770)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -12.47 | |
| Confidence Interval |
(2-Sided) 95% -16.26 to -8.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -10.28 | |
| Confidence Interval |
(2-Sided) 95% -15.15 to -5.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -9.06 | |
| Confidence Interval |
(2-Sided) 95% -13.69 to -4.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change in High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 98 | 98 |
| Baseline to 8 Weeks |
-1.12
(1.398)
|
2.85
(1.433)
|
| Baseline to 16 Weeks: Pla N=92, Col N=95 |
4.42
(1.580)
|
3.57
(1.601)
|
| Baseline to 16 Weeks LOCF: Pla N=104, Col N=103 |
4.06
(1.447)
|
3.56
(1.481)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0357 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.96 | |
| Confidence Interval |
(2-Sided) 95% 0.27 to 7.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6878 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.85 | |
| Confidence Interval |
(2-Sided) 95% -5.01 to 3.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7972 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.50 | |
| Confidence Interval |
(2-Sided) 95% -4.37 to 3.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change in Total Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 99 | 98 |
| Baseline to 8 Weeks |
0.77
(1.169)
|
-8.15
(1.206)
|
| Baseline to 16 Weeks: Pla N=92, Col N=95 |
1.66
(1.519)
|
-6.59
(1.536)
|
| Baseline to 16 Weeks: Pla N=104, Col N=103 |
1.22
(1.422)
|
-6.01
(1.452)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.91 | |
| Confidence Interval |
(2-Sided) 95% -12.02 to -5.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.26 | |
| Confidence Interval |
(2-Sided) 95% -12.25 to -4.26 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.23 | |
| Confidence Interval |
(2-Sided) 95% -11.03 to -3.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change in Apolipoprotein A-1 in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 96 | 95 |
| Baseline to 8 Weeks |
-.032
(1.150)
|
3.18
(1.190)
|
| Baseline to 16 Weeks: Pla N=89, Col N=94 |
3.53
(1.312)
|
5.67
(1.323)
|
| Baseline to 16 Weeks LOCF: Pla N=102, Col N=102 |
3.68
(1.205)
|
5.46
(1.232)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0257 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.50 | |
| Confidence Interval |
(2-Sided) 95% 0.43 to 6.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2238 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.13 | |
| Confidence Interval |
(2-Sided) 95% -1.32 to 5.58 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2763 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.78 | |
| Confidence Interval |
(2-Sided) 95% -1.44 to 4.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change in Apolipoprotein B in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 96 | 95 |
| Baseline to 8 Weeks |
1.22
(1.435)
|
-8.62
(1.487)
|
| Baseline to 16 Weeks: Pla N=89, Col N=94 |
0.67
(1.788)
|
-8.00
(1.807)
|
| Baseline to 16 Weeks LOCF: Pla N=102, Col N=102 |
0.57
(1.648)
|
-7.52
(1.685)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -9.83 | |
| Confidence Interval |
(2-Sided) 95% -13.68 to -5.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.67 | |
| Confidence Interval |
(2-Sided) 95% -13.40 to -3.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.09 | |
| Confidence Interval |
(2-Sided) 95% -12.50 to -3.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change in Apolipoprotein CIII in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 94 | 95 |
| Baseline to 8 Weeks |
3.91
(3.301)
|
17.71
(3.043)
|
| Baseline to 16 Weeks: Pla N=88, Col N=91 |
9.31
(5.126)
|
20.89
(5.231)
|
| Baseline to 16 Weeks: Pla N=100, Col N=102 |
9.38
(4.627)
|
19.83
(4.611)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 13.80 | |
| Confidence Interval |
(2-Sided) 95% 5.87 to 21.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0901 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 11.58 | |
| Confidence Interval |
(2-Sided) 95% -1.83 to 24.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0918 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 10.45 | |
| Confidence Interval |
(2-Sided) 95% -1.71 to 22.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change in Triglycerides in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 99 | 98 |
| Baseline to 8 Weeks |
0.00
|
16.57
|
| Baseline to 16 Weeks: Pla N=92, Col N=95 |
-4.61
|
5.91
|
| Baseline to 16 Weeks: Pla N=104, Col N=103 |
-4.35
|
5.91
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | P-Value is from the non-parametric ANCOVA stratified by country | |
| Method | ANCOVA | |
| Comments | Non-parametric | |
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | 15.78 | |
| Confidence Interval |
(2-Sided) 95% 6.27 to 25.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The median difference was calculated using Hodges-Lehmann point estimates and corresponding 95% confidence interval was constructed using the method of Moses. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0011 |
| Comments | P-Value is from the non-parametric ANCOVA stratified by country | |
| Method | ANCOVA | |
| Comments | Non-parametric | |
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | 16.07 | |
| Confidence Interval |
