A 24-Week, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Once-Daily KRP-104 in Patients with Type 2 Diabetes with Inadequate Glycemic Control on Metformin Alone - Synergy 104

• Conditions: Type 2 Diabetes with Inadequate Glycemic Control on Metformin Alone; MedDRA version: 12.0Level: LLTClassification code 10067585Term: Type 2 diabetes mellitus

• Registration Number: EUCTR2009-015071-27-CZ
• Lead Sponsor: ActivX Biosciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-06
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Signed written informed consent;
2. Males and females 18 to 75 years of age, inclusive;
3. Females of childbearing potential must agree to use 2 adequate forms of barrier method contraception (eg, latex condom AND intrauterine device or a diaphragm) to avoid pregnancy while in the study;
4. On a stable dose (=10 weeks at the same dose) of metformin monotherapy
(=1500 mg/day or maximum tolerated dose), have an HbA1c =7.0% and =10.5%;
or
On metformin (=1500 mg/day) and 1 other antidiabetic agent (excluding
TZD, insulin, or incretin therapies [DPP-4 inhibitors and GLP-1 analogues])
and have an HbA1c =6.8% and =10.0%;
or
Not on antidiabetic therapy (for at least 3 months prior to Visit 1) or have not been on a stable dose of metformin monotherapy for 10 weeks and have an HbA1c =8.0% and =11.0%.
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. History of type 1 diabetes mellitus or history of diabetic ketoacidosis or persistent hypoglycemia;
2. History or presence of alcoholism or drug abuse within the 2 years prior to dosing;
3. Typical consumption of =10 drinks of alcohol weekly;
4. Presence of any of the following conditions:
• Significant renal impairment (glomerular filtration rate <60 mL/min);
• Diabetic gastroparesis;
• Active liver disease (other than asymptomatic nonalcoholic fatty liver disease), cirrhosis, or symptomatic gallbladder disease;
5. Fasting plasma glucose/blood glucose >240 mg/dL (13.3 mmol/L) at Visit 3 (Week -2) (1 laboratory retest permitted);
6. Body mass index =20 kg/m2 and =48 kg/m2;
7. Systolic blood pressure <100 mmHg or >160 mmHg and diastolic blood pressure <50 mmHg or >100 mmHg at Visit 3 (Note: medication to control blood pressure is allowed and should be optimized and stabilized prior to Visit 3);
8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN) (1 laboratory retest permitted);
9. Creatine phosphokinase (CPK) >2 × the ULN (if not explained by muscular
trauma or exercise) (1 laboratory retest permitted);
10. Serum creatinine <1.6 mg/dL (141.4 µmol/L);
11. Fasting triglycerides (TG) >600 mg/dL (6.78 mmol/L) at Visit 3 (Week -2) (Note: diet/exercise and lipid-lowering medication to control elevated TG is allowed; medications should be optimized and stabilized prior to Visit 3);
12. Treatment with pioglitazone or rosiglitazone within the previous 10 weeks (Visit 1); treatment with incretin therapy (DPP-4 inhibitors or GLP-1 analogues) within the previous 4 weeks (Visit 1);
13. Treatment with any type of insulin (ie, injected or inhaled) within the previous 3 months;
14. Thyroid hormone therapy that has not been stable for at least 3 months;
15. History or evidence of clinically significant cardiovascular, ECG abnormality, pulmonary, hepatic, renal, hematologic, gastrointestinal (including clinically significant malabsorption), endocrine (other than type 2 diabetes mellitus), immunologic, dermatologic, neurologic (including progressive neuromuscular disorders [eg, multiple sclerosis]), psychiatric, oncologic, or allergic (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) disease that would interfere with the conduct of the study or interpretation of the data.
Note: Significant cardiovascular disease includes but is not limited to any of the following within the previous 6 months: acute coronary syndrome such as myocardial infarction or unstable angina, coronary artery interventions such as percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery, congestive heart failure, stroke or peripheral vascular disease such as claudication or non-healing ischemic ulcer;
16. Requires treatment with medications with a narrow therapeutic range
(eg, digoxin or other cardiac glucosides, warfarin, warfarin-like (anticoagulants, phenytoin, anti-arrhythmic agents);
17. Requires chronic or repeated treatment with systemic corticosteroids (>14 days) or immunosuppressive/immunomodulating agents (eg, cyclosporine, Enbrel, methotrexate, rituximab);
18. Currently treated with weight-loss medications or had weight loss surgery
(eg, gastric bypass);
19. Known hypersensitivity or idiosyncratic reaction to DPP-4 inhibitors or to compounds structurally related to KRP-104;
20. Participation in another clinical trial within 30 days

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified