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

Study Overview
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Brief Summary
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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.

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

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: KRP-104
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients meeting the following criteria at the screening visit (Visit 1) will be eligible to participate in the trial: Signed written informed consent; Males and females 18 to 75 years of age, inclusive; 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; 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: History of type 1 diabetes mellitus or history of diabetic ketoacidosis or persistent hypoglycemia; History or presence of alcoholism or drug abuse within the 2 years prior to dosing; Typical consumption of greater than or equal to 10 drinks of alcohol weekly; 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; Fasting plasma glucose/blood glucose greater than 240 mg/dL (13.3 mmol/L) at Visit 3 (Week -2) (1 laboratory retest permitted); Body mass index less than or equal to 20 kg/m2 and greater than or equal to 48 kg/m2; 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); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 X the upper limit of normal (ULN) (1 laboratory retest permitted); Creatine phosphokinase (CPK) greater than 2 X the ULN (if not explained by muscular trauma or exercise) (1 laboratory retest permitted); Serum creatinine >1.5 mg/dL for males (132.6 μmol/L) and 1.4 mg/dL for females (123.8 μmol/L); 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); 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); Treatment with any type of insulin (ie, injected or inhaled) within the previous 3 months; 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: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1: KRP-104 40 mg<br>Tablet, once-daily for 24 weeks | Drug: KRP-104<br>* Tablet<br>|
| Experimental: Dose 2: KRP-104 80 mg<br>Tablet, once-daily for 24 weeks | Drug: KRP-104<br>* Tablet<br>|
| Experimental: Dose 3: KRP-104 100 mg<br>Tablet, once-daily for 24 weeks | Drug: KRP-104<br>* Tablet<br>|
| Experimental: Dose 4: KRP-104 20/120mg<br>Tablet, once-daily for 24 weeks (dose switch from 20 to 120 mg at week 12) | Drug: KRP-104<br>* Tablet<br>|
| Placebo Comparator: Placebo<br>Tablet, once-daily for 24 weeks | Drug: Placebo<br>* Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline (Week 0) to Week 24 | Mean Change in HbA1c (%) from Baseline to Week 24 with LOCF, ITT population LS mean (SE) | Week 24 | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes, Metformin