(2-Sided) 95% 6.33 to 26.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The median difference was calculated using Hodges-Lehmann point estimates and corresponding 95% confidence interval was constructed using the method of Moses. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | P-Value is from the non-parametric ANCOVA stratified by country | |
| Method | ANCOVA | |
| Comments | Non-parametric | |
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | 14.33 | |
| Confidence Interval |
(2-Sided) 95% 5.11 to 23.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The median difference was calculated using Hodges-Lehmann point estimates and corresponding 95% confidence interval was constructed using the method of Moses. | |
| Title | Percent Change in Hs-C-Reactive Protein in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 92 | 95 |
| Baseline to 16 Weeks |
-11.04
|
-13.43
|
| Baseline to16 LOCF: Pla N=102, Col N=101 |
-10.24
|
-14.12
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6523 |
| Comments | P-Value was from the non-parametric ANCOVA stratified by country | |
| Method | ANCOVA | |
| Comments | Non-parametric | |
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | -3.29 | |
| Confidence Interval |
(2-Sided) 95% -17.50 to 10.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The median difference was calculated using Hodges-Lehmann point estimates and corresponding 95% confidence interval was constructed using the method of Moses. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3934 |
| Comments | P-Value was from the non-parametric ANCOVA stratified by country | |
| Method | ANCOVA | |
| Comments | Non-parametric | |
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | -4.38 | |
| Confidence Interval |
(2-Sided) 95% -17.51 to 8.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The median difference was calculated using Hodges-Lehmann point estimates and corresponding 95% confidence interval was constructed using the method of Moses. | |
| Title | Level of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. These 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam | Pre-Diabetes Group: Placebo (LOCF) | Pre-Diabetes Group: Colesevelam (LOCF) |
|---|---|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 89 | 93 | 99 | 99 |
| Total Very Low Density Lipoprotein (VLDL) Particle |
1.83
(3.363)
|
1.92
(3.337)
|
0.72
(3.132)
|
2.25
(3.149)
|
| Large VLDL Chylomicron Particles |
-.80
(0.459)
|
1.64
(0.453)
|
-0.86
(0.424)
|
1.53
(0.426)
|
| Medium VLDL Particles |
1.56
(2.004)
|
6.59
(1.986)
|
1.15
(1.890)
|
6.40
(1.895)
|
| Small VLDL Particles |
1.15
(1.967)
|
-6.34
(1.951)
|
0.52
(1.837)
|
-5.73
(1.844)
|
| Total Low Density Lipoprotein (LDL) Particles |
-24.7
(38.15)
|
-135.2
(37.83)
|
-25.7
(35.97)
|
-138.4
(36.15)
|
| Intermediate Density Lipoprotein (LDL) Particles |
-14.9
(5.71)
|
-15.3
(5.69)
|
-14.7
(5.37)
|
-17.0
(5.41)
|
| Large LDL Particles |
91.3
(29.20)
|
27.6
(28.99)
|
91.3
(26.79)
|
27.5
(26.93)
|
| Small LDL Particles |
-110.9
(44.15)
|
-148.6
(43.79)
|
-102.5
(41.72)
|
-149.4
(41.94)
|
| Medium Small LDL Particles |
-22.5
(9.02)
|
-28.2
(8.95)
|
-21.5
(8.48)
|
-28.3
(8.52)
|
| Very Small LDL Particles |
-78.3
(35.60)
|
-120.3
(35.32)
|
-81.0
(33.68)
|
-121.0
(33.86)
|
| Total High Density Lipoprotein (HDL) Particles |
0.30
(0.456)
|
0.28
(0.452)
|
0.38
(0.428)
|
0.28
(0.430)
|
| Large HDL Particles |
0.51
(0.211)
|
1.09
(0.210)
|
0.53
(0.197)
|
1.10
(0.198)
|
| Medium HDL Particles |
-0.23
(0.335)
|
-0.03
(0.334)
|
-0.24
(0.310)
|
-0.05
(0.312)
|
| Small HDL Particles |
0.04
(0.475)
|
-0.77
(0.471)
|
0.10
(0.450)
|
-0.75
(0.453)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Total VLDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9838 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 95% -8.66 to 8.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Total VLDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7157 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.53 | |
| Confidence Interval |
(2-Sided) 95% -6.73 to 9.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Large VLDL Chylomicron Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.44 | |
| Confidence Interval |
(2-Sided) 95% 1.25 to 3.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Large VLDL Chylomicron Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.39 | |
| Confidence Interval |
(2-Sided) 95% 1.27 to 3.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Medium VLDL Chylomicron Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0577 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.04 | |
| Confidence Interval |
(2-Sided) 95% -0.17 to 10.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Medium VLDL Chylomicron Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0390 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.24 | |
| Confidence Interval |
(2-Sided) 95% 0.27 to 10.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Small VLDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0044 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.49 | |
| Confidence Interval |
(2-Sided) 95% -12.61 to -2.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Small VLDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0118 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.24 | |
| Confidence Interval |
(2-Sided) 95% -11.09 to -1.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Total Low Density Lipoprotein (LDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0293 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -110.6 | |
| Confidence Interval |
