Efficacy of Alogliptin and With Pioglitazone in Patients With Type 2 Diabetes.
Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT00655863
Collaborator
(none)
71
2
3
29
35.5
1.2
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the efficacy of Alogliptin, once daily (QD), taken by itself and with pioglitazone on postprandial lipid measures in type 2 diabetes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
SYR-322 (alogliptin) is a selective, orally available inhibitor of dipeptidyl peptidase IV being developed as a treatment for type 2 diabetes mellitus. Dipeptidyl peptidase IV is the primary enzyme involved in the in vivo degradation of at least 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide.
Pioglitazone HCl (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan). Pioglitazone HCl depends on the presence of insulin for its mechanism of action.
This study will assess the effects of alogliptin and alogliptin coadministered with pioglitazone HCl on postprandial lipid and lipoprotein metabolism in participants with type 2 diabetes. Individuals who participate in this study will be required to commit to a screening visit and up to 6 additional visits at the study center. Study participation is anticipated to be about 20 weeks (or approximately 5 months). Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations and electrocardiograms. At 3 of the visits a meal will be served that must be eaten within 10 minutes.
Study Design
Study Type:
Interventional
Actual Enrollment
:
71 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing SYR-322 Alone and Combination SYR-322 With Pioglitazone Versus Placebo on Postprandial Lipids in Subjects With Type 2 Diabetes
Study Start Date
:
Jul 1, 2007
Actual Primary Completion Date
:
Dec 1, 2009
Actual Study Completion Date
:
Dec 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo QD
|
Drug: Placebo
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.
Other Names:
|
| Experimental: Alogliptin 25 mg QD
|
Drug: Alogliptin
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.
Other Names:
|
| Experimental: Alogliptin 25 mg QD + Pioglitazone 30 mg QD
|
Drug: Alogliptin and Pioglitazone
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 16. [Baseline and Week 16.]
The change in postprandial (after eating a meal) incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC (0-8h)) postdose at week 16 relative to baseline.
Secondary Outcome Measures
- Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 4. [Baseline and Week 4.]
The change in postprandial incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC(0-8h)) postdose at week 4 relative to baseline.
- Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. [Baseline, Week 4 and Week 16.]
The change in postprandial incremental area under the plasma concentration-time curve for very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL2 cholesterol, VLDL2 triglycerides, chylomicron cholesterol, chylomicron triglycerides, intermediate-density lipoprotein (IDL) cholesterol, and IDL triglycerides from 0 to 8 hours postdose at week 4 and week 16 relative to baseline.
- Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. [Baseline, Week 4 and Week 16.]
Postprandial incremental area under the curve changes for very-low-density lipoprotein (VLDL) Apo B-48, VLDL Apo B 100, VLDL2 Apo B-48, VLDL2 Apo B 100, chylomicron Apo B-48, chylomicron Apo B 100, and intermediate density lipoprotein (IDL) Apo B-48, IDL Apo B 100, and triglyceride-rich remnant (TRR) lipoproteins from 0 to 8 hours postdose at week 4 and week 16 relative to baseline.
- Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) [Baseline, Week 4 and Week 16.]
Postprandial changes over time at each week indicated relative to baseline.
- Postprandial Changes Over Time From Baseline for Glucose [Baseline, Week 4 and Week 16.]
Postprandial changes over time at each week indicated relative to baseline.
- Postprandial Changes Over Time From Baseline for Insulin [Baseline, Week 4 and Week 16.]
Postprandial changes over time at each week indicated relative to baseline.
- Postprandial Changes Over Time From Baseline for Glucagon [Baseline, Week 4 and Week 16.]
Postprandial changes over time at each week indicated relative to baseline.
- Change From Baseline in Glycosylated Hemoglobin [Baseline, Week 8 and Week 16.]
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated relative to baseline.
- Change From Baseline in Fasting Plasma Glucose [Baseline, Week 4, Week 8 and Week 16.]
The change in fasting plasma glucose collected at each week indicated relative to baseline.
- Change From Baseline in Postprandial C-Peptide [Baseline, Week 4 and Week 16.]
The change in postprandial C-peptide collected at each week indicated relative to baseline.
- Change From Baseline in Postprandial Proinsulin [Baseline, Week 4 and Week 16.]
The change in postprandial proinsulin collected at each week indicated relative to baseline.
- Change From Baseline in High-sensitive C-reactive Protein (Hs-CRP) [Baseline, Week 4 and Week 16.]
The change in hs-CRP collected at each week indicated relative to baseline.
- Change From Baseline in Adiponectin [Baseline, Week 4 and Week 16.]
The change in adiponectin collected at each week indicated relative to baseline.
- Change From Baseline in Anti-Vascular Cell Adhesion Molecule (VCAM) [Baseline, Week 4 and Week 16.]
