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

• Change from Baseline in Fasting Plasma Glucose at Weeks 4, 8, 13 [ Time Frame: Baseline and Weeks 4, 8, and 13 ] [ Designated as safety issue: No ]
• Change from Baseline in Plasma Glucose at Week 13 [ Time Frame: Baseline and Week 13 ] [ Designated as safety issue: No ]
• Cardiovascular and metabolic biomarkers at Baseline and 13 weeks [ Time Frame: Baseline and Week 13 ] [ Designated as safety issue: Yes ]

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.

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.

• Drug: BGP-15 100 mg QD
  Two 50 mg BGP-15 capsules by mouth in the morning; and two Placebo capsules by mouth in the evening
• Drug: BGP-15 100 mg BID
  One 100 mg BGP-15 capsule by mouth in the morning; and one 100 mg BGP-15 capsule by mouth in the evening
• Drug: Placebo BID
  Two Placebo capsules by mouth in the morning; and two Placebo capsules by mouth in the evening
• Drug: BGP-15 200 mg QD
  Two 100 mg BGP-15 capsule by mouth in the morning; and two Placebo capsule by mouth in the evening
• Drug: BGP-15 200 mg BID
  Two 100 mg BGP-15 capsules by mouth in the morning; and two 100 mg BGP-15 capsules by mouth in the evening
• Drug: BGP-15 400 mg QD
  Two 200 mg BGP-15 capsules by mouth in the morning; and two Placebo capsules by mouth in the evening

• Experimental: 6. BGP-15
  400 mg BGP-15 + Placebo
  Intervention: Drug: BGP-15 400 mg QD
• Experimental: 5. BGP-15
  200 mg BGP-15 BID
  Intervention: Drug: BGP-15 200 mg BID
• Experimental: 4. BGP-15
  200 mg BGP-15 + Placebo
  Intervention: Drug: BGP-15 200 mg QD
• Experimental: 3. BGP-15
  Two 50 mg BGP-15 capsules by mouth in the morning; and two 50 mg BGP-15 capsules by mouth in the evening
  Intervention: Drug: BGP-15 100 mg BID
• Experimental: 2. BGP-15
  100 mg BGP-15 + placebo
  Intervention: Drug: BGP-15 100 mg QD
• Experimental: 1. Placebo
  Placebo BID
  Intervention: Drug: Placebo BID

Inclusion criteria

Patients meeting all of the following criteria will be eligible for enrollment:

1. Male and female patients with T2DM at time of diagnosis as defined by the American Diabetes Association (ADA) criteria;
2. Age between 30 and 70 years (inclusive);
3. HbA1c ≥7.5% - ≤12.0% at Screening, Visit 1;
4. FPG ≤270 mg/dL (15.0 mmol/L);
5. Body mass index (BMI) >27 and ≤40 kg/m2;
6. 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;

7. Women may be enrolled if all three of the following criteria are met:

   1. They have a negative serum pregnancy test at Screening;
   2. They are not breast feeding; and,
   3. 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;

8. Willingness to sign an informed consent document; and,
9. 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:

1. Treatment with peroxisome proliferator-activated receptor (PPAR) agonists (including fibrates) within the last 3 months;
2. Treatment with dipeptidyl peptidase 4 (DPP-4) inhibitors, acarbose, or incretins within the last 3 months;
3. Chronic use of insulin injections within the last 1 month;
4. Hypoglycemia requiring third party assistance within the last 3 months;
5. Impaired hepatic function measured as alanine aminotransferase (ALAT) >2X the upper reference limit;
6. Impaired renal function measured as serum creatinine >150 umol/L (1.7 mg/dL);
7. Decompensated heart failure (New York Heart Association [NYHA] class III and IV);
8. Unstable angina pectoris or myocardial infarction within the last 12 months;
9. Clinically significant ECG abnormalities at screening including QTc interval (Bazett's) ≥450 msec or AV block >1st degree;
10. Uncontrolled, treated or untreated hypertension (systolic blood pressure [BP] ≥160 mmHg and/or diastolic BP ≥100 mmHg);
11. 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;
12. Pregnancy or breastfeeding, the intention to become pregnant, or judged to be using inadequate contraceptive measures;
13. History of alcohol and/or drug dependence within the last 2 years;
14. Receipt of any investigational drug or medical device within 3 months prior to this trial;
15. Fasting triglycerides >700 mg/dL at screening; or,
16. Diagnosis or treatment of cancer within the past 5 years except for excision of basal cell or squamous cell skin lesions.

• Integrium
• Msource Medical Development GmbH
• Kinexum LLC
• Thermo Fisher Scientific
• Haupt Pharma Wülfing GmbH
• BARC nv