(2-Sided) 95% -209.9 to -11.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Total Low Density Lipoprotein (LDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0202 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -112.7 | |
| Confidence Interval |
(2-Sided) 95% -207.6 to -17.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Intermediate Density Lipoprotein (LDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9629 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -15.2 to 14.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Intermediate Density Lipoprotein (LDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7485 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.3 | |
| Confidence Interval |
(2-Sided) 95% -16.5 to 11.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Large LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1007 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -63.6 | |
| Confidence Interval |
(2-Sided) 95% -139.7 to 12.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Large LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0768 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -63.8 | |
| Confidence Interval |
(2-Sided) 95% -134.6 to 6.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4143 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -47.7 | |
| Confidence Interval |
(2-Sided) 95% -162.7 to 67.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4020 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -46.9 | |
| Confidence Interval |
(2-Sided) 95% -157.1 to 63.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Medium Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6378 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.6 | |
| Confidence Interval |
(2-Sided) 95% -29.1 to 17.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Medium Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5528 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.7 | |
| Confidence Interval |
(2-Sided) 95% -29.1 to 15.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Very Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3730 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -42.0 | |
| Confidence Interval |
(2-Sided) 95% -134.8 to 50.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Very Small LDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3764 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -40.0 | |
| Confidence Interval |
(2-Sided) 95% -129.0 to 49.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Total High Density Lipoprotein (HDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9807 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.01 | |
| Confidence Interval |
(2-Sided) 95% -1.20 to 1.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Total High Density Lipoprotein (HDL) Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8615 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.10 | |
| Confidence Interval |
(2-Sided) 95% -1.23 to 1.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Large HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0364 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.59 | |
| Confidence Interval |
(2-Sided) 95% 0.04 to 1.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Large HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0340 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.56 | |
| Confidence Interval |
(2-Sided) 95% 0.04 to 1.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Medium HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6587 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.20 | |
| Confidence Interval |
(2-Sided) 95% -0.68 to 1.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Medium HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6554 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.19 | |
| Confidence Interval |
(2-Sided) 95% -0.63 to 1.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Small HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1957 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.82 | |
| Confidence Interval |
(2-Sided) 95% -2.06 to 0.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Small HDL Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1622 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.85 | |
| Confidence Interval |
(2-Sided) 95% -2.03 to 0.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Particle Size of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam | Pre-Diabetes Group: Placebo (LOCF) | Pre-Diabetes Group: Colesevelam (LOCF) |
|---|---|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 89 | 93 | 99 | 99 |
| Very Low Density Lipoprotein Particles |
-1.85
(0.956)
|
4.15
(0.948)
|
-1.43
(0.877)
|
3.89
(0.883)
|
| Low Density Lipoprotein Particles |
.23
(0.068)
|
0.11
(0.068)
|
0.23
(0.064)
|
0.12
(0.065)
|
| High Density Lipoprotein Particles |
0.06
(0.026)
|
0.15
(0.026)
|
0.05
(0.024)
|
0.15
(0.024)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Very Low Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.99 | |
| Confidence Interval |
(2-Sided) 95% 3.51 to 8.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Very Low Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.31 | |
| Confidence Interval |
(2-Sided) 95% 3.00 to 7.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Low Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1742 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.30 to 0.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Low Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1870 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.11 | |
| Confidence Interval |
(2-Sided) 95% -0.28 to 0.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | High Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0063 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 95% 0.03 to 0.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | High Density Lipoprotein Particles | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0020 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.10 | |
| Confidence Interval |
(2-Sided) 95% 0.04 to 0.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change of Various Calculated Lipid Parameters in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary. |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam | Pre-Diabetes Group: Placebo (LOCF) | Pre-Diabetes Group: Colesevelam (LOCF) |
|---|---|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 89 | 93 | 99 | 99 |
| Changes in Calculated Total Triglycerides |
-5.0
(5.97)
|
19.4
(5.91)
|
-6.4
(5.60)
|
18.0
(5.62)
|
| Changes: Calculated Very Low Density Triglycerides |
-4.6
(5.70)
|
21.7
(5.64)
|
-5.9
(5.34)
|
20.6
(5.36)
|
| Changes in Calculated High Density Lipoprotein -C |
1.4
(0.75)
|
2.9
(0.74)
|
1.4
(0.69)
|
2.9
(0.69)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Changes in Calculated Total Triglycerides | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0022 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 24.4 | |
| Confidence Interval |
(2-Sided) 95% 8.9 to 39.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Changes in Calculated Total Triglycerides | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0013 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 24.3 | |
| Confidence Interval |
(2-Sided) 95% 9.6 to 39.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Changes: Calculated Very Low Density Triglycerides | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0006 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 26.3 | |
| Confidence Interval |
(2-Sided) 95% 11.5 to 41.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Changes: Calculated Very Low Density Triglycerides | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 26.5 | |
| Confidence Interval |
(2-Sided) 95% 12.5 to 40.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin |
|---|---|---|
| Comments | Changes in Calculated High Density Lipoprotein-Cholesterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1257 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.5 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 3.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group: Placebo + Metformin for 16 Weeks (LOCF), Type 2 Diabetes Group:Colesevelam+Metformin for 16 Weeks(LOCF) |
|---|---|---|
| Comments | Changes in Calculated High Density Lipoprotein-Cholesterol | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1054 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.5 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 3.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of HbA1c in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 100 | 96 |
| Baseline to 4 weeks |
-0.06
(0.026)
|
-0.09
(0.028)
|
| Baseline to 8 weeks: Pla N=98, Col N=96 |
-0.06
(0.026)
|
-0.10
(0.026)
|
| Baseline to 12 weeks: Pla N=94, Col N=94 |
-0.05
(0.026)
|
-0.11
(0.027)
|
| Baseline to 16 weeks: Pla N=90, Col N=95 |
-0.03
(0.034)
|
-0.11
(0.034)
|
| Baseline to 16 weeks LOCF: Pla N=106, Col N=103 |
-0.03
(0.030)
|
-0.12
(0.031)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 4 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2971 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.11 to 0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2567 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.11 to 0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1081 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.13 to 0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0790 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.17 to 0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0206 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.10 | |
| Confidence Interval |
(2-Sided) 95% -0.18 to -0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Fasting Plasma Glucose in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12, and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 101 | 97 |
| Baseline to 4 weeks |
0.7
(0.95)
|
-3.5
(0.97)
|
| Baseline to 8 weeks: Pla N=97, Col N=97 |
-1.1
(0.94)
|
-3.1
(0.95)
|
| Baseline to 12 weeks: Pla N=95, Col N=95 |
0.4
(1.11)
|
-2.4
(1.13)
|
| Baseline to 16 weeks: Pla N=91, Col N=95 |
-0.5
(1.87)
|
-2.8
(1.86)
|
| Baseline to 16 weeks LOCF: Pla N=106, Col N=103 |
-0.5
(1.65)
|
-3.1
(1.67)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 4 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -4.3 | |
| Confidence Interval |
(2-Sided) 95% -6.8 to -1.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1184 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 95% -4.5 to 0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0615 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.8 | |
| Confidence Interval |
(2-Sided) 95% -5.8 to 0.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3617 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.3 | |
| Confidence Interval |
(2-Sided) 95% -7.2 to 2.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2372 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.6 | |
