Efficacy and Safety of Colesevelam in Pediatric Patients With Genetic High Cholesterol
Sponsor
Daiichi Sankyo, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00145574
Collaborator
(none)
194
25
3
25
7.8
0.3
Study Details
Study Description
Brief Summary
This study will evaluate the lipid-lowering effect and safety of colesevelam therapy administered to heterozygous familial pediatric patients 10 through 17 years of age who are on a stable dose of a pediatric-approved statin monotherapy (atorvastatin, lovastatin, simvastatin or pravastatin), or who are treatment naive to lipid-lowering therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
194 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Colesevelam HCl Administered to Pediatric Patients With Heterozygous Familial Hypercholesterolemia on a Stable Dose of Statins or Treatment Naive to Lipid-lowering Therapy
Study Start Date
:
Nov 1, 2005
Actual Primary Completion Date
:
Dec 1, 2007
Actual Study Completion Date
:
Dec 1, 2007
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: high dose colesevelam colesevelam HCl 3.750 g |
Drug: colesevelam HCl
Tablets
|
| Experimental: Low dose colesevelam Low dose colesevelam 1.875 g |
Drug: colesevelam HCl
Tablets
|
| Placebo Comparator: placebo placebo comparator |
Drug: placebo
Matching Tablets
|
Outcome Measures
Primary Outcome Measures
- Percent Change in Plasma Low Density Lipoprotein-cholesterol (LDL-C) From Day 1 (Study Baseline) to Week 8. [8 weeks (week 8 - day 1)]
Percent change in LDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline)to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.
Secondary Outcome Measures
- Percent Change in Plasma Total Cholesterol (TC) From Day 1 (Study Baseline) to Week 8. [8 weeks (week 8 - day 1)]
Percent change in total cholesterol (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.
- Percent Change in Plasma Triglycerides (TG) From Day 1 (Study Baseline) to Week 8. [8 weeks (week 8 - day 1)]
Percent change in triglycerides (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.
- Percent Change in Plasma High-density Lipoprotein-cholesterol (HDL-C) From Day 1 (Study Baseline) to Week 8. [8 weeks (week 8 - day 1)]
Percent change in HDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.
- Percent Change in Plasma Non-high Density Lipoprotein-cholesterol (Non-HDL-C) From Day 1 (Study Baseline) to Week 8. [8 weeks (week 8 - day 1)]
Percent change in non-HDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.
- Percent Change in Plasma Apolipoprotien A-I (Apo A-1) From Day 1 (Study Baseline) to Week 8. [8 weeks (week 8 - day 1)]
Percent change in Apolipoprotien A-I (Apo A-1) (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.
- Percent Change in Plasma Apolipoprotein B (Apo B) From Day 1 (Study Baseline) to Week 8. [8 weeks (week 8 - day 1)]
Percent change in Apo B (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.
- Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Study Baseline (Day 1) to Week 26. [26 weeks (week 26 - day 1)]
Percent change in low-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.
- Percent Change in Total Cholesterol From Study Baseline (Day 1) to Week 26. [26 weeks (week 26 - day 1)]
Percent change in total cholesterol (TC) from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.
- Percent Change in Triglycerides From Study Baseline (Day 1) to Week 26. [26 weeks (week 26 - day 1)]
Percent change in triglycerides from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.
- Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Study Baseline (Day 1) to Week 26. [26 weeks (week 26 - day 1)]
Percent change in high-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.
- Percent Change in Non-high-density Lipoprotein Cholesterol From Study Baseline (Day 1) to Week 26. [26 weeks (week 26 - day 1)]
Percent change in non-high-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.
- Percent Change in Apolipoprotein A-I From Study Baseline (Day 1) to Week 26. [26 weeks (week 26 - day 1)]
Percent change in apolipoprotein A-I from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.
- Percent Change in Apolipoprotein B From Study Baseline (Day 1) to Week 26. [26 weeks (week 26 - day 1)]
Percent change in apolipoprotein B from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.
Eligibility Criteria
Criteria
Ages Eligible for Study:
10 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female patients
-
Ages 10 to 17 years inclusive
-
Diagnosis of heterozygous familial hypercholesterolemia
-
On a stable dose of statin monotherapy or are treatment naive to lipid- lowering agents
-
On a low-cholesterol diet
Exclusion Criteria:
- Patients should not have serious concomitant conditions that could interfere with the analysis of the results or that could interfere with the well-being of the patients
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington | District of Columbia | United States | ||
| 2 | St. Louis | Missouri | United States | ||
| 3 | Bronx | New York | United States | ||
| 4 | New Hyde Park | New York | United States | ||
| 5 | New York | New York | United States | ||
| 6 | Cincinnati | Ohio | United States | ||
| 7 | Wexford | Pennsylvania | United States | ||
| 8 | Salt Lake City | Utah | United States | ||
| 9 | Camperdown NSW | Australia | |||
| 10 | Vienna | Austria | |||
| 11 | Vancouver | British Columbia | Canada | ||
| 12 | Toronto | Ontario | Canada | ||
| 13 | Chicoutimi | Quebec | Canada | ||
| 14 | Laval | Quebec | Canada | ||
| 15 | Stefoy | Quebec | Canada | ||
| 16 | Holon | Israel | |||
| 17 | Jerusalem | Israel | |||
| 18 | Kefer Saba | Israel | |||
| 19 | Tel-Hashomer | Israel | |||
| 20 | Amsterdam | Netherlands | |||
| 21 | Rotterdam | Netherlands | |||
| 22 | Oslo | Norway | |||
| 23 | Observatory | South Africa | |||
| 24 | Pretoria | South Africa | |||
| 25 | Tygerberg | South Africa |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00145574
Other Study ID Numbers:
- WEL-410
First Posted:
Sep 5, 2005
Last Update Posted:
Apr 15, 2010
Last Verified:
Apr 1, 2010
Keywords provided by ,
,
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study was conducted at 41 clinical sites; Australia (1 site), Austria (1 site), Canada (5 sites), Hungary (1 site), Israel (5 sites), New Zealand (1 site), Norway (2 sites), Slovakia (3 sites), South Africa (4 sites), Czech Republic (3 sites), Netherlands (2 sites), and USA (13 sites). Study initiated November 5, 2005 completed December 18, 2007. |
|---|---|
| Pre-assignment Detail | Period I Run-In (4 weeks): Period I was a single-blind stabilization period prior to randomization. All subjects received 6 placebo tablets daily. Objective was to evaluate dosing compliance and tolerability to the tablets prior to randomization. Subjects could be on stable pediatric approved statin regimen and low cholesterol diet for 6 weeks. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam |
|---|---|---|---|
| Arm/Group Description | Placebo similar to active | Low dose colesevelam 1.9 grams per day | High dose colesevelam 3.8 grams per day |
| Period Title: Double Blind | |||
| STARTED | 65 | 65 | 64 |
| COMPLETED | 64 | 60 | 62 |
| NOT COMPLETED | 1 | 5 | 2 |
| Period Title: Double Blind | |||
| STARTED | 0 | 0 | 184 |
| COMPLETED | 0 | 0 | 173 |
| NOT COMPLETED | 0 | 0 | 11 |
Baseline Characteristics
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam | Total |
|---|---|---|---|---|
| Arm/Group Description | Placebo similar to active | Low dose colesevelam 1.9 grams per day | High dose colesevelam 3.8 grams per day | Total of all reporting groups |
| Overall Participants | 65 | 65 | 64 | 194 |
| Age (Count of Participants) | ||||
| <=18 years |
65
100%
|
65
100%
|
64
100%
|
194
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
14.3
(1.74)
|
14.1
(2.19)
|
13.9
(2.0)
|
14.1
(1.98)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
21
32.3%
|
26
40%
|
24
37.5%
|
71
36.6%
|
| Male |
44
67.7%
|
39
60%
|
40
62.5%
|
123
63.4%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
16
24.6%
|
14
21.5%
|
15
23.4%
|
45
23.2%
|
| Canada |
7
10.8%
|
9
13.8%
|
7
10.9%
|
23
11.9%
|
| Austria |
0
0%
|
1
1.5%
|
0
0%
|
1
0.5%
|
| South Africa |
18
27.7%
|
16
24.6%
|
17
26.6%
|
51
26.3%
|
| Israel |
6
9.2%
|
6
9.2%
|
4
6.3%
|
16
8.2%
|
| Norway |
3
4.6%
|
3
4.6%
|
4
6.3%
|
10
5.2%
|
| Netherlands |
3
4.6%
|
3
4.6%
|
4
6.3%
|
10
5.2%
|
| Hungary |
6
9.2%
|
7
10.8%
|
6
9.4%
|
19
9.8%
|
| New Zealand |
2
3.1%
|
1
1.5%
|
2
3.1%
|
5
2.6%
|
| Slovakia |
2
3.1%
|
0
0%
|
2
3.1%
|
4
2.1%
|
| Czech Republic |
2
3.1%
|
5
7.7%
|
3
4.7%
|
10
5.2%
|
| Statin Status (participants) [Number] | ||||
| non-naive |
48
73.8%
|
50
76.9%
|
49
76.6%
|
147
75.8%
|
| naive |
17
26.2%
|
15
23.1%
|
15
23.4%
|
47
24.2%
|
| Tanner Stage (participants) [Number] | ||||
| I |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| II |
9
13.8%
|
15
23.1%
|
15
23.4%
|
39
20.1%
|
| III |
20
30.8%
|
16
24.6%
|
16