The change in VCAM collected at each week indicated relative to baseline.
- Change From Baseline in Anti-Intercellular Adhesion Molecule (ICAM) [Baseline, Week 4 and Week 16.]
The change in ICAM collected at each week indicated relative to baseline.
- Change From Baseline in e-Selectin [Baseline, Week 4 and Week 16.]
The change in e-Selectin collected at each week indicated relative to baseline.
- Change From Baseline in Endothelial Function Through Pulse Wave Tonometry [Baseline and Week 16.]
Pulse wave tonometry performed before the meal and 2 hours postmeal using one recording consisting of 15 to 20 sequentially recorded radial artery waveforms collected at each assessment.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria
-
Diagnosis of type 2 diabetes
-
Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
-
Either failed treatment with diet and exercise for 3 months prior to Screening or has been receiving a stable dose of metformin, sulfonylurea, nateglinide, or repaglinide for more than 3 months prior to Screening.
-
Inadequate glycemic control as defined by glycosylated hemoglobin concentration between 6.5 and 9.0%, inclusive.
-
Fasting plasma glucose less than 13.3 mmol per L.
-
Fasting serum triglyceride level of 1.7 to 5.0 mmol per L, inclusive.
-
Has not been receiving any lipid-lowering therapy within 3 months prior to Screening or on a stable statin and/or ezetimibe therapy (same drug and dose) for at least 3 months.
-
Body mass index greater than 23 kg/m2 and less than 45 kg/m2.
-
If has regular use of other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening. Use of as needed prescription medications and over-the-counter medications is allowed at the discretion of the investigator.
-
Is to be Apolipoprotein E 3/3 or Apolipoprotein E 3/4 phenotype positive prior to baseline.
Exclusion Criteria
-
History of type 1 diabetes.
-
History of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years.
-
Diastolic blood pressure greater than 100 mm Hg or a systolic blood pressure of greater than 160 mm Hg.
-
History of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study medication.
-
Hemoglobin less than 120 g per L for males and less than100 g per L for females.
-
Alanine transaminase level greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
-
Serum creatinine level greater than 133 μmol per L.
-
Fasting total cholesterol greater than 6.5 mmol per L.
-
New York Heart Association heart failure of any Class (I-IV) regardless of therapy.
-
History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.
-
History of acute metabolic diabetic complications.
-
History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.
-
History of infection with human immunodeficiency virus.
-
History of diabetic gastro paresis.
-
History of gastric bypass surgery.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Amsterdam | Netherlands | |||
| 2 | Gothenburg | Sweden |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Medical Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT00655863
Other Study ID Numbers:
- SYR-322_301
- 2007-000486-38
- U1111-1113-2081
- NL22649.029.08
First Posted:
Apr 10, 2008
Last Update Posted:
May 27, 2013
Last Verified:
May 1, 2013
Keywords provided by Takeda
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants enrolled at 2 investigative sites in The Netherlands and Sweden from 16 July 2007 to 17 December 2009. |
|---|---|
| Pre-assignment Detail | Participants with a historical diagnosis of type 2 diabetes mellitus were enrolled in one of three, once-daily (QD) treatment groups. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Period Title: Overall Study | |||
| STARTED | 24 | 25 | 22 |
| COMPLETED | 24 | 25 | 21 |
| NOT COMPLETED | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD | Total |
|---|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. | Total of all reporting groups |
| Overall Participants | 24 | 25 | 22 | 71 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
