A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of KRP-104 in Patients With Type 2 Diabetes Inadequately Controlled on Metformin Alone

Study Overview
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Brief Summary
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To assess the safety and efficacy of chronic therapy with KRP-104, a novel DPP-IV inhibitor, in patients with Type 2 Diabetes on stable metformin therapy. In addition, an estimate of how much of the HbA1c response is attributable to nocturnal coverage will be explored.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of KRP-104 in Patients With Type 2 Diabetes Inadequately Controlled on Metformin Alone

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: KRP-104 QD Drug: Placebo Drug: Metformin
* Drug: Placebo Drug: Metformin
* Drug: KRP-104 BID Drug: Placebo Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 70 years, inclusive; Males and females of non-childbearing potential; Diagnosis of type 2 diabetes mellitus according; and On a stable dose of metformin monotherapy at randomization (can be on other oral therapies or naive at study entry Exclusion Criteria: History of type 1 diabetes mellitus or history of diabetic ketoacidosis or persistent hypoglycemia; History or presence of alcoholism or drug abuse Typical consumption of ≥10 drinks of alcohol weekly; Presence of any of the following conditions: Significant renal impairment (glomerular filtration rate <60 mL/min [to be calculated by the central laboratory]); Diabetic retinopathy; Diabetic gastroparesis; Active liver disease (other than asymptomatic nonalcoholic fatty liver disease), cirrhosis, or symptomatic gallbladder disease; Uncontrolled high blood pressure; History or evidence of cardiovascular or pulmonary disease Must meet other laboratory and Medical History clinical criteria. Please contact recruitment center for referrals

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KRP-104 120 mg QD<br> | Drug: KRP-104 QD Drug: Placebo Drug: Metformin<br>* KRP-104 120 mg: KRP-104 two 50 mg tablets and two 10 mg tablets 15 to 30 minutes before morning meal and 2 placebo tablets 15 to 30 minutes before evening meal<br>|
| Experimental: KRP-104 60 mg BID<br> | Drug: KRP-104 BID Drug: Placebo Drug: Metformin<br>* KRP-104 60 mg: KRP-104 one 50 mg tablet plus one 10 mg tablet 15 to 30 minutes before each meal, morning and evening.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo Drug: Metformin<br>* Two tablets 15 to 30 minutes before each meal, morning and evening.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of this trial is to demonstrate the hemoglobin A1c (HbA1c)-lowering effects of KRP-104 in patients with type 2 diabetes inadequately controlled on metformin alone. |  | 12-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the fasting plasma glucose (FPG)-lowering effect of KRP-104 in patients with type 2 diabetes inadequately controlled on metformin alone; |  | 12-weeks | 
| To compare effects of once daily (QD) dosing versus twice daily (BID) dosing of KRP-104 on HbA1c and FPG |  | 12 weeks | 
| To assess the effects of KRP-104 on post-prandial glucose dynamics and insulin sensitivity (homeostasis model index [HOMA-β]) in the setting of a Meal Tolerance Test(MTT) | Changes from pre-prandial to 2-hour post-prandial glucose, active GLP-1, insulin summarized by treatment group from Week 0 to Week 5 and Week 12. Percent change in 2-hour post-prandial glucose summarized by treatment group from Week 0 to Week 5 and Week 12. | 12 weeks | 
| To assess the safety and tolerability of KRP-104; |  | Daily for 12 weeks to 2 weeks post-treatment |