25%
|
52
26.8%
|
| IV |
23
35.4%
|
19
29.2%
|
20
31.3%
|
62
32%
|
| V |
13
20%
|
15
23.1%
|
13
20.3%
|
41
21.1%
|
| Body Mass Index (kg/m2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg/m2] |
21.9
(4.30)
|
23.4
(6.14)
|
22.2
(4.75)
|
22.5
(5.14)
|
| height (cm) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [cm] |
164.8
(10.35)
|
160.7
(10.90)
|
162.1
(11.94)
|
162.5
(11.16)
|
| weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
60.3
(15.32)
|
61.5
(20.77)
|
59.0
(16.81)
|
60.3
(17.72)
|
Outcome Measures
| Title | Percent Change in Plasma Low Density Lipoprotein-cholesterol (LDL-C) From Day 1 (Study Baseline) to Week 8. |
|---|---|
| Description | Percent change in LDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline)to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population. |
| Time Frame | 8 weeks (week 8 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam |
|---|---|---|---|
| Arm/Group Description | Placebo similar to active | Low dose colesevelam 1.9 grams per day | High dose colesevelam 3.8 grams per day |
| Measure Participants | 65 | 63 | 63 |
| Mean (Standard Deviation) [percent change from baseline] |
2.9
(16.46)
|
-3.7
(18.36)
|
-10.6
(19.36)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Low Dose Colesevelam |
|---|---|---|
| Comments | The primary null hypotheses were tested sequentially in the following order: 1) no difference between the high-dose colesevelam HCl and placebo for percent change in LDL-C from study baseline to Week 8 endpoint with the last observation carried forward (LOCF) and 2) no difference between the low-dose colesevelam HCl and placebo for percent change in LDL-C from study baseline to Week 8 endpoint with LOCF. The hypotheses were tested at a 2-sided significance level of 5%. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1122 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, High Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Percent Change in Plasma Total Cholesterol (TC) From Day 1 (Study Baseline) to Week 8. |
|---|---|
| Description | Percent change in total cholesterol (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population. |
| Time Frame | 8 weeks (week 8 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam |
|---|---|---|---|
| Arm/Group Description | Placebo similar to active | Low dose colesevelam 1.9 grams per day | High dose colesevelam 3.8 grams per day |
| Measure Participants | 65 | 63 | 63 |
| Mean (Standard Deviation) [percent change from baseline] |
2.9
(13.29)
|
-1.1
(14.22)
|
-5.4
(15.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Low Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5260 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, High Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0085 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Percent Change in Plasma Triglycerides (TG) From Day 1 (Study Baseline) to Week 8. |
|---|---|
| Description | Percent change in triglycerides (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population. |
| Time Frame | 8 weeks (week 8 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam |
|---|---|---|---|
| Arm/Group Description | Placebo similar to active | Low dose colesevelam 1.9 grams per day | High dose colesevelam 3.8 grams per day |
| Measure Participants | 65 | 63 | 63 |
| Mean (Standard Deviation) [percent change from baseline] |
12.5
(40.8)
|
16.9
(35.7)
|
12.5
(53.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Low Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, High Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Percent Change in Plasma High-density Lipoprotein-cholesterol (HDL-C) From Day 1 (Study Baseline) to Week 8. |
|---|---|
| Description | Percent change in HDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population. |
| Time Frame | 8 weeks (week 8 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam |
|---|---|---|---|
| Arm/Group Description | Placebo similar to active | Low dose colesevelam 1.9 grams per day | High dose colesevelam 3.8 grams per day |
| Measure Participants | 65 | 63 | 63 |
| Mean (Standard Deviation) [percent change from baseline] |
2.5
(12.52)
|
3.9
(12.45)
|
8.5
(14.72)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Low Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0155 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, High Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Percent Change in Plasma Non-high Density Lipoprotein-cholesterol (Non-HDL-C) From Day 1 (Study Baseline) to Week 8. |
|---|---|
| Description | Percent change in non-HDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population. |