59.1
(6.23)
|
58.7
(6.47)
|
59.1
(6.94)
|
59.0
(6.45)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
4
16.7%
|
10
40%
|
7
31.8%
|
21
29.6%
|
| Male |
20
83.3%
|
15
60%
|
15
68.2%
|
50
70.4%
|
| Region of Enrollment (participants) [Number] | ||||
| Netherlands |
9
37.5%
|
10
40%
|
9
40.9%
|
28
39.4%
|
| Sweden |
15
62.5%
|
15
60%
|
13
59.1%
|
43
60.6%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| Count of Participants [Participants] |
24
100%
|
25
100%
|
22
100%
|
71
100%
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
101.83
(11.989)
|
93.68
(10.816)
|
93.05
(13.160)
|
96.24
(12.471)
|
| Height (cm) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [cm] |
178.3
(6.74)
|
173.9
(8.17)
|
172.8
(10.97)
|
175.0
(8.91)
|
| Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg/m2] |
32.12
(3.997)
|
31.09
(4.196)
|
31.15
(3.503)
|
31.46
(3.898)
|
| Diabetes duration (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
5.55
(3.243)
|
6.40
(3.622)
|
5.03
(3.791)
|
5.69
(3.548)
|
Outcome Measures
| Title | Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 16. |
|---|---|
| Description | The change in postprandial (after eating a meal) incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC (0-8h)) postdose at week 16 relative to baseline. |
| Time Frame | Baseline and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 21 |
| Least Squares Mean (Standard Error) [mg.h/dL] |
-39.728
(48.2481)
|
-346.957
(47.2251)
|
-293.439
(51.1271)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo QD, Alogliptin 25 mg QD |
|---|---|---|
| Comments | The null hypothesis that there was no difference between Alogliptin 25 mg QD and placebo groups was tested at a 2-sided 0.05 significance level. The ANCOVA model used for the change in postprandial incremental area the curver for total triglycerides includes treatment and statin use as fixed effects and baseline AUC(0-8h) for total triglycerides as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value and confidence interval presented without multiplicity adjustment. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -307.229 | |
| Confidence Interval |
(2-Sided) 95% -443.168 to -171.290 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo QD, Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|
| Comments | The null hypothesis that there was no difference between Alogliptin 25 mg QD + Pioglitazone 30 mg QD and placebo QD groups was tested at a 2-sided 0.05 significance level. The ANCOVA model used for the change in postprandial incremental area the curve for total triglycerides includes treatment and statin use as fixed effects and baseline AUC(0-8h) for total triglycerides as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value and confidence interval presented without multiplicity adjustment. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -253.711 | |
| Confidence Interval |
() 95% -394.161 to -113.262 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 4. |
|---|---|
| Description | The change in postprandial incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC(0-8h)) postdose at week 4 relative to baseline. |
| Time Frame | Baseline and Week 4. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 21 | 19 |
| Least Squares Mean (Standard Error) [mg.h/dL] |
-16.291
(61.1286)
|
-288.490
(65.4530)
|
-279.116
(68.4947)
|
| Title | Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. |
|---|---|
| Description | The change in postprandial incremental area under the plasma concentration-time curve for very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL2 cholesterol, VLDL2 triglycerides, chylomicron cholesterol, chylomicron triglycerides, intermediate-density lipoprotein (IDL) cholesterol, and IDL triglycerides from 0 to 8 hours postdose at week 4 and week 16 relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| VLDL triglycerides Week 4 (n=23; n=21; n=19) |
-9.488
(35.4108)
|
-119.009
(37.0255)
|
-98.758
(38.9818)
|