| Confidence Interval |
(2-Sided) 95% -7.0 to 1.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change of Fasting Insulin in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 95 | 93 |
| Baseline to 4 Weeks |
-1.269
(0.6651)
|
-0.348
(0.6769)
|
| Baseline to 8 Weeks: Pla N=94, Col N=97 |
-1.208
(0.4377)
|
-0.513
(0.4377)
|
| Baseline to 12 Weeks: Pla N=93, Col N=93 |
-0.848
(0.4371)
|
-2.066
(0.4463)
|
| Baseline to 16 Weeks: Pla N=90, Col N=94 |
-0.063
(1.2082)
|
-0.497
(1.1980)
|
| Baseline to 16 Weeks LOCF: Pla N=105, Col N=102 |
-0.019
(1.0597)
|
-0.512
(1.0770)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin |
|---|---|---|
| Comments | Baseline to 4 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2982 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.921 | |
| Confidence Interval |
(2-Sided) 95% -0.821 to 2.663 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2361 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.695 | |
| Confidence Interval |
(2-Sided) 95% -0.458 to 1.848 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0413 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.218 | |
| Confidence Interval |
(2-Sided) 95% -2.388 to -0.049 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7858 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.434 | |
| Confidence Interval |
(2-Sided) 95% -3.583 to 2.715 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7314 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.493 | |
| Confidence Interval |
(2-Sided) 95% -3.321 to 2.335 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change of Fasting C-peptide Levels in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 91 | 94 |
| Baseline to 16 Weeks |
0.039
(0.1124)
|
-0.050
(0.1132)
|
| Baseline to 16 Weeks LOCF: Pla N=101, Col N=100 |
0.049
(0.1041)
|
-0.057
(0.1059)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5530 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.089 | |
| Confidence Interval |
(2-Sided) 95% -0.385 to 0.207 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4554 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.105 | |
| Confidence Interval |
(2-Sided) 95% -0.383 to 0.172 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change of Glucose Levels 30 Minutes Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 88 | 94 |
| Baseline to 16 Weeks |
-0.9
(3.82)
|
-1.8
(3.71)
|
| Baseline to 16 Weeks LOCF: Pla N=96, Col N=97 |
-1.3
(3.60)
|
-2.5
(3.58)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8583 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -10.7 to 8.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7975 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -10.5 to 8.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change of Glucose Levels 1 Hour Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 85 | 95 |
| Baseline to 16 Weeks |
-1.0
(4.51)
|
-8.0
(4.33)
|
| Baseline to 16 Weeks LOCF: Pla N=93, Col N=98 |
-0.4
(4.28)
|
-8.6
(4.19)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2330 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.0 | |
| Confidence Interval |
() 95% -18.5 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1412 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.2 | |
| Confidence Interval |
(2-Sided) 95% -19.2 to 2.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change of Glucose Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 90 | 95 |
| Baseline to 16 Weeks |
-4.9
(4.65)
|
-6.3
(4.65)
|
| Baseline to 16 Weeks LOCF: Pla N=98, Col N=98 |
-4.2
(4.40)
|
-6.1
(4.46)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8192 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.4 | |
| Confidence Interval |
(2-Sided) 95% -13.7 to 10.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7513 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.9 | |
| Confidence Interval |
(2-Sided) 95% -13.5 to 9.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change of Insulin Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 84 | 91 |
| Baseline to 16 Weeks |
-8.563
(6.6122)
|
-15.472
(6.4814)
|
| Baseline to 16 Weeks LOCF: Pla N=92, Col N=94 |
-9.784
(6.2865)
|
-14.954
(6.2745)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4301 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.910 | |
| Confidence Interval |
(2-Sided) 95% -24.156 to 10.336 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5369 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.170 | |
| Confidence Interval |
(2-Sided) 95% -21.661 to 11.321 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change of C-Peptide Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 85 | 93 |
| Baseline to 16 Weeks |
-0.447
(0.3527)
|
-0.598
(0.3449)
|
| Baseline to 16 Weeks LOCF: Pla N=93, Col N=96 |
-0.581
(0.3374)
|
-0.551
(0.3359)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7447 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.151 | |
| Confidence Interval |
(2-Sided) 95% -1.068 to 0.765 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9476 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.029 | |
| Confidence Interval |
(2-Sided) 95% -0.853 to 0.911 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 94 | 89 |
| Baseline to 8 Weeks |
6.4
4.5%
|
29.2
20.1%
|
| Baseline to 16 Weeks: Pla N=88, Col N=86 |
10.2
7.2%
|
29.1
20.1%
|
| Baseline to 16 Weeks LOCF: Pla N=100, Col N=94 |
11.0
7.8%
|
28.7
19.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0018 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 5.23 | |
| Confidence Interval |
(2-Sided) 95% 2.06 to 13.58 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0019 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 4.46 | |
| Confidence Interval |
(2-Sided) 95% 1.89 to 10.54 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Title | Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <70 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects |
|---|---|
| Description | |
| Time Frame | Baseline to 8, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 98 | 98 |
| Baseline to 8 Weeks |
2.0
1.4%
|
11.2
7.7%
|
| Baseline to 16 Weeks: Pla N=92, Col N=95 |
3.3
2.3%
|
7.4
5.1%
|
| Baseline to 16 Weeks LOCF: Pla N=104, Col N=103 |
2.9
2.1%
|
6.8
4.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0104 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2224 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.22 | |
| Confidence Interval |
(2-Sided) 95% 0.53 to 9.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1990 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.21 | |
| Confidence Interval |
(2-Sided) 95% 0.53 to 9.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2778 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2785 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Title | Change in Body Weight in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 92 | 96 |
| Baseline to 16 Weeks |
-2.56
(0.823)
|
-3.24
(0.832)
|
| Baseline to 16 Weeks LOCF: Pla N=103, Col N=101 |
-2.63
(0.758)
|
-3.25
(0.779)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5353 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.68 | |
| Confidence Interval |
(2-Sided) 95% -2.84 to 1.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5475 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.62 | |
| Confidence Interval |
(2-Sided) 95% -2.64 to 1.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Waist-to-Hip Ratio in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 92 | 96 |
| Baseline to 16 Weeks |
0.0059
(0.00477)
|
-0.0058
(0.00480)
|
| Baseline to 16 Weeks: Pla N=103, Col N=101 |
0.0051
(0.00437)
|
-0.0061
(0.00447)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0678 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.0116 | |
| Confidence Interval |
(2-Sided) 95% -0.0241 to 0.0009 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0585 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.0112 | |
| Confidence Interval |
(2-Sided) 95% -0.0228 to 0.0004 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Curve for Plasma Glucose From 0 to 120 Minutes During the Oral Glucose Tolerance Tests in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 84 | 93 |
| Baseline to 16 Weeks |
-5.26
(6.109)
|
-8.27
(5.878)
|
| Baseline to 16 Weeks: Pla N=92, Col N=96 |
-4.40
(5.791)
|
-9.20
(5.685)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7051 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -3.00 | |
| Confidence Interval |
(2-Sided) 95% -18.64 to 12.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5267 |
| Comments | P-Value is for the LS Mean Difference between treatment groups | |
| Method | ANCOVA | |
| Comments | The ANCOVA model includes treatment and country as fixed effects and baseline lab value as a covariate | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -4.80 | |
| Confidence Interval |
(2-Sided) 95% -19.72 to 10.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Achievement of <140 mg/dL Plasma Glucose 2 Hours Post the Oral Glucose Tolerance Test in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was >or= to 140 mg/dL From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 57 | 67 |
| Baseline to 16 Weeks |
42.1
29.9%
|
37.3
25.7%
|
| Baseline to 16 Weeks LOCF: Pla N=61, Col N=69 |
41.0
29.1%
|
37.7
26%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5882 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 95% 0.40 to 1.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7098 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.93 | |
| Confidence Interval |
(2-Sided) 95% 0.44 to 1.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6835 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8461 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Title | Percent Achievement of <110 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 110 mg/dL From Baseline to 4, 8, 12, and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12, and 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 34 | 26 |
| Baseline to 4 Weeks |
38.2
27.1%
|
57.7
39.8%
|
| Baseline to 8 Weeks: Pla N=34, Col N=26 |
50.0
35.5%
|
42.3
29.2%
|
| Baseline to 12 Weeks: Pla N=34, Col N=26 |
55.9
39.6%
|
53.8
37.1%
|
| Baseline to 16 Weeks: Pla N=32, Col N=25 |
56.3
39.9%
|
44.0
30.3%
|
| Baseline to 16 Weeks LOCF: Pla N=36, Col N=29 |
55.6
39.4%
|
48.3
33.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 4 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2079 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4053 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5752 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7994 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.84 | |
| Confidence Interval |
(2-Sided) 95% 0.25 to 2.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9960 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.98 | |
| Confidence Interval |