| Time Frame | 8 weeks (week 8 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population for Double blind Period. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam |
|---|---|---|---|
| Arm/Group Description | Placebo similar to active | Low dose colesevelam 1.9 grams per day | High dose colesevelam 3.8 grams per day |
| Measure Participants | 65 | 63 | 63 |
| Mean (Standard Deviation) [percent change from baseline] |
3.4
(16.01)
|
-2.1
(17.32)
|
-8.4
(18.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Low Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3482 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, High Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0006 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Percent Change in Plasma Apolipoprotien A-I (Apo A-1) From Day 1 (Study Baseline) to Week 8. |
|---|---|
| Description | Percent change in Apolipoprotien A-I (Apo A-1) (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population. |
| Time Frame | 8 weeks (week 8 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population in Double blind Period. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam |
|---|---|---|---|
| Arm/Group Description | Placebo similar to active | Low dose colesevelam 1.9 grams per day | High dose colesevelam 3.8 grams per day |
| Measure Participants | 63 | 62 | 61 |
| Mean (Standard Deviation) [percent change from baseline] |
4.4
(14.62)
|
7.0
(13.96)
|
11.2
(16.79)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Low Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, High Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Percent Change in Plasma Apolipoprotein B (Apo B) From Day 1 (Study Baseline) to Week 8. |
|---|---|
| Description | Percent change in Apo B (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population. |
| Time Frame | 8 weeks (week 8 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population in Double blind Period. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam |
|---|---|---|---|
| Arm/Group Description | Placebo similar to active | Low dose colesevelam 1.9 grams per day | High dose colesevelam 3.8 grams per day |
| Measure Participants | 63 | 62 | 61 |
| Mean (Standard Deviation) [percent change from baseline] |
2.3
(14.78)
|
-0.7
(16.52)
|
-7.0
(14.45)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Low Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7433 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, High Dose Colesevelam |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Study Baseline (Day 1) to Week 26. |
|---|---|
| Description | Percent change in low-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period. |
| Time Frame | 26 weeks (week 26 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam | All High Dose Colesevelam in Open Label Extension |
|---|---|---|---|---|
| Arm/Group Description | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to placebo treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to low dose colesevelam 1.9 grams per day treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to high dose colesevelam 3.8 grams per day treatment during the Double blind Period. | Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose). |
| Measure Participants | 62 | 56 | 60 | 178 |
| Mean (Standard Deviation) [percent change from baseline] |
-11.9
(22.39)
|
-16.8
(19.85)
|
-13.5
(21.58)
|
-14.0
(21.32)
|
| Title | Percent Change in Total Cholesterol From Study Baseline (Day 1) to Week 26. |
|---|---|
| Description | Percent change in total cholesterol (TC) from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period. |
| Time Frame | 26 weeks (week 26 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam | All High Dose Colesevelam in Open Label Extension |
|---|---|---|---|---|
| Arm/Group Description | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to placebo treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to low dose colesevelam 1.9 grams per day treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to high dose colesevelam 3.8 grams per day treatment during the Double blind Period. | Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose). |
| Measure Participants | 62 | 56 | 60 | 178 |
| Mean (Standard Deviation) [percent change from baseline] |
-7.5
(17.21)
|
-9.1
(16.91)
|
-7.5
(17.55)
|
-8.0
(17.15)
|
| Title | Percent Change in Triglycerides From Study Baseline (Day 1) to Week 26. |
|---|---|
| Description | Percent change in triglycerides from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period. |