| VLDL triglycerides Week 16 (n=23; n=25; n=21) |
25.194
(29.4896)
|
-130.459
(28.2397)
|
-85.709
(30.7867)
|
| VLDL cholesterol Week 4 (n=23; n=21; n=19) |
-6.914
(4.3110)
|
-14.760
(4.4843)
|
-10.760
(4.7065)
|
| VLDL cholesterol Week 16 (n=23; n=25; n=21) |
-4.561
(3.4790)
|
-16.365
(3.3125)
|
-8.747
(3.5984)
|
| VLDL 2 triglycerides Week 4 (n=23; n=20; n=19) |
-5.221
(7.8102)
|
-17.960
(8.3710)
|
-8.687
(8.6678)
|
| VLDL 2 triglycerides Week 16 (n=23; n=25; n=21) |
-24.280
(3.4497)
|
-18.986
(3.3104)
|
-23.061
(3.6369)
|
| VLDL 2 cholesterol Week 4 (n=23; n=20; n=19) |
-2.396
(0.8474)
|
-0.709
(0.9059)
|
-1.073
(0.9345)
|
| VLDL 2 cholesterol Week 16 (n=23; n=25; n=21) |
-2.190
(0.7833)
|
-1.445
(0.7506)
|
-1.232
(0.8217)
|
| Chylomicron triglycerides Week 4 (n=23; n=21; n=1 |
0.617
(26.1603)
|
-115.093
(27.4280)
|
-108.036
(28.6857)
|
| Chylomicron triglycerides Week 16(n=23;n=25; n=21) |
-18.577
(15.2943)
|
-136.626
(14.6683)
|
-129.991
(15.9053)
|
| Chylomicron cholesterol Week 4 (n=23; n=21; n=19) |
-0.091
(1.1845)
|
-4.474
(1.2425)
|
-3.628
(1.3039)
|
| Chylomicron cholesterol Week 16 (n=23; n=25; n=21) |
-1.431
(0.6001)
|
-5.566
(0.5769)
|
-4.289
(0.6265)
|
| IDL triglycerides Week 4 (n=22; n=18; n=17) |
14.667
(12.9991)
|
-6.771
(14.3964)
|
-4.410
(14.9182)
|
| IDL triglycerides Week 16 (n=22; n=23; n=19) |
-0.313
(2.9265)
|
-4.045
(2.8759)
|
-4.533
(3.1885)
|
| IDL cholesterol Week 4 (n=22; n=18; n=17) |
1.473
(1.5215)
|
-0.808
(1.6835)
|
0.195
(1.7328)
|
| IDL cholesterol Week 16 (n=22; n=23; n=19) |
0.171
(0.6006)
|
0.249
(0.5893)
|
0.609
(0.6499)
|
| Title | Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. |
|---|---|
| Description | Postprandial incremental area under the curve changes for very-low-density lipoprotein (VLDL) Apo B-48, VLDL Apo B 100, VLDL2 Apo B-48, VLDL2 Apo B 100, chylomicron Apo B-48, chylomicron Apo B 100, and intermediate density lipoprotein (IDL) Apo B-48, IDL Apo B 100, and triglyceride-rich remnant (TRR) lipoproteins from 0 to 8 hours postdose at week 4 and week 16 relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| VLDL apo B-48 Week 4 (n=19; n=12; n=15) |
-0.020
(0.2902)
|
-0.491
(0.3572)
|
-0.312
(0.3180)
|
| VLDL apo B-48 Week 16 (n=19; n=16; n=16) |
-0.055
(0.1956)
|
-0.654
(0.2077)
|
-0.266
(0.2044)
|
| VLDL apo B 100 Week 4 (n=19; n=12; n=15) |
0.568
(2.2981)
|
-2.670
(2.8906)
|
-2.977
(2.5811)
|
| VLDL apo B 100 Week 16 (n=19; n=16; n=16) |
-0.453
(1.8388)
|
-6.967
(2.0109)
|
-3.265
(2.0025)
|
| VLDL2 apo B-48 Week 4 (n=19; n=12; n=15) |
-0.075
(0.0776)
|
-0.101
(0.0969)
|
-0.022
(0.0870)
|
| VLDL2 apo B-48 Week 16 (n=19; n=16; n=16) |
-0.079
(0.0674)
|
-0.175
(0.0732)
|
0.002
(0.0737)
|
| VLDL2 apo B 100 Week 4 (n=19; n=12; n=15) |
0.464
(1.1846)
|
0.507
(1.4982)
|
-0.781
(1.33287)
|
| VLDL2 apo B 100 Week 16 (n=19; n=16; n=16) |
-1.155
(0.7985)
|
-2.049
(0.8732)
|
-1.793
(0.8707)
|
| Chylomicron apo B-48 Week 4 (n=19; n=12; n=14) |
-0.051
(0.0236)
|
-0.097
(0.0302)
|
-0.071
(0.0272)
|
| Chylomicron apo B-48 Week 16 (n=19; n=16; n=16) |
-0.051
(0.0180)
|
-0.113
(0.0197)
|
-0.084
(0.0191)
|
| Chylomicron apo B 100 Week 4(n=19; n=12; n=14) |
-0.123
(0.0825)
|
-0.417
(0.1041)
|
-0.389
(0.0960)
|
| Chylomicron apo B 100 Week 16 (n=19; n=16; n=16) |
-0.120
(0.0544)
|
-0.419
(0.0594)
|
-0.409
(0.0590)
|
| IDL apo B-48 Week 4 (n=18; n=10; n=13) |
0.002
(0.1254)
|
-0.247
(0.1707)
|
-0.223
(0.1476)
|
| IDL apo B-48 Week 16 (n=18; n=14; n=14) |
0.151
(0.1368)
|
-0.188
(0.1580)
|
0.021
(0.1561)
|
| IDL apo B 100 Week 4 (n=18; n=10; n=13) |
0.952
(3.3778)
|
-2.029
(4.5494)
|
-2.769
(3.8565)
|
| IDL apo B 100 Week 16 (n=18; n=14; n=14) |
4.181
(3.4923)
|
-2.876
(3.9944)
|
0.073
(3.8906)
|
| TRR lipoproteins Week 4 (n=24; n=21; n=19) |
16.147
(5.6739)
|
-1.071
(6.0930)
|
-5.673
(6.4428)
|
| TRR lipoproteins Week 16 (n=24; n=25; n=21) |
2.818
(3.1250)
|
-12.719
(3.0884)
|
-7.853
(3.3658)
|
| Title | Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) |
|---|---|
