Safety and Efficacy of Once-Daily KRP-104 in Type 2 Diabetics With Inadequate Glycemic Control on Metformin Alone

Phase 2

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: KRP-104; Drug: Placebo

• Registration Number: NCT00995345
• Lead Sponsor: ActivX Biosciences, Inc.

Brief Summary

The purpose of this study is to assess the safety and effectiveness of KRP-104 on glycemic control in patients with type 2 diabetes inadequately controlled on metformin alone.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-10
• Study First Submitted: 2009-10-12
• Study First Submitted QC: 2009-10-14
• Study First Posted: 2009-10-15
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Results First Submitted: 2013-08-14
• Status Verified: 2014-06
• Results First Submitted QC: 2014-06-23
• Last Update Submitted: 2014-06-23
• Results First Posted: 2014-06-26
• Last Update Posted: 2014-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 403

Inclusion Criteria

Patients meeting the following criteria at the screening visit (Visit 1) will be eligible to participate in the trial:

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 (Greater than or equal to 10 weeks at the same dose) of metformin monotherapy (Less than or equal to 1500 mg/day or maximum tolerated dose), have an HbA1c greater than or equal to 7.0% and less than or equal to 10.5%; or

   • On metformin (less than or equal to 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 greater than or equal to 6.8% and less than or equal to 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 greater than or equal to 8.0% and less than or equal to 11.0%.

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 greater than or equal to 10 drinks of alcohol weekly;

4. Presence of any of the following conditions:

   • Significant renal impairment (glomerular filtration rate less than 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 greater than 240 mg/dL (13.3 mmol/L) at Visit 3 (Week -2) (1 laboratory retest permitted);

6. Body mass index less than or equal to 20 kg/m2 and greater than or equal to 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 X the upper limit of normal (ULN) (1 laboratory retest permitted);

9. Creatine phosphokinase (CPK) greater than 2 X the ULN (if not explained by muscular trauma or exercise) (1 laboratory retest permitted);

10. Serum creatinine >1.5 mg/dL for males (132.6 μmol/L) and 1.4 mg/dL for females (123.8 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. Must meet other laboratory and Medical History clinical criteria. Please contact recruitment center for referrals

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose 3: KRP-104 100 mg	KRP-104	Tablet, once-daily for 24 weeks
Dose 4: KRP-104 20/120mg	KRP-104	Tablet, once-daily for 24 weeks (dose switch from 20 to 120 mg at week 12)
Dose 1: KRP-104 40 mg	KRP-104	Tablet, once-daily for 24 weeks
Placebo	Placebo	Tablet, once-daily for 24 weeks
Dose 2: KRP-104 80 mg	KRP-104	Tablet, once-daily for 24 weeks

Primary Outcome Measures

Name	Time	Method
Change in HbA1c From Baseline (Week 0) to Week 24	Week 24	Mean Change in HbA1c (%) from Baseline to Week 24 with LOCF, ITT population LS mean (SE)

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients Achieving HbA1c Less Than 7%	24 weeks	Subjects Achieving Target of Hemoglobin A1c \<7.0% at Week 24 with LOCF - Intent-to-Treat Population
Percentage of Patients Requiring Rescue Therapy for Elevated Glucose	24 weeks of treatment.	Percentage of Subjects Requiring Rescue Therapy - Intent-to-Treat Population
Change in Body Weight	24 weeks	Mean Change in Body Weight (kg) from Baseline to Week 24 with LOCF- ITT