| Time Frame | 26 weeks (week 26 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam | All High Dose Colesevelam in Open Label Extension |
|---|---|---|---|---|
| Arm/Group Description | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to placebo treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to low dose colesevelam 1.9 grams per day treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to high dose colesevelam 3.8 grams per day treatment during the Double blind Period. | Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose). |
| Measure Participants | 62 | 56 | 60 | 178 |
| Mean (Standard Deviation) [percent change from baseline] |
-5.3
(59.1)
|
19.5
(58.0)
|
14.2
(64.5)
|
11.5
(61.8)
|
| Title | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Study Baseline (Day 1) to Week 26. |
|---|---|
| Description | Percent change in high-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period. |
| Time Frame | 26 weeks (week 26 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam | All High Dose Colesevelam in Open Label Extension |
|---|---|---|---|---|
| Arm/Group Description | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to placebo treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to low dose colesevelam 1.9 grams per day treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to high dose colesevelam 3.8 grams per day treatment during the Double blind Period. | Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose). |
| Measure Participants | 62 | 56 | 60 | 178 |
| Mean (Standard Deviation) [percent change from baseline] |
6.6
(13.64)
|
8.5
(20.33)
|
9.3
(19.37)
|
8.1
(17.86)
|
| Title | Percent Change in Non-high-density Lipoprotein Cholesterol From Study Baseline (Day 1) to Week 26. |
|---|---|
| Description | Percent change in non-high-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period. |
| Time Frame | 26 weeks (week 26 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam | All High Dose Colesevelam in Open Label Extension |
|---|---|---|---|---|
| Arm/Group Description | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to placebo treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to low dose colesevelam 1.9 grams per day treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to high dose colesevelam 3.8 grams per day treatment during the Double blind Period. | Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose). |
| Measure Participants | 61 | 56 | 60 | 177 |
| Mean (Standard Deviation) [percent change from baseline] |
-10.0
(21.04)
|
-13.2
(19.9)
|
-11.0
(20.80)
|
-11.3
(20.53)
|
| Title | Percent Change in Apolipoprotein A-I From Study Baseline (Day 1) to Week 26. |
|---|---|
| Description | Percent change in apolipoprotein A-I from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period. |
| Time Frame | 26 weeks (week 26 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam | All High Dose Colesevelam in Open Label Extension |
|---|---|---|---|---|
| Arm/Group Description | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to placebo treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to low dose colesevelam 1.9 grams per day treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to high dose colesevelam 3.8 grams per day treatment during the Double blind Period. | Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose). |
| Measure Participants | 52 | 52 | 57 | 161 |
| Mean (Standard Deviation) [percent change from baseline] |
4.7
(12.95)
|
4.9
(14.86)
|
7.2
(15.34)
|
5.6
(14.40)
|
| Title | Percent Change in Apolipoprotein B From Study Baseline (Day 1) to Week 26. |
|---|---|
| Description | Percent change in apolipoprotein B from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period. |
| Time Frame | 26 weeks (week 26 - day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population. Last Observation Carried Forward. |
| Arm/Group Title | Placebo | Low Dose Colesevelam | High Dose Colesevelam | All High Dose Colesevelam in Open Label Extension |
|---|---|---|---|---|
| Arm/Group Description | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to placebo treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to low dose colesevelam 1.9 grams per day treatment during the Double blind Period. | A subpopulation of the All High Dose treatment regimen of the Open Label Extension period of participants who were randomized to high dose colesevelam 3.8 grams per day treatment during the Double blind Period. | Open Label Extension was an 18 week open-label treatment period. All participants were treated with 3750 mg colesevelam (high-dose). |
| Measure Participants | 52 | 52 | 57 | 161 |