| Description | Postprandial changes over time at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 4: 1 hour postprandial (n=20; n=17; n=15) |
0.52
(1.167)
|
-5.48
(1.249)
|
-4.88
(1.330)
|
| Week 4: 2 hours postprandial (n=21; n=17; n=16) |
0.92
(1.524)
|
-2.93
(1.702)
|
-6.41
(1.732)
|
| Week 4: 3 hours postprandial (n=21; n=17; n=16) |
1.20
(1.619)
|
-2.08
(1.789)
|
-3.61
(1.848)
|
| Week 4: 4 hours postprandial (n=21; n=17; n=16) |
1.76
(1.823)
|
2.86
(2.027)
|
-0.84
(2.077)
|
| Week 4: 8 hours postprandial (n=19; n=16; n=16) |
-1.01
(0.955)
|
-0.38
(1.039)
|
-0.72
(1.040)
|
| Week 16: 1 hour postprandial (n=21 ; n=20; n=16) |
-0.28
(1.304)
|
-4.10
(1.326)
|
-3.63
(1.462)
|
| Week 16: 2 hours postprandial (n=21; n=21; n=17) |
-3.59
(1.451)
|
-3.75
(1.457)
|
-3.75
(1.599)
|
| Week 16: 3 hours postprandial (n=21; n=21; n=17) |
-1.08
(1.206)
|
-2.25
(1.202)
|
-3.17
(1.326)
|
| Week 16: 4 hours postprandial (n=21; n=21; n=17) |
-0.64
(1.263)
|
-1.88
(1.271)
|
-1.83
(1.393)
|
| Week 16: 8 hours postprandial (n=21; n=21; n=17) |
-1.36
(0.820)
|
0.03
(0.819)
|
-1.48
(0.910)
|
| Title | Postprandial Changes Over Time From Baseline for Glucose |
|---|---|
| Description | Postprandial changes over time at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 4: 1 hour postprandial (n=24; n=21; n=19) |
-5.957
(5.3970)
|
-35.065
(5.7617)
|
-65.905
(6.0315)
|
| Week 4: 2 hours postprandial (n=23; n=21; n=19) |
-4.049
(5.9932)
|
-24.721
(6.2299)
|
-67.718
(6.5647)
|
| Week 4: 3 hours postprandial (n=24; n=21; n=18) |
3.200
(6.3047)
|
-19.367
(6.7356)
|
-54.345
(7.2106)
|
| Week 4: 4 hours postprandial (n=24; n=21; n=19) |
2.930
(5.3775)
|
-13.907
(5.6699)
|
-48.643
(6.0151)
|
| Week 4: 8 hours postprandial (n=22; n=21; n=19) |
0.046
(4.1120)
|
-6.077
(4.2043)
|
-27.856
(4.3961)
|
| Week 16: 1 hour postprandial (n=24; n=25; n=21) |
11.867
(8.1356)
|
-36.189
(7.9793)
|
-58.168
(8.6585)
|
| Week 16: 2 hours postprandial (n=23; n=25; n=21) |
17.324
(8.6572)
|
-29.745
(8.2830)
|
-61.899
(9.0248)
|
| Week 16: 3 hours postprandial (n=24; n=25; n=20) |
18.379
(7.8017)
|
-16.996
(7.6465)
|
-51.891
(8.4838)
|
| Week 16: 4 hours postprandial (n=24; n=25; n=21) |
10.849
(7.3084)
|
-12.517
(7.1054)
|
-41.943
(7.7396)
|
| Week 16: 8 hours postprandial (n=24; n=25; n=21) |
3.266
(5.0112)
|
-5.737
(4.9335)
|
-19.381
(5.3350)
|
| Title | Postprandial Changes Over Time From Baseline for Insulin |
|---|---|
| Description | Postprandial changes over time at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 4: 1 hour postprandial (n=24; n=21; n=18) |
-5.047
(3.5562)
|
-5.867
(3.7749)
|
-18.287
(4.0906)
|
| Week 4: 2 hours postprandial (n=24; n=21; n=19) |
1.405
(6.3051)
|
3.161
(6.7294)
|
-28.700
(7.0572)
|
| Week 4: 3 hours postprandial (n=24; n=21; n=19) |
0.637
(5.2789)
|
0.652
(5.6125)
|
-18.842
(5.9301)
|
| Week 4: 4 hours postprandial (n=24; n=21; n=19) |
2.999
(3.5652)
|
5.092
(3.8075)
|
-12.891
(4.0088)
|
| Week 4: 8 hours postprandial (n=23; n=21; n=19) |
-1.174
(1.0270)
|
2.685
(1.0772)
|
-6.000
(1.1301)
|
| Week 16: 1 hour postprandial (n=24; n=25; n=21) |
-8.896
(4.8993)
|
-14.368
(4.7784)
|
-12.162
(5.2052)
|
| Week 16: 2 hours postprandial (n=24; n=25; n=21) |
-9.258
(6.5119)
|
-9.528
(6.4000)
|
-24.777
(6.9371)
|
| Week 16: 3 hours postprandial (n=24; n=25; n=21) |
4.447
(4.8889)
|
-9.848
(4.7800)
|
-23.025
(5.2049)
|
| Week 16: 4 hours postprandial (n=24; n=25; n=21) |
8.405
(4.5090)
|
-4.753
(4.4158)
|
-19.329
(4.8159)
|
| Week 16: 8 hours postprandial (n=24; n=25; n=21) |
0.495
(1.2847)
|
3.163
(1.2637)
|
-6.107
(1.3728)
|
| Title | Postprandial Changes Over Time From Baseline for Glucagon |
|---|---|
| Description | Postprandial changes over time at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 4: 1 hour postprandial (n=24; n=21; n=19) |
7.222
(3.7636)
|
-14.639
(4.0619)
|
-17.704
(4.2418)
|
| Week 4: 2 hours postprandial (n=24; n=21; n=19) |
1.730
(3.3262)
|
-17.015
(3.5627)
|
-22.081
(3.7541)
|
| Week 4: 3 hours postprandial (n=24; n=21; n=19) |
6.637
(3.7141)
|
-13.200
