The objective of the study is to evaluate the efficacy of the addition of SYR-322 (25 mg) to subjects who are inadequately controlled on pioglitazone HCl (30 mg) and metformin (*1500 mg or MTD).
ID
Source
Brief title
Condition
- Diabetic complications
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to evaluate the efficacy of the addition
of SYR-322 (25 mg) versus the titration of pioglitazone HCl from 30 to 45 mg on
glycemic control (HbA1c) at Week 26 and Week 52.
Secondary outcome
The secondary objectives of this study are to determine the effect of treatment
with SYR-322 versus titration of pioglitazone HCl from 30 mg to 45 mg on the
change from Baseline (Day 1) HbA1c at all visits except Week 26 and Week 52,
fasting plasma glucose, proinsulin, insulin, C-peptide, serum lipids, NMR lipid
fractionation, free fatty acids, apolipoprotein A-I, A-II, B, C-III, PAI-1,
hsCRP, adiponectin, body weight, homeostatic model assessment (HOMA) insulin
resistance, HOMA beta-cell function, incidence of marked hyperglycemia (fasting
plasma glucose *200 mg/dL [11.10 mmol/L]), incidence of rescue from study, QOL
and pharmacoeconomic assessments and to evaluate the safety of SYR-322 versus
titration of pioglitazone HCl on AEs, clinical laboratory parameters,
electrocardiogram (ECG) readings, physical examinations, and hypoglycemic
events.
Background summary
SYR-322 is a potent, selective, orally available inhibitor of dipeptidyl
peptidase IV
(DPP-IV) that is currently being developed by Takeda Global Research &
Development Center, Inc. (TGRD) as a treatment for type 2 diabetes mellitus
(DM2). DPP-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 (GLP-1) and glucose-dependent insulinotropic peptide
(GIP). Both peptides exert important effects on islet *-cells to stimulate
glucose-dependent insulin secretion and regulate *-cell proliferation and
cytoprotection. GLP-1 also inhibits gastric emptying, glucagon secretion, and
food intake.
The glucose-lowering actions of GLP-1, but not GIP, are preserved in patients
with DM2. Therefore, by selectively inhibiting the enzymatic activity of DPP-IV
and thereby increasing plasma GLP-1 levels, SYR-322 shows promise as a novel
agent for the treatment of DM2.
Study objective
The objective of the study is to evaluate the efficacy of the addition of
SYR-322 (25 mg) to subjects who are inadequately controlled on pioglitazone HCl
(30 mg) and metformin (*1500 mg or MTD).
Study design
This is an international, multicenter, randomized, double-blind, 2-treatment
arm study. The study is to be conducted in at least 760 subjects with type 2
diabetes who are experiencing inadequate glycemic control on a current regimen
of metformin (*1500 mg or maximum tolerated dose [MTD]) plus pioglitazone HCl
(30 mg).
Subjects who are experiencing inadequate glycemic control (defined as an HbA1c
between 7.0-10.0%) while on a treatment regimen of metformin (*1500 mg or MTD)
plus pioglitazone HCl (30 mg) will immediately go into a screening period of up
to 2-weeks, a 4-week stabilization period, a 52-week double-blind treatment
period, followed by an End-of-Treatment visit and a 2-week follow-up visit. The
duration of the study will be approximately 60 weeks for these subjects.
Subject who are experiencing inadequate glycemic control (defined as an HbA1c
>8.0%) who are on a combination therapy including metformin and another oral
antidiabetic agent (ie, sulfonylureas, rosiglitazone maleate, or pioglitazone
HCl 15 mg, etc.) will enter into a pre-screening period of 2-weeks. These
subjects will be instructed to discontinue their previous combination therapy
and immediately start a regimen consisting of *1500 mg metformin (or MTD) and
pioglitazone 30 mg. The subjects will undergo a 12-week period following this
switch in treatment and then return for a 2-week screening period to assess
their glycemic control. If the subject has an HbA1c between 7.0-10.0% they will
enter into a 4-week stabilization period, a 52-week double-blind treatment
period, followed by an End-of Treatment visit and a 2-week follow-up visit. The
duration of the study will be approximately 74 weeks for these subjects.
