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

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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: BGP-15 400 mg QD; Drug: BGP-15 200 mg BID; Drug: BGP-15 200 mg QD; Drug: BGP-15 100 mg BID; Drug: BGP-15 100 mg QD; Drug: Placebo BID

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bad Mergentheim, Germany, 97980
    • Diabetespraxis Bad Mergentheim
  • Großheirath-Rossach, Germany, 96269
    • Praxis Dr. Schätzl
  • Köln, Germany, 50937
    • Universitätsklinikum Köln
  • Neuwied, Germany, 56564
    • Schwerpunktpraxis Diabetes
  • Siegen, Germany, 57072
    • Diabetologische Schwerpunktpraxis
• Hungary
  • Balatonfüred, Hungary, 8230
    • DRUG Research Center Hungary Kft.
  • Budapest, Hungary, 1088
    • Semmelweis University 2nd Clinic for Internal Medicine
  • Győr, Hungary, 9024
    • Petz Aladar Country Teaching Hospital, Dept of Diabetology and Metabolism
  • Szentes, Hungary, 6600
    • Dr. Bugyi Istvan Hospital, Diabetology Outpatient Clinic
  • Zalaegerszeg, Hungary, 8900
    • Zala County Hospital Department of Diabetology
• United States
  • California
    • Los Angeles, California, United States, 90057
      • Andrew J. Lewin Medical Corporation DBA National Research Institute
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC.
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Colorado
    • Denver, Colorado, United States, 80209
      • Creekside Endocrine Associates PC
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute, Inc.
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta Pharmaceutical Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • ICCT Research International, Inc.
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • MedStar Health Research Institute
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research, P.C.
  • Nevada
    • Las Vegas, Nevada, United States, 89101
      • Nevada Alliance Against Diabetes
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • New Hanover Medical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research, LLC.
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Upstate Pharmaceutical Research
    • Greer, South Carolina, United States, 29651
      • Mountain View Clinical Research
    • Taylors, South Carolina, United States, 29687
      • Southeastern Research Associates, Inc.
  • Tennessee
    • Athens, Tennessee, United States, 37303
      • Athens Medical Group
  • Texas
    • Houston, Texas, United States, 77074
      • Juno Research, LLC.
    • Katy, Texas, United States, 77451
      • Juno Research, LLC.
    • San Antonio, Texas, United States, 78229
      • Cetero Research-San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 6. BGP-15; 400 mg BGP-15 + Placebo	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: 5. BGP-15; 200 mg BGP-15 BID	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
Experimental: 4. BGP-15; 200 mg BGP-15 + Placebo	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
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	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
Experimental: 2. BGP-15; 100 mg BGP-15 + placebo	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
Experimental: 1. Placebo; Placebo BID	Drug: Placebo BID; Two Placebo capsules by mouth in the morning; and two Placebo capsules by mouth in the evening

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: N-Gene Research Laboratories, Inc.
• Collaborators: Thermo Fisher Scientific, Inc; Integrium; Msource Medical Development GmbH; Kinexum LLC; Haupt Pharma Wülfing GmbH; Barc NV
• Investigators: Study Director: Peter Damsbo, MD, Kinexum LLC, Harper's Ferry, WV, USA; Principal Investigator: Robert Ratner, MD, Medstar Research Institute, Hyattsville, Maryland, USA; Principal Investigator: Ioanna Gouni-Berthold, MD, University of Cologne; Principal Investigator: Laszlo Koranyi, MD, Drug Research Center, Balatonfured, Hungary

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: February 16, 2010
• First Submitted That Met QC Criteria: February 16, 2010
• First Posted (Estimate): February 17, 2010

Study Record Updates

• Last Update Posted (Estimate): September 29, 2014
• Last Update Submitted That Met QC Criteria: September 26, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Type 2
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; BGP 15
• Other Study ID Numbers: BGP-15-CLIN-IR04; 2009-013328-21 (EudraCT Number)