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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: KRP-104 QD Drug: Placebo Drug: Metformin; Drug: KRP-104 BID Drug: Placebo Drug: Metformin; Drug: Placebo Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 213
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 to 70 years, inclusive;
2. Males and females of non-childbearing potential;
3. Diagnosis of type 2 diabetes mellitus according; and
4. On a stable dose of metformin monotherapy at randomization (can be on other oral therapies or naive at study entry

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
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 [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;
5. Uncontrolled high blood pressure;
6. History or evidence of cardiovascular or pulmonary disease
7. Must meet other laboratory and Medical History clinical criteria. Please contact recruitment center for referrals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo Drug: Metformin; Two tablets 15 to 30 minutes before each meal, morning and evening.
Experimental: KRP-104 120 mg QD	Drug: KRP-104 QD Drug: Placebo Drug: Metformin; 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
Experimental: KRP-104 60 mg BID	Drug: KRP-104 BID Drug: Placebo Drug: Metformin; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: ActivX Biosciences, Inc.
• Collaborators: Kyorin Pharmaceutical Co.,Ltd
• Investigators: Study Chair: David Orloff, Medpace, Inc.; Study Chair: Tufail Syed, Medpace India

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: September 3, 2007
• First Submitted That Met QC Criteria: September 4, 2007
• First Posted (Estimate): September 5, 2007

Study Record Updates

• Last Update Posted (Estimate): August 22, 2013
• Last Update Submitted That Met QC Criteria: August 14, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 0104-003