(3.9753)
|
-15.987
(4.2015)
|
| Week 4: 4 hours postprandial (n=24; n=20; n=18) |
2.021
(4.1496)
|
-4.679
(4.5627)
|
-8.860
(4.7910)
|
| Week 4: 8 hours postprandial (n=22; n=20; n=19) |
1.081
(3.5000)
|
-3.789
(3.6665)
|
-5.150
(3.7592)
|
| Week 16: 1 hour postprandial (n=24; n=25; n=21) |
3.318
(3.1819)
|
-16.955
(3.1477)
|
-17.462
(3.4144)
|
| Week 16: 2 hours postprandial (n=24; n=25; n=21) |
-1.047
(3.4159)
|
-20.949
(3.3556)
|
-20.662
(3.6653)
|
| Week 16: 3 hours postprandial (n=24; n=25; n=21) |
4.842
(3.4670)
|
-13.602
(3.4048)
|
10.84
(3.7260)
|
| Week 16: 4 hours postprandial (n=24; n=24; n=21) |
2.801
(3.1830)
|
-8.577
(3.1873)
|
-10.326
(3.4011)
|
| Week 16: 8 hours postprandial (n=24; n=25; n=21) |
3.917
(2.5383)
|
-5.818
(2.4876)
|
-9.332
(2.7108)
|
| Title | Change From Baseline in Glycosylated Hemoglobin |
|---|---|
| Description | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 8 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 21 |
| Week 8: fasting (n=23; n=24; n=20) |
-0.12
(0.084)
|
-0.55
(0.083)
|
-1.01
(0.090)
|
| Week 16: 5 minutes prior to meal (n=24;n=25; n=21) |
0.38
(0.131)
|
-0.39
(0.129)
|
-0.95
(0.140)
|
| Title | Change From Baseline in Fasting Plasma Glucose |
|---|---|
| Description | The change in fasting plasma glucose collected at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4, Week 8 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 4 (n=24; n=20; n=19) |
-4.141
(3.0027)
|
-20.669
(3.3024)
|
-38.826
(3.3890)
|
| Week 8 (n=24; n=25; n=21) |
4.864
(5.3254)
|
-16.293
(5.2451)
|
-38.242
(5.7203)
|
| Week 16 (n=24; n=25; n=21) |
11.869
(6.4897)
|
-17.052
(6.3918)
|
-38.481
(6.9709)
|
| Title | Change From Baseline in Postprandial C-Peptide |
|---|---|
| Description | The change in postprandial C-peptide collected at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 4: 1 hour postprandial (n=24; n=21; n=19) |
-0.106
(0.2597)
|
-0.300
(0.2775)
|
-1.199
(0.2921)
|
| Week 4: 2 hours postprandial (n=24; n=21; n=19) |
0.311
(0.3789)
|
-0.011
(0.4052)
|
-1.379
(0.4262)
|
| Week 4: 3 hours postprandial (n=24; n=21; n=19) |
0.376
(0.4386)
|
0.116
(0.4684)
|
-1.230
(0.4933)
|
| Week 4: 4 hours postprandial (n=24; n=21; n=19) |
0.256
(0.3674)
|
0.393
(0.3926)
|
-1.173
(0.4140)
|
| Week 4: 8 hours postprandial (n=23; n=20; n=19) |
-0.063
(0.1530)
|
0.421
(0.1643)
|
-0.911
(0.1699)
|
| Week 16: 1 hour postprandial (n=24; n=25; n=21) |
-0.176
(0.3474)
|
-1.021
(0.3405)
|
-0.646
(0.3712)
|
| Week 16: 2 hours postprandial (n=24; n=25; n=21) |
-0.011
(0.4337)
|
-1.006
(0.4259)
|
-1.055
(0.4638)
|
| Week 16: 3 hours postprandial (n=24; n=25; n=21) |
0.492
(0.4570)
|
-0.712
(0.4478)
|
-1.269
(0.4882)
|
| Week 16: 4 hours postprandial (n=24; n=25; n=21) |
0.496
(0.4042)
|
-0.068
(0.3961)
|
-1.515
(0.4323)
|
| Week 16: 8 hours postprandial (n=24; n=24; n=21) |
0.151
(0.2042)
|
0.588
(0.2047)
|
-0.761
(0.2194)
|
| Title | Change From Baseline in Postprandial Proinsulin |
|---|---|
| Description | The change in postprandial proinsulin collected at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 4: 1 hour postprandial (n=24; n=21; n=19) |
-4.555
(3.9248)
|
-13.024
(4.2068)
|
-41.192
(4.4562)
|
| Week 4: 2 hours postprandial (n=24; n=21; n=19) |
-0.208
(5.5216)
|
-12.568
(5.9505)
|
-56.478
(6.3185)
|
| Week 4: 3 hours postprandial (n=24; n=21; n=19) |
-6.735
(5.9547)
|
-12.987
(6.4485)
|
-59.573
(6.8034)
|
| Week 4: 4 hours postprandial (n=24; n=21; n=19) |
-6.496
(5.9756)
|
-6.848
(6.4875)
|
-52.649
(6.8526)
|
| Week 4: 8 hours postprandial (n=23; n=21; n=19) |
-5.082
(4.3735)
|
-5.561
(4.6395)
|
-35.159
(4.9287)
|
| Week 16: 1 hour postprandial (n=24; n=25; n=21) |
2.081
(5.3253)
|
-22.812
(5.2274)
|
-30.658
(5.7287)
|
| Week 16: 2 hours postprandial (n=24; n=25; n=21) |
3.336
(6.3373)
|
-29.930
(6.2396)
|
-45.487
(6.8516)
|
| Week 16: 3 hours postprandial (n=24; n=25; n=21) |
5.863
(6.2769)
|
-27.768
(6.2041)
|
-50.058
(6.7783)
|
| Week 16: 4 hours postprandial (n=24; n=25; n=21) |
8.671