(2-Sided) 95% 0.32 to 3.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7783 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9774 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Title | Percent Achievement of <100 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 100 mg/dL From Baseline to 4, 8, 12 and 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 4, 8, 12 and 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 69 | 63 |
| Baseline to 4 Weeks |
7.2
5.1%
|
39.7
27.4%
|
| Baseline to 8 Weeks: Pla N=68, Col N=64 |
22.1
15.7%
|
29.7
20.5%
|
| Baseline to 12 Weeks: Pla N=66, Col N=65 |
16.7
11.8%
|
33.8
23.3%
|
| Baseline to 16 Weeks: Pla N=62, Col N=64 |
27.4
19.4%
|
40.6
28%
|
| Baseline to 16 Weeks LOCF: Pla N=73, Col N=68 |
23.3
16.5%
|
39.7
27.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 4 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 8 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4058 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 12 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0254 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1499 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.62 | |
| Confidence Interval |
(2-Sided) 95% 0.74 to 3.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0420 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.08 | |
| Confidence Interval |
(2-Sided) 95% 0.97 to 4.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2240 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0593 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Title | Percent Achievement of <140 mg/dL Plasma Glucose Post 2 Hour Glucose Tolerance Test and Fasting Plasma Glucose <110 mg/dL in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 65 | 72 |
| Baseline to 16 Weeks |
36.9
26.2%
|
30.6
21.1%
|
| Baseline to 16 Weeks LOCF: Pla N=69, Col N=75 |
36.2
25.7%
|
32.0
22.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4794 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.66 | |
| Confidence Interval |
(2-Sided) 95% 0.31 to 1.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6667 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.75 | |
| Confidence Interval |
(2-Sided) 95% 0.37 to 1.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2768 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4395 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Title | Percent Achievement of Hs-C-Reactive Protein <2.0 mg/L in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 2.0 mg/L From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 69 | 60 |
| Baseline to 16 Weeks |
13.0
9.2%
|
21.7
15%
|
| Baseline to 16 Weeks LOCF: Pla N=78, Col N=65 |
12.8
9.1%
|
20.8
14.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1375 |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.43 | |
| Confidence Interval |
(2-Sided) 95% 0.89 to 6.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1996 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | P-Value for comparing percentages was from the Cochran-Mantel-Haenszel test stratified by country. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.22 | |
| Confidence Interval |
(2-Sided) 95% 0.85 to 5.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0829 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Type 2 Diabetes Group:Placebo+Metformin, Type 2 Diabetes Group:Colesevelam+Metformin |
|---|---|---|
| Comments | Baseline to 16 Weeks LOCF | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1037 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Contained treatment and country as factors and baseline lab value as a covariate | |
| Title | Percent of Subjects Meeting Type 2 Diabetes Criteria (Fasting Plasma Glucose >or= to 126 mg/dL or Plasma Glucose >or= to 200 mg/dL Post 2 Hr Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline to 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The No. analyzed equals the full analysis set (FAS). The FAS included all randomized subjects who took at least 1 dose of randomized study medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. The 16 week analyses are both LOCF and no LOCF. |
| Arm/Group Title | Pre-Diabetes Group: Placebo | Pre-Diabetes Group: Colesevelam |
|---|---|---|
| Arm/Group Description | This group received 6 matching colesevelam placebo tablets/day. The treatment duration was 16 weeks. | This group received 6 colesevelam tablets 625 mg/day. The treatment duration was 16 weeks. |
| Measure Participants | 79 | 81 |
| Baseline to 16 Weeks |
10.1
7.2%
|
11.1
7.7%
|
| Baseline to 16 Weeks LOCF: Pla N=87, Col N=84 |
10.3
7.3%
|
10.7
7.4%
|
Adverse Events
| Time Frame | Adverse events were collected from the signing of the informed consent form until the end of the study + a follow up period (until the AE resolved or stabilized). This period of time equals about 17.5 weeks. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AEs were noted by investigator or reported by subject. Nature, duration, remedial action, and severity of AE were recorded. Lab abnormalities were AEs if they needed intervention, further investigation, led to a change in medication, or were part of a larger disease process. Only 107 in the prediabetes colesevelam group because 1 did not take drug. | |||||||
| Arm/Group Title | Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin | Pre-diabetic Group: Placebo | Pre-diabetic Group: Colesevelam | ||||
