A Placebo Controlled Safety and Efficacy Study of INT131 Besylate in Type 2 Diabetes, With an Active Comparator

Study Overview
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Brief Summary
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This is a 24 week study comparing the efficacy of four dose levels of INT131 besylate with pioglitazone HCl in patients with type 2 diabetes. Eligible patients will be men and women (of non-childbearing potential or using dual barrier methods of contraception) between 30 and 75 years of age who are minimally responsive to treatment with sulfonylurea monotherapy or sulfonylurea plus metformin combination therapy.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, 24-Week Study to Evaluate the Efficacy and Safety of INT131 Besylate Compared to Pioglitazone in Subjects With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: INT131 besylate
* Drug: Pioglitazone HCl
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Type 2 diabetes and on either sulfonylurea monotherapy or sulfonylurea plus metformin combination therapy for at least 3 months at stable dose Males and Females (of non-childbearing potential or who are using dual barrier methods of contraception) between 30 and 75 years of age HbA1c must be ≥7.5% and ≤10% at screening Fasting Plasma Glucose must be <240 mg/dL at screening Exclusion Criteria: History of type 1 diabetes History of diabetic ketoacidosis NYHA Class III or IV cardiac status or hospitalization for congestive heart failure within 6 weeks prior to Visit 1 Treatment with any non-peroxisome proliferator-activated receptor (non-PPAR) antidiabetic agent, investigational or approved, other than metformin or permitted sulfonylureas within 3 months prior to screening Treatment with rosiglitazone, pioglitazone, or any PPAR investigational antidiabetic agent within 6 month prior to screening Body mass index >45 kg/m2 Fasting triglycerides >500 mg/dL Uncontrolled hypertension (sitting systolic blood pressure >160 mmHg and/or sitting diastolic blood pressure >100 mmHg Presence of diabetic complications, which in the opinion of the investigator, would complicate the subject's participation in the study (i.e., require initiation of new medication)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INT131 besylate 0.5 mg<br>INT131 besylate 0.5 mg once-daily administration and matching placebo to pioglitazone HCl. | Drug: INT131 besylate<br>* Once-daily, oral<br>|
| Experimental: INT131 besylate 1 mg<br>INT131 besylate 1 mg once-daily administration and matching placebo to pioglitazone HCl | Drug: INT131 besylate<br>* Once-daily, oral<br>|
| Experimental: INT131 besylate 2 mg<br>INT131 besylate 2 mg administered once-daily and matching placebo to pioglitazone HCl | Drug: INT131 besylate<br>* Once-daily, oral<br>|
| Experimental: INT131 besylate 3 mg<br>INT131 besylate 3 mg administered once-daily and matching placebo to pioglitazone HCl | Drug: INT131 besylate<br>* Once-daily, oral<br>|
| Active Comparator: pioglitazone HCl 45 mg<br>pioglitazone HCl 45 mg administered once-daily and matching placebo to INT131 besylate | Drug: Pioglitazone HCl<br>* Once-daily, oral<br>* Other names: Actos;|
| Placebo Comparator: placebo<br>placebo administered once-daily, matching placebo to INT131 besylate and matching placebo to pioglitazone HCl | Drug: Placebo<br>* Once-daily, oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward | HbA1c is measured as percent. Thus this change from baseline reflects the week 24 HbA1c percent minus the Week 0 HbA1c percent | Weeks 0-24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward. | The change from baseline reflects the Week 24 FPG minus the Week 0 FPG with last observation carried forward. | Weeks 0-24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes, diabetes, diabetes mellitus, diabetes mellitus, type 2, non-TZD, thiazolidinedione, selective peroxisome proliferator-activated receptor gamma modulator, SPPARM, peroxisome proliferator-activated receptor gamma, PPAR gamma, insulin sensitizer, glucose control, endocrinopathy, hypoglycemic agent, sulfonylurea, metformin, pioglitazone, nutritional and metabolic diseases