| Mean (Standard Deviation) [percent change from baseline] |
-11.4
(16.86)
|
-11.3
(18.71)
|
-11.2
(17.86)
|
-11.3
(17.72)
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Placebo Double Blind Period | Low Dose Colesevelam Double Blind Period | High Dose Colesevelam Double Blind Period | High Dose Colesevelam Open Label Extension | ||||
| Arm/Group Description | Placebo taken from day 1 to week 8. | Low dose colesevelam 1.9 grams per day taken from day 1 to week 8. | High dose colesevelam 3.8 grams per day taken from day 1 to week 8. | All participants of the Open Label Extension (weeks 8-26) took colesevelam 3.8 grams per day. | ||||
All Cause Mortality |
||||||||
| Placebo Double Blind Period | Low Dose Colesevelam Double Blind Period | High Dose Colesevelam Double Blind Period | High Dose Colesevelam Open Label Extension | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Placebo Double Blind Period | Low Dose Colesevelam Double Blind Period | High Dose Colesevelam Double Blind Period | High Dose Colesevelam Open Label Extension | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/65 (4.6%) | 3/65 (4.6%) | 0/64 (0%) | 0/184 (0%) | ||||
| Blood and lymphatic system disorders | ||||||||
| idiopathic thrombocytopenic purpura | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 | 0/64 (0%) | 0 | 0/184 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||||
| renal hypoplasia | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 | 0/64 (0%) | 0 | 0/184 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| gastroesophageal reflux disease | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 | 0/64 (0%) | 0 | 0/184 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| poisoning deliberate | 1/65 (1.5%) | 1 | 0/65 (0%) | 0 | 0/64 (0%) | 0 | 0/184 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| nasopharyngeal cancer NOS | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 | 0/64 (0%) | 0 | 0/184 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| contusion | 0/65 (0%) | 0 | 1/65 (1.5%) | 1 | 0/64 (0%) | 0 | 0/184 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo Double Blind Period | Low Dose Colesevelam Double Blind Period | High Dose Colesevelam Double Blind Period | High Dose Colesevelam Open Label Extension | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/65 (30.8%) | 25/65 (38.5%) | 14/64 (21.9%) | 71/184 (38.6%) | ||||
| Gastrointestinal disorders | ||||||||
| vomiting NOS | 1/65 (1.5%) | 2/65 (3.1%) | 1/64 (1.6%) | 0/184 (0%) | ||||
| diarrhea NOS | 2/65 (3.1%) | 0/65 (0%) | 1/64 (1.6%) | 2/184 (1.1%) | ||||
| nausea | 1/65 (1.5%) | 2/65 (3.1%) | 0/64 (0%) | 7/184 (3.8%) | ||||
| abdominal pain NOS | 0/65 (0%) | 0/65 (0%) | 0/64 (0%) | 6/184 (3.3%) | ||||
| General disorders | ||||||||
| fatigue | 1/65 (1.5%) | 3/65 (4.6%) | 2/64 (3.1%) | 0/184 (0%) | ||||
| Infections and infestations | ||||||||
| nasopharyngitis | 3/65 (4.6%) | 4/65 (6.2%) | 4/64 (6.3%) | 10/184 (5.4%) | ||||
| upper respiratory infections NOS | 3/65 (4.6%) | 1/65 (1.5%) | 1/64 (1.6%) | 9/184 (4.9%) | ||||
| ear infection NOS | 3/65 (4.6%) | 1/65 (1.5%) | 0/64 (0%) | 3/184 (1.6%) | ||||
| gastrointestinal viral NOS | 2/65 (3.1%) | 0/65 (0%) | 0/64 (0%) | 4/184 (2.2%) | ||||
| influenza | 0/65 (0%) | 0/65 (0%) | 2/64 (3.1%) | 7/184 (3.8%) | ||||
| Investigations | ||||||||
| blood creatine phosphokinase increased | 0/65 (0%) | 2/65 (3.1%) | 1/64 (1.6%) | 0/184 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| myalgia | 0/65 (0%) | 2/65 (3.1%) | 0/64 (0%) | 0/184 (0%) | ||||
| Nervous system disorders | ||||||||
| headache | 2/65 (3.1%) | 3/65 (4.6%) | 2/64 (3.1%) | 14/184 (7.6%) | ||||
| dizziness | 2/65 (3.1%) | 0/65 (0%) | 0/64 (0%) | 0/184 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| rhinitis NOS | 0/65 (0%) | 3/65 (4.6%) | 0/64 (0%) | 3/184 (1.6%) | ||||
| pharyngolaryngeal pain | 0/65 (0%) | 2/65 (3.1%) | 0/64 (0%) | 6/184 (3.3%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor reflects the following restrictive language in the Clinical Study Agreements: "If identified by Daiichi Sankyo,Inc. (DSI), any of DSI's confidential information as defined herein shall be deleted…Nothing in this publication section shall be taken as giving DSI any right of editorial control over any publication prepared by the Study Site."
Results Point of Contact
| Name/Title | Howard Kessler |
|---|---|
| Organization | Daiichi Sankyo |
| Phone | 732-590-5032 |
| hmkessler@dsi.com |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00145574
Other Study ID Numbers:
- WEL-410
First Posted:
Sep 5, 2005
Last Update Posted:
Apr 15, 2010
Last Verified:
Apr 1, 2010