A Clinical Trial to Study the Efficacy, Safety, Tolerability and Pharmacokinetics of P2202 in Patients of Type 2 Diabetes

Study Overview
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Brief Summary
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It is a phase II, randomized, double-blind, placebo-controlled study of P2202 in patients of type 2 diabetes mellitus, inadequately controlled with a stable dose of metformin or sulfonylurea or both.

Detailed Description
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It is a phase II, prospective, randomized, double-blind, placebo-controlled, dose-ranging, multi-centre, two-staged, fixed-design study of P2202 in patients of type 2 diabetes mellitus, inadequately controlled with a stable dose of metformin or sulfonylurea or both. This study will consist of accrual in Stage I (n=56/arm, which is 70% of the total sample size required), followed by an interim analysis on completion of the treatment period, to aid further decisions on accrual and dose selection in Stage II of the study, and completion of Stage I.

Official Title
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A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Two-staged, Fixed Design Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of P2202 in Overweight/Obese Patients of Type 2 Diabetes Mellitus Inadequately Controlled on Metformin, Sulphonylurea, or Both.

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: P2202
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who understand and are willing to give informed consent to participate in the trial. Adult male and female subjects between 18 years to 65 years of age with a BMI ≥ 27 kg/m2 ≤ 40 kg/m2, inclusively. Subjects with established type 2 diabetes mellitus of at least 3 months duration at the time of screening. Subjects with an inadequate glycemic control defined by an HbA1c level of ≥ 7.5% and ≥10% at screening. Subjects who are on a stable dose of: Metformin (up to 2.55 gm/day or maximum tolerated dose of at least 1 gm/day) and/or Sulfonylurea (glimepiride ≤ 4 mg/day, gliclazide ≤ 160 mg, glibenclamide or glyburide ≤ 10 mg and glipizide ≤ 10 mg), for ≤ 2 months prior to the screening visit. Subjects with fasting plasma glucose of ≤14.4 mmol/L (260 mg/dL) and at least 5.5 mmol/L or 100 mg/dL. Exclusion Criteria: Subjects who have type 1 diabetes mellitus, maturity-onset diabetes of the young or any rare form of diabetes. Subjects with hyperglycemia due to secondary causes. Subjects who have had more than 4 episodes of severe hypoglycemia in the 6 months prior to screening. Subjects with a history of acute diabetic complications Subjects who have been treated with insulin (except for use of insulin for short term management of acute conditions), thiazolidinediones, dual proliferator activated receptors agonists, glucagon-like peptide analogues, dipeptidyl peptidase inhibitors or 11bHSD-1 inhibitors in any form, in the 3 months prior to screening. Subjects who are receiving systemic glucocorticoids (≥14 days)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: P2202<br>Two treatment arms in Stage I- P2202 (1000 mg) and placebo Four treatment arms in stage II- P2202 (suggested dose levels 750 mg, 500 mg or 250 mg) or placebo | Drug: P2202<br>* Novel oral drug with potent and selective 11 beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) inhibitory properties, being developed for the management of type 2 diabetes mellitus<br>|
| Placebo Comparator: Placebo<br>Two treatment arms in Stage I- P2202 (1000 mg) and placebo Four treatment arms in stage II- P2202 (suggested dose levels 750 mg, 500 mg or 250 mg) or placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c from baseline | The change in HbA1c from baseline till end of 12 weeks in patients of type 2 diabetes mellitus, in the P2202 arms as compared to placebo. | From baseline till end of 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events | Safety assessment will be done by eliciting information regarding AEs including evaluation of hypoglycemic events, physical examination, vital signs assessment, 12-lead ECGs, clinical laboratory tests, markers of HPA axis function, plasma ACTH and free testosterone, plasma rennin and serum aldosterone and self-monitoring of blood glucose profiles. | From screening to 3 weeks (± 1 week) after the last visit at the end of Week 12 or early exit visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus