Clinical trial NCT01069965: Safety and Efficacy of BGP-15 in Patients With Type 2 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diabetes Mellitus
Keywords: Type 2
Lead sponsor: N-Gene Research Laboratories, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Integrium
name: Msource Medical Development GmbH
name: Kinexum LLC
name: Thermo Fisher Scientific, Inc
name: Haupt Pharma Wülfing GmbH
name: Barc NV
First posted: 2010-02-17
Enrollment: 196
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in Glycosylated Hemoglobin at Week 13
timeFrame: Baseline and Week 13
Secondary outcomes:
measure: Change from Baseline in Fasting Plasma Glucose at Weeks 4, 8, 13
timeFrame: Baseline and Weeks 4, 8, and 13
measure: Change from Baseline in Plasma Glucose at Week 13
timeFrame: Baseline and Week 13
measure: Cardiovascular and metabolic biomarkers at Baseline and 13 weeks
timeFrame: Baseline and Week 13
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Andrew J. Lewin Medical Corporation DBA National Research Institute
state: California
city: Paramount
country: United States
facility: Center for Clinical Trials, LLC.
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Denver
country: United States
facility: Creekside Endocrine Associates PC
state: Colorado
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute, Inc.
state: Florida
city: Decatur
country: United States
facility: Atlanta Pharmaceutical Research
state: Georgia
city: Chicago
country: United States
facility: ICCT Research International, Inc.
state: Illinois
city: Hyattsville
country: United States
facility: Medstar Health Research Institute
state: Maryland
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research, P.C.
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Alliance Against Diabetes
state: Nevada
city: Wilmington
country: United States
facility: New Hanover Medical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research, LLC.
state: North Carolina
city: Greenville
country: United States
facility: Upstate Pharmaceutical Research
state: South Carolina
city: Greer
country: United States
facility: Mountain View Clinical Research
state: South Carolina
city: Taylors
country: United States
facility: Southeastern Research Associates, Inc.
state: South Carolina
city: Athens
country: United States
facility: Athens Medical Group
state: Tennessee
city: Houston
country: United States
facility: Juno Research, LLC.
state: Texas
city: Katy
country: United States
facility: Juno Research, LLC.
state: Texas
city: San Antonio
country: United States
facility: Cetero Research-San Antonio
state: Texas
city: Bad Mergentheim
country: Germany
facility: Diabetespraxis Bad Mergentheim
city: Großheirath-Rossach
country: Germany
facility: Praxis Dr. Schätzl
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Neuwied
country: Germany
facility: Schwerpunktpraxis Diabetes
city: Siegen
country: Germany
facility: Diabetologische Schwerpunktpraxis
city: Balatonfüred
country: Hungary
facility: DRUG Research Center Hungary Kft.
city: Budapest
country: Hungary
facility: Semmelweis University 2nd Clinic for Internal Medicine
city: Győr
country: Hungary
facility: Petz Aladar Country Teaching Hospital, Dept of Diabetology and Metabolism
city: Szentes
country: Hungary
facility: Dr. Bugyi Istvan Hospital, Diabetology Outpatient Clinic
city: Zalaegerszeg
country: Hungary
facility: Zala County Hospital Department of Diabetology
Study officials:
affiliation: Kinexum LLC, Harper's Ferry, WV, USA
name: Peter Damsbo, MD
role: STUDY_DIRECTOR
affiliation: Medstar Research Institute, Hyattsville, Maryland, USA
name: Robert Ratner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cologne
name: Ioanna Gouni-Berthold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Drug Research Center, Balatonfured, Hungary
name: Laszlo Koranyi, MD
role: PRINCIPAL_INVESTIGATOR
References: