12-week study of ds-8500a in subjects with type 2 diabetes mellitus on metformin

Conditions: Type 2 Diabetes Mellitus

Summary: the hypothesis of this phase 2, 12-week study, is that ds-8500a will improve glycemic control relative to placebo, based on changes in hba1c, with acceptable safety and tolerability, in patients with type 2 diabetes mellitus (t2dm) who are treated with metformin.


Eligibility criteria:
inclusion criteria: * able to provide written informed consent and adhere to the study visit schedule and treatment * diagnosed with type 2 diabetes mellitus as defined in the american diabetes association standards of medical care in diabetes 2015 * male or female ≥ 18 and ≤ 70 years of age * screening fasting c-peptide \> 0.5 ng/ml * women of child bearing potential (wocbp) must be willing to use double-barrier contraception for the entire study * wocbp must have a negative pregnancy test (human chorionic gonadotropin, beta subunit \[βhcg\]) before entering the lead-in period * body mass index ≥ 25 kg/m2 and ≤ 45 kg/m2 at the screening visit * on stable (≥ 8 weeks) metformin monotherapy ≥ 1000 mg/day * screening hba1c ≥ 7.0% and ≤ 10% * taking ≥ 80% and ≤ 120% of both dispensed ds-8500a placebo tablets and sitagliptin placebo capsules during the lead-in period exclusion criteria: * history of type 1 diabetes and/or history of ketoacidosis * history of insulin use for \> 2 weeks within 2 months prior to the screening visit * two or more readings of fasting self-monitoring of blood glucose (smbg) \> 240 mg/dl or worsening symptoms of hyperglycemia with one smbg level of \> 240 mg/dl during the second week of lead-in period, confirmed by laboratory measurement * screening hemoglobin \<12 g/dl for males and \<11 g/dl for females * blood donation within 2 months prior to the screening visit or plans to donate blood or blood products during the study * subjects after bariatric surgery or any gastric bypass * screening thyroid stimulating hormone (tsh) levels not within normal range (based on reference laboratory values ) * screening alanine aminotransferase (alt) or aspartate aminotransferase (ast) \> 2.0 x upper limit of normal (uln), and/or total bilirubin \> 1.5 x uln. if a subject has total bilirubin \> 1.5 uln, unconjugated and conjugated bilirubin fractions should be analyzed and only subjects documented to have gilbert's syndrome may be enrolled * screening serum creatinine ≥ 1.5 mg/dl for males and ≥ 1.4 mg/dl for females, or creatinine clearance (crcl) \< 50 ml/min for both males and females * screening creatine kinase (ck) \> 3.0 × uln * history of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, peripheral arterial event or any revascularization procedure during the 6 months prior to the screening visit or planned vascular procedures or surgery during study period * history of congestive heart failure (chf) * exclusionary concomitant medications: a. eight weeks prior to screening and throughout the duration of the study: * any diabetes medication other than metformin; any prescription or over the counter medication for weight-loss. * systemic corticosteroids (including nasal and inhaled), with the exception of use of topical and ophthalmic corticosteroids. * rosuvastatin \> 20 mg daily. b. during treatment periods, additional medications will be prohibited based on potential drug-drug interaction (ddi) (see section 5.6) * subjects with anticipated interruption in metformin or study drug use during the course of the clinical trial (e.g., due to an imaging procedure involving iodinated contrast media) * subjects in whom treatment with sitagliptin 100 mg is contraindicated ( e.g., known hypersensitivity or intolerance to sitagliptin) or may not be medically advisable (e.g., history of pancreatitis) * abuse of or dependence on prescription medications, illicit drugs, or alcohol within the last 1 year * any history of a malignancy other than basal cell carcinoma within the past 5 years * pregnancy or breast-feeding, or intent to become pregnant during the study period * known (or evidence of) infection with human immunodeficiency virus * any condition, laboratory abnormality, or concomitant therapy which, in the opinion of the investigator, might pose a risk to the subject or make participation not in the subject's best interest * subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents * a direct or familial relationship with the sponsor, investigator, or site personnel affiliated with the study

Keywords: type 2 diabetes mellitus interventional double blind phase 2