Safety and Efficacy of BGP-15 in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a safety and dose finding efficacy study to evaluate the effects of BGP-15 over the dose range of 100 mg/day to 400 mg/day. Doses are applied once or twice a day for 13 weeks as add-on therapy to the combination of metformin and sulfonylurea treatment or metformin alone in patients with Type 2 Diabetes Mellitus.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, parallel group, multiple dose, multicenter study with 5 treatment arms and 1 placebo arm. Patients should be treated with both metformin and SU or metformin alone. Patients will be randomized to 100,100 + 100, 200, 200 + 200, and 400 mg/day or placebo, as an add-on to their current treatment. The study consists of 2 periods: A 14-day screening period for ascertaining the inclusion/exclusion criteria; and, A 13-week treatment period with different doses of BGP-15 or placebo as an add-on therapy to metformin and SU treatment or metformin treatment alone.

Official Title
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Randomized, Double-blind, Placebo-controlled, Parallel Group, Multiple Dose, Multicenter Study to Assess Safety & Efficacy of BGP-15 Administered Orally 1 or 2 Times Daily With Metformin & Sulfonylurea or Metformin in T2 Diabetic Patients

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: BGP-15 100 mg QD
* Drug: BGP-15 100 mg BID
* Drug: Placebo BID
* Drug: BGP-15 200 mg QD
* Drug: BGP-15 200 mg BID
* Drug: BGP-15 400 mg QD


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients meeting all of the following criteria will be eligible for enrollment: Male and female patients with T2DM at time of diagnosis as defined by the American Diabetes Association (ADA) criteria; Age between 30 and 70 years (inclusive); HbA1c ≥7.5% - ≤12.0% at Screening, Visit 1; FPG ≤270 mg/dL (15.0 mmol/L); Body mass index (BMI) >27 and ≤40 kg/m2; Current treatment with either metformin alone or in combination with SU. The dose of the current treatment must be stable for at least 8 weeks prior to randomization. Patients being treated with metformin must be at their optimal or near-optimal dose (≥1500 mg/day ± 500 mg/day for a range of 1000 to 2000 mg/day), and patients being treated with SU must be receiving at least one half of the maximum approved SU dose; Women may be enrolled if all three of the following criteria are met: They have a negative serum pregnancy test at Screening; They are not breast feeding; and, They do not plan to become pregnant during the study AND if one of the following three criteria is met: i. They have had a hysterectomy or tubal ligation at least 6 months prior to signing the informed consent form; ii. They have been postmenopausal for at least 1 year; or, iii. They are of childbearing potential and will practice one of the following methods of birth control throughout the study: injectable or implantable hormonal contraception or intrauterine device; or two of the following methods of birth control throughout the study: oral or patch contraception plus a barrier contraceptive (eg, diaphragm plus spermicide, male or female condom plus spermicide, or vasectomized male partner). Abstinence, partner's use of condoms, and vasectomy are NOT acceptable methods of contraception; Willingness to sign an informed consent document; and, No conditions that hinder participation in the trial, as determined by the Investigator and Sponsor. Exclusion criteria Patients meeting any of the following criteria will be ineligible for enrollment: Treatment with peroxisome proliferator-activated receptor (PPAR) agonists (including fibrates) within the last 3 months; Treatment with dipeptidyl peptidase 4 (DPP-4) inhibitors, acarbose, or incretins within the last 3 months; Chronic use of insulin injections within the last 1 month; Hypoglycemia requiring third party assistance within the last 3 months; Impaired hepatic function measured as alanine aminotransferase (ALAT) >2X the upper reference limit; Impaired renal function measured as serum creatinine >150 umol/L (1.7 mg/dL); Decompensated heart failure (New York Heart Association [NYHA] class III and IV); Unstable angina pectoris or myocardial infarction within the last 12 months; Clinically significant ECG abnormalities at screening including QTc interval (Bazett's) ≥450 msec or AV block >1st degree; Uncontrolled, treated or untreated hypertension (systolic blood pressure [BP] ≥160 mmHg and/or diastolic BP ≥100 mmHg); Any condition that the Investigator and/or Sponsor feel would interfere with trial participation or evaluation of the results eg, drug abuse or serious disease such as acquired immunodeficiency syndrome/human immunodeficiency syndrome (AIDS/HIV) antibodies, Hepatitis B, or Hepatitis C; Pregnancy or breastfeeding, the intention to become pregnant, or judged to be using inadequate contraceptive measures; History of alcohol and/or drug dependence within the last 2 years; Receipt of any investigational drug or medical device within 3 months prior to this trial; Fasting triglycerides >700 mg/dL at screening; or, Diagnosis or treatment of cancer within the past 5 years except for excision of basal cell or squamous cell skin lesions.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: 6. BGP-15<br>400 mg BGP-15 + Placebo | Drug: BGP-15 400 mg QD<br>* Two 200 mg BGP-15 capsules by mouth in the morning; and two Placebo capsules by mouth in the evening<br>|
| Experimental: 5. BGP-15<br>200 mg BGP-15 BID | Drug: BGP-15 200 mg BID<br>* Two 100 mg BGP-15 capsules by mouth in the morning; and two 100 mg BGP-15 capsules by mouth in the evening<br>|
| Experimental: 4. BGP-15<br>200 mg BGP-15 + Placebo | Drug: BGP-15 200 mg QD<br>* Two 100 mg BGP-15 capsule by mouth in the morning; and two Placebo capsule by mouth in the evening<br>|
| Experimental: 3. BGP-15<br>Two 50 mg BGP-15 capsules by mouth in the morning; and two 50 mg BGP-15 capsules by mouth in the evening | Drug: BGP-15 100 mg BID<br>* One 100 mg BGP-15 capsule by mouth in the morning; and one 100 mg BGP-15 capsule by mouth in the evening<br>|
| Experimental: 2. BGP-15<br>100 mg BGP-15 + placebo | Drug: BGP-15 100 mg QD<br>* Two 50 mg BGP-15 capsules by mouth in the morning; and two Placebo capsules by mouth in the evening<br>|
| Experimental: 1. Placebo<br>Placebo BID | Drug: Placebo BID<br>* Two Placebo capsules by mouth in the morning; and two Placebo capsules by mouth in the evening<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Glycosylated Hemoglobin at Week 13 |  | Baseline and Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Fasting Plasma Glucose at Weeks 4, 8, 13 |  | Baseline and Weeks 4, 8, and 13 | 
| Change from Baseline in Plasma Glucose at Week 13 |  | Baseline and Week 13 | 
| Cardiovascular and metabolic biomarkers at Baseline and 13 weeks |  | Baseline and Week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2