E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with an established diagnosis of Type 2 Diabetes Mellitus (T2DM) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | Diabetes mellitus |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the glycosylated hemoglobin (HbA1c) treatment effects of BGP-15 over the dose range of 100 mg/day to 400 mg/day given as 100, 100 + 100, 200, 200 + 200, and 400 mg/day in patients with type 2 diabetes mellitus (T2DM) treated with metformin alone or in combination with sulfonylurea (SU). |
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E.2.2 | Secondary objectives of the trial |
To compare BGP-15 and placebo with regard to: • Evaluation of safety profile • Glucose-lowering effect of BGP-15 administered at doses of 100, 100 + 100, 200, 200 + 200, and 400 mg/day • Fasting glucose (before breakfast and after at least 8 hours of fasting) at Baseline and following 4 weeks, 8 weeks, and 13 weeks of treatment; • Home monitored glucose values obtained from 7-point profile; • Insulin (AUC) and C-peptide (AUC) after a mixed-meal stimulation at Baseline and following 13 weeks of treatment; and,
• US sites only: Pharmacokinetics (PK) following 13 weeks of BGP 15 treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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% - ≤10.0% 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 maybe enrolled if the following criteria are met: a. They have a negative serum pregnancy test at Screening; b. They are not breast feeding; and, c. They have had a hysterectomy or bilateral tubal ligation at least 6 months prior to signing the informed consent form; or, d. They have been postmenopausal for at least 1 year; 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.
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E.4 | Principal exclusion criteria |
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 µmol/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; 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. 17. Patients treated with metformin with one of the following conditions: a. Renal disease or renal dysfunction (eg, as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (see WARNINGS and PRECAUTIONS). b. Known hypersensitivity to metformin hydrochloride. c. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin; 18. Patients treated with sulfonylurea with one of the following conditions: a. Known hypersensitivity or allergy to the drug; b. Diabetic ketoacidosis, with or without coma. This condition should be treated with insulin; c. Type I diabetes mellitus, as sole therapy; or, 19. Patients unable to give informed consent.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is change in glycated hemoglobin (HbA1c) from baseline to Week 13 post-randomization. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |