A Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SLV337 in Patients with Type 2 Diabetes on Metformin Monotherapy

Conditions: Type 2 diabetes mellitus (T2DM)
MedDRA version: 12.0Level: LLTClassification code 10067585Term: <Manually entered code. Term in E.1.1>

Registration Number: EUCTR2009-011589-27-BG

Lead Sponsor: aboratoires Fournier S.A. A Solvay Pharmaceuticals company

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 56

Inclusion Criteria

1. Male or female of non-childbearing potential, aged 18 to 75 years inclusive.
2. Diagnosed with T2DM defined by the American Diabetes Association criteria: FPG
=7.0 mmol/L (126 mg/dL), or two hours postprandial glucose =11.1 mmol/L
(200 mg/dL).
3. Treated with life style modification and stable dose of metformin monotherapy, =850 mg daily dose, for at least three months; the dose of metformin, physical exercise and dietary recommendations will stay unchanged during the whole duration of the study.
4. With inadequate glycemic control, defined by hemoglobin A1c (HbA1c) =7%, but <10%.
5. With FPG <15 mmol/L (270 mg/dl).
6. If female, the subject should be of non-childbearing potential, defined as being
post-menopausal for at least 24 months prior to dosing (with confirmed estradiol
=20 pg/mL [73 pmol/L] and follicle-stimulating hormone =40 mIU/mL) at Screening if
less than 60 years old, or surgically sterilized (with negative pregnancy test at Screening in the absence of hysterectomy). If male, unless the subject has undergone a vasectomy, he must abstain from sexual contact with women who may become pregnant, or use a combination of a condom and spermicide as a contraception measure from the first dosing up to three months after the last intake of study drug.
7. Subjects will have given their voluntary written informed consent to participate in the study in their own language and be willing to comply with the protocol. Consent will be documented by the subject’s name and dated signature prior to screening procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Type 1 diabetes mellitus, maturity onset diabetes of the young.
2. C-peptide <0.27 nmol/L (0.8 ng/mL).
3. Currently treated or treated during the last three months with insulin therapy.
4. Ongoing oral dual anti-diabetic therapy or treated during the last three months by oral anti-diabetic therapy other than metformin.
5. Treatment with a fibrate, ezetimibe or with any lipid lowering agents other than statins.
6. Treatment with warfarin and other coumarinic derivatives (i.e. acenocoumarol).
7. Body mass index >40.0 kg/m2.
8. Uncontrolled arterial hypertension defined by systolic blood pressure (SBP) =160 and/or diastolic blood pressure (DBP) =95 mmHg taken in a semi-recumbent position, after 5 minutes rest.
9. Renal failure or renal dysfunction defined by creatinine clearance <60 mL/min as
calculated with the Modification of Diet in Renal Disease formula as follows:eGFR (mL/min/1.73m2)= 175 x [SerumCreatinine(µmol/L) x 0.0113]-1.154
x Age(years)-0.203 (x 0.742 if female). For African-Americans the value should be
multiplied by 1.21.
Note: values <60 mL/min are likely to deviate from the true value.
10. History of proliferative retinopathy or maculopathy requiring, or previously treated with, laser therapy.
11. Evidence of unstable cardiovascular diseases: 1) coronary bypass surgery, or angioplasty within three months of the screening visit; 2) myocardial infarction, unstable angina pectoris or other significant cardiac event (including history of cardiac arrhythmias or conduction delays on electrocardiogram [ECG]) or cerebral stroke within three months of the screening visit; 3) severe peripheral artery disease as evidenced by intermittent claudication within three months of the screening visit; 4) peripheral artery surgery within three months of the screening visit.
12. Heart failure New York Heart Association class I to IV.
13. History of pancreatitis or gall bladder disease, with the exception of subjects with gall bladder disease who have previously undergone a cholecystectomy.
14. History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption.
15. History of gastric or duodenal ulcer within three months of the screening visit.
16. History of diagnosis of hepatitis B or hepatitis C.
17. History of solid organ transplant.
18. History of diagnosed hereditary or acquired myopathy.
19. History of mental instability, drug or alcohol abuse or subject who was treated for severe psychiatric illness, which, in the opinion of the Investigator, may interfere with optimal participation in the study.
20. History of cancer (except basal cell carcinoma or squamous cell skin cancer).
21. Evidence of other relevant diseases not related to T2DM as revealed by history, physical examination and laboratory assessments which are deemed to limit study evaluation or participation in the judgment of the Investigator.
22. Alanine aminotransferase (ALT) = two times upper limit of normal.
23. Known to be positive to the human immunodeficiency virus (HIV)1 or HIV2 virus.
24. Known hypersensitivity to the excipients of SLV337 capsules (lactose monohydrate, sucrose, hydroxypropyl methylcellulose, sodium lauryl sulfate, sodium docusate, purified water, sodium starch glycolate and magnesium stearate).
25. Has taken one single dose of an investigational drug within 30 days or multiple doses of an investigational drug within 60 days prior to dosing.
26. Has an acute infection a