(5.7153)
|
-21.862
(5.6549)
|
-48.757
(6.1834)
|
| Week 16: 8 hours postprandial (n=24; n=25; n=21) |
6.935
(5.2859)
|
-6.898
(5.2307)
|
-28.776
(5.7372)
|
| Title | Change From Baseline in High-sensitive C-reactive Protein (Hs-CRP) |
|---|---|
| Description | The change in hs-CRP collected at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 4: 5 minutes prior to meal (n=24; n=21; n=19) |
-1.514
(1.0846)
|
0.631
(1.1693)
|
0.155
(1.2269)
|
| Week 16: 5 minutes prior to meal (n=24; n=25;n=21) |
4.338
(2.6070)
|
-0.402
(2.5683)
|
-0.402
(2.8000)
|
| Title | Change From Baseline in Adiponectin |
|---|---|
| Description | The change in adiponectin collected at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 21 |
| Week 4: 5 minutes prior to meal (n=24;n=21; n=19) |
0.001
(0.0004)
|
0.000
(0.0005)
|
0.006
(0.0005)
|
| Week 16: 5 minutes prior to meal (n=24;n=25;n=21) |
0.000
(0.0005)
|
0.000
(0.0005)
|
0.007
(0.0005)
|
| Title | Change From Baseline in Anti-Vascular Cell Adhesion Molecule (VCAM) |
|---|---|
| Description | The change in VCAM collected at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 21 |
| Week 4: 5 minutes prior to meal (n=24;n=21; n=19) |
-37.351
(17.6828)
|
2.392
(18.8767)
|
4.849
(19.8297)
|
| Week 16: 5 minutes prior to meal (n=24;n=25;n=21) |
5.067
(16.6654)
|
-1.441
(16.3094)
|
13.665
(17.7580)
|
| Title | Change From Baseline in Anti-Intercellular Adhesion Molecule (ICAM) |
|---|---|
| Description | The change in ICAM collected at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 21 |
| Week 4: 5 minutes prior to meal (n=24;n=21; n=19) |
-1.154
(6.7415)
|
-0.294
(7.1785)
|
-23.810
(7.6380)
|
| Week 16: 5 minutes prior to meal (n=24; n=25;n=21) |
-2.495
(8.6653)
|
-4.140
(8.4752)
|
-16.556
(9.3414)
|
| Title | Change From Baseline in e-Selectin |
|---|---|
| Description | The change in e-Selectin collected at each week indicated relative to baseline. |
| Time Frame | Baseline, Week 4 and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 4: 5 minutes prior to meal (n=24;n=21; n=19) |
1.041
(1.3484)
|
0.116
(1.4394)
|
-6.437
(1.5137)
|
| Week 16: 5 minutes prior to meal (n=24; n=25;n=21) |
1.488
(2.0944)
|
-1.671
(2.0480)
|
-4.056
(2.2336)
|
| Title | Change From Baseline in Endothelial Function Through Pulse Wave Tonometry |
|---|---|
| Description | Pulse wave tonometry performed before the meal and 2 hours postmeal using one recording consisting of 15 to 20 sequentially recorded radial artery waveforms collected at each assessment. |
| Time Frame | Baseline and Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Participants who were in the full analysis set and had a baseline and at least 1 post-baseline assessment were included for this analysis. Missing values were imputed using last observation carried forward. |
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. |
| Measure Participants | 24 | 25 | 22 |
| Week 16: pre-meal (n=23;n=23;n=20) |
-3.6
(2.51)
|
-4.7
(2.52)
|
-4.2
(2.68)
|
| Week 16: 2 hours postmeal (n=24;n=24;n=20) |
-1.6
(3.16)
|
0.1
(3.18)
|
-1.3
(3.47)
|
Adverse Events
| Time Frame | Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory values or ECG findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||||
| Arm/Group Title | Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD | |||
| Arm/Group Description | Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. | Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. | |||
All Cause Mortality |
||||||
| Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/24 (0%) | 2/25 (8%) | 3/22 (13.6%) | |||
| Gastrointestinal disorders | ||||||
| Gastric ulcer | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Concussion | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Fall | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Head injury | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Renal and urinary disorders | ||||||