Subjects will be randomly assigned to 1 of 2 treatment groups in a 1:1 ratio as
follows: addition of SYR-322 25 mg versus titration of pioglitazone HCl from 30
mg to 45 mg.
Intervention
N/A
Study burden and risks
BURDEN
Questionnaires: 3x
Interviews: At visits - Depending on the group in which the patient is
randomized, 17x to 19x
Physical/psychological examination:
Complete physical examination: Depending on the group in which the patient is
randomized, 3x to 4x
Brief physical examination: 3x
Clinical examination of skin and digits: Depending on the group in which the
patient is randomized, 17x to 18x
Determination of lenght, BMI: Depending on the group in which the patient is
randomized, 1x to 2x
Body weight: Depending on the group in which the patient is randomized, 8x to 9x
Blood pressure: Depending on the group in which the patient is randomized, 17x
to 19x
Hartfrequency: Depending on the group in which the patient is randomized, 17x
to 19x
Oral temperature: Depending on the group in which the patient is randomized, 8x
to 9x
Overnight fast: Depending on the group in which the patient is randomized, 13x
to 14x
Diabetes educatie: 9x
RISKS
Blood extraction:
Failed attempts
Pain and rubor
Extravasation of blood
Feeling of lightheadedness and/or fainting
Infection
Glucosemeter:
Pain and extravasation of blood at puncture site
Electrode stickers:
Skin irritation
2 Arundel Street
Arundel Great Court; London, WC2R 3DA
GB
2 Arundel Street
Arundel Great Court; London, WC2R 3DA
GB
Listed location countries
Age
Inclusion criteria
Subject eligibility is determined based on the following criteria at Pre-Screening (if applicable) and Screening:
1. Males or females, aged 18-80 years of age, inclusive, with a historical diagnosis of type 2 diabetes.
2. The subjects must meet one of the following:
A. The subject has been inadequately controlled on a stable dose of *1500 mg (or MTD) of metformin and 30 mg of pioglitazone HCl for at least 2 months prior to Screening. Inadequate glycemic control is defined as an HbA1c concentration between 7.0 and 10.0%, inclusive stable dose of *1500 mg (or MTD) of metformin plus 30 mg of pioglitazone HCl. After completing the Screening visit, these subjects will immediately enter stabilization according to Study Schedule A (Fig. 6.a and Appendix A).
B. The subject has been inadequately controlled (as defined by an HbA1c >8.0%) on a combination therapy including metformin and another oral antidiabetic agent (ie, sulfonylureas, rosiglitazone maleate, or pioglitazone HCl 15 mg, etc.). After completing the Pre-Screening visit, these subjects will discontinue this previous combination therapy and will be switched to a stable dose of *1500 mg (or MTD) of metformin and 30 mg of pioglitazone HCl for a 12-week period according to Study Schedule B (Fig. 6.b and Appendix A). Following this 12-week period, the subject must qualify for entry into the stabilization period by completing the Screening visit.
3. The subject has a body mass index >23 kg/m2 and <45 kg/m2.
Exclusion criteria
Any subject who meets any of the following criteria at Pre-Screening (if applicable) and Screening will not qualify for entry into the study:
1. The subject has a urine albumin/creatinine ratio of >1000 µg/mg (113 mg/mmol).
2. The subject has a history of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
3. The subject has had gastric bypass surgery.
4. The subject has New York Heart Association Class III or IV heart failure regardless of therapy.
Currently treated subjects who are stable at Class I or II are candidates for the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clintrials.gov |
| EudraCT | EUCTR2006-006025-73-NL |
| CCMO | NL16609.015.07 |