| Arm/Group Description | This group received 6 matching colesevalm placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. This treatment duration was 16 weeks. | This group received 6 colevevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. This treatment duration was 16 weeks. | This group was given 6 placebo tablets once a day. They matched the colesevelam tablets. This treatment duration was 16 weeks. | This group was given 6 colesevelam tablets, 625mg, once a day. This treatment duration was 16 weeks. | ||||
All Cause Mortality |
||||||||
| Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin | Pre-diabetic Group: Placebo | Pre-diabetic Group: Colesevelam | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin | Pre-diabetic Group: Placebo | Pre-diabetic Group: Colesevelam | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/141 (0.7%) | 2/145 (1.4%) | 2/108 (1.9%) | 2/107 (1.9%) | ||||
| Cardiac disorders | ||||||||
| Coronary artery stenosis | 1/141 (0.7%) | 0/145 (0%) | 0/108 (0%) | 0/107 (0%) | ||||
| General disorders | ||||||||
| Chest pain | 0/141 (0%) | 1/145 (0.7%) | 0/108 (0%) | 0/107 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholelithiasis | 0/141 (0%) | 0/145 (0%) | 1/108 (0.9%) | 0/107 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Lung squamous cell carcinoma | 0/141 (0%) | 1/145 (0.7%) | 0/108 (0%) | 0/107 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Cystocele | 0/141 (0%) | 0/145 (0%) | 1/108 (0.9%) | 0/107 (0%) | ||||
| Erectile dysfunction | 0/141 (0%) | 0/145 (0%) | 0/108 (0%) | 1/107 (0.9%) | ||||
| Polycystic Ovaries | 0/141 (0%) | 0/145 (0%) | 0/108 (0%) | 1/107 (0.9%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Type 2 Diabetes Group: Placebo + Metformin | Type 2 Diabetes Group: Colesevelam + Metformin | Pre-diabetic Group: Placebo | Pre-diabetic Group: Colesevelam | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 97/141 (68.8%) | 97/141 (68.8%) | 63/108 (58.3%) | 57/107 (53.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 5/141 (3.5%) | 4/141 (2.8%) | 0/108 (0%) | 0/107 (0%) | ||||
| Abdominal Pain | 8/141 (5.7%) | 6/141 (4.3%) | 3/108 (2.8%) | 3/107 (2.8%) | ||||
| Abdominal pain uppper | 3/141 (2.1%) | 5/141 (3.5%) | 0/108 (0%) | 0/107 (0%) | ||||
| Constipation | 2/141 (1.4%) | 6/141 (4.3%) | 5/108 (4.6%) | 10/107 (9.3%) | ||||
| Dyspepsia | 5/141 (3.5%) | 5/141 (3.5%) | 0/108 (0%) | 3/107 (2.8%) | ||||
| Flatulence | 4/141 (2.8%) | 3/141 (2.1%) | 0/108 (0%) | 0/107 (0%) | ||||
| Gastritis | 3/141 (2.1%) | 7/141 (5%) | 2/108 (1.9%) | 4/107 (3.7%) | ||||
| Nausea | 11/141 (7.8%) | 18/141 (12.8%) | 0/108 (0%) | 3/107 (2.8%) | ||||
| Toothache | 0/141 (0%) | 0/141 (0%) | 3/108 (2.8%) | 1/107 (0.9%) | ||||
| Vomiting | 2/141 (1.4%) | 6/141 (4.3%) | 0/108 (0%) | 3/107 (2.8%) | ||||
| General disorders | ||||||||
| Asthenia | 4/141 (2.8%) | 5/141 (3.5%) | 0/108 (0%) | 0/107 (0%) | ||||
| Pyrexia | 7/141 (5%) | 2/141 (1.4%) | 1/108 (0.9%) | 3/107 (2.8%) | ||||
| Infections and infestations | ||||||||
| Gastroenteritis | 3/141 (2.1%) | 2/141 (1.4%) | 0/108 (0%) | 0/107 (0%) | ||||
| Influenza | 9/141 (6.4%) | 12/141 (8.5%) | 7/108 (6.5%) | 9/107 (8.4%) | ||||
| Nasopharyngitis | 2/141 (1.4%) | 5/141 (3.5%) | 5/108 (4.6%) | 1/107 (0.9%) | ||||
| Sinusitis | 3/141 (2.1%) | 3/141 (2.1%) | 1/108 (0.9%) | 3/107 (2.8%) | ||||
| Upper Respiratory Tract Infection | 6/141 (4.3%) | 3/141 (2.1%) | 3/108 (2.8%) | 1/107 (0.9%) | ||||
| Urinary tract infection | 7/141 (5%) | 3/141 (2.1%) | 3/108 (2.8%) | 1/107 (0.9%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 4/141 (2.8%) | 1/141 (0.7%) | 0/108 (0%) | 0/107 (0%) | ||||
| Dyslipidemia | 4/141 (2.8%) | 5/141 (3.5%) | 0/108 (0%) | 0/107 (0%) | ||||
| Hypoglycemia | 3/141 (2.1%) | 2/141 (1.4%) | 0/108 (0%) | 0/107 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 2/141 (1.4%) | 5/141 (3.5%) | 2/108 (1.9%) | 3/107 (2.8%) | ||||
| Back pain | 8/141 (5.7%) | 0/141 (0%) | 10/108 (9.3%) | 3/107 (2.8%) | ||||
| Muscle spasms | 4/141 (2.8%) | 3/141 (2.1%) | 0/108 (0%) | 0/107 (0%) | ||||
| Musculoskeletal pain | 2/141 (1.4%) | 3/141 (2.1%) | 0/108 (0%) | 0/107 (0%) | ||||
| Myalgia | 1/141 (0.7%) | 4/141 (2.8%) | 0/108 (0%) | 0/107 (0%) | ||||
| Pain in extremity | 5/141 (3.5%) | 5/141 (3.5%) | 2/108 (1.9%) | 4/107 (3.7%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 5/141 (3.5%) | 9/141 (6.4%) | 0/108 (0%) | 5/107 (4.7%) | ||||
| Headache | 14/141 (9.9%) | 12/141 (8.5%) | 10/108 (9.3%) | 7/107 (6.5%) | ||||
| Somnolence | 3/141 (2.1%) | 2/141 (1.4%) | 0/108 (0%) | 0/107 (0%) | ||||
| Anxiety | 3/141 (2.1%) | 1/141 (0.7%) | 0/108 (0%) | 0/107 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 3/141 (2.1%) | 2/141 (1.4%) | 3/108 (2.8%) | 2/107 (1.9%) | ||||
| Pharyngolaryngeal pain | 1/141 (0.7%) | 4/141 (2.8%) | 0/108 (0%) | 0/107 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 8/141 (5.7%) | 2/141 (1.4%) | 5/108 (4.6%) | 2/107 (1.9%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The following language is employed: "If identified by DSI, any of DSI's confidential information as defined herein shall be deleted...Nothing in this publication section shall be taken as giving DSI and right of editorial control over any publication prepared by the Study Site."
Results Point of Contact
| Name/Title | John Raia, Senior Director Professional Affairs |
|---|---|
| Organization | Daiichi Sankyo, Inc. |
| Phone | (973) 944-2683 |
| jraia@dsi.com |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00570739
Other Study ID Numbers:
- WEL-411
- IND 68,466
First Posted:
Dec 11, 2007
Last Update Posted:
Jul 27, 2010
Last Verified:
Jul 1, 2010