| Nephrolithiasis | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Placebo QD | Alogliptin 25 mg QD | Alogliptin 25 mg QD + Pioglitazone 30 mg QD | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/24 (62.5%) | 19/25 (76%) | 13/22 (59.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/24 (4.2%) | 3/25 (12%) | 0/22 (0%) | |||
| Cardiac disorders | ||||||
| Palpitations | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Eye disorders | ||||||
| Eye irritation | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Eye pruritus | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Gastrointestinal disorders | ||||||
| Constipation | 1/24 (4.2%) | 2/25 (8%) | 2/22 (9.1%) | |||
| Dyspepsia | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Frequent bowel movements | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Nausea | 0/24 (0%) | 1/25 (4%) | 1/22 (4.5%) | |||
| Vomiting | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Abdominal discomfort | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Gastric ulcer | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Gastrooesophageal reflux disease | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Toothache | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| General disorders | ||||||
| Fatigue | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Feeling abnormal | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 1/24 (4.2%) | 5/25 (20%) | 3/22 (13.6%) | |||
| Asymptomatic bacteriuria | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Gastroenteritis | 1/24 (4.2%) | 1/25 (4%) | 0/22 (0%) | |||
| Gastroenteritis viral | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Influenza | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Oral herpes | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Urinary tract infection | 1/24 (4.2%) | 1/25 (4%) | 0/22 (0%) | |||
| Viral infection | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Viral upper respiratory tract infection | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 0/24 (0%) | 0/25 (0%) | 2/22 (9.1%) | |||
| Concussion | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Contusion | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Head injury | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Subcutaneous haematoma | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Wound | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Investigations | ||||||
| Blood potassium decreased | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Blood potassium increased | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Weight decreased | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypoglycaemia | 0/24 (0%) | 0/25 (0%) | 3/22 (13.6%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Myalgia | 1/24 (4.2%) | 0/25 (0%) | 2/22 (9.1%) | |||
| Pain in extremity | 1/24 (4.2%) | 0/25 (0%) | 2/22 (9.1%) | |||
| Arthralgia | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
| Dupuytren's contracture | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Musculoskeletal pain | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 2/24 (8.3%) | 1/25 (4%) | 2/22 (9.1%) | |||
| Hypoaesthesia | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Renal and urinary disorders | ||||||
| Nephrolithiasis | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Oropharyngeal pain | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Blister | 0/24 (0%) | 1/25 (4%) | 0/22 (0%) | |||
| Rash | 1/24 (4.2%) | 0/25 (0%) | 0/22 (0%) | |||
| Vascular disorders | ||||||
| Venous thrombosis limb | 0/24 (0%) | 0/25 (0%) | 1/22 (4.5%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
| Name/Title | Sr. VP, Clinical Science |
|---|---|
| Organization | Takeda Global Research and Development Center, Inc. |
| Phone | 800-778-2860 |
| clinicaltrialregistry@tpna.com |
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT00655863
Other Study ID Numbers:
- SYR-322_301
- 2007-000486-38
- U1111-1113-2081
- NL22649.029.08
First Posted:
Apr 10, 2008
Last Update Posted:
May 27, 2013
Last Verified:
May 1, 2013