Safety and Efficacy of Once-Daily KRP-104 in Type 2 Diabetics With Inadequate Glycemic Control on Metformin Alone (Synergy104)

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.

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 403
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aires, Argentina
  • Cordoba, Argentina
  • Loma Hermos Buenos Aires, Argentina
• Czech Republic
  • Chrudim III, Czech Republic
  • Holesov, Czech Republic
  • Melnik, Czech Republic
  • Ostrava, Czech Republic
  • Praha 10, Czech Republic
  • Praha 8, Czech Republic
• Guatemala
  • Guatemala City, Guatemala
• Poland
  • Bialystok, Poland
  • Gdansk, Poland
  • Krakow, Poland
  • Lodz, Poland
  • Warszawa, Poland
  • Wroclaw, Poland
• Russian Federation
  • Arkhangel'sk, Russian Federation
  • Kemerovo, Russian Federation
  • Moscow, Russian Federation
  • Novosibirsk, Russian Federation
  • St. Petersburg, Russian Federation
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa
  • Free State
    • Bloemfontein, Free State, South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa
    • Soweto, Gauteng, South Africa
  • Kwazula-Natal
    • Durban, Kwazula-Natal, South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa
    • Paarl, Western Cape, South Africa
    • Somerset West, Western Cape, South Africa
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arizona
    • Phoenix, Arizona, United States
  • California
    • Los Angeles, California, United States
    • Valley Village, California, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • North Carolina
    • Winston-Salem, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Delaware, Ohio, United States
    • Marion, Ohio, United States
  • Pennsylvania
    • Beaver, Pennsylvania, United States
    • Jenkintown, Pennsylvania, United States
  • South Carolina
    • Greer, South Carolina, United States
  • Texas
    • Austin, Texas, United States
    • Houston, Texas, United States
    • San Antonio, Texas, United States
  • Utah
    • Sandy, Utah, United States
    • West Jordan, Utah, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: ActivX Biosciences, Inc.
• Collaborators: Kyorin Pharmaceutical Co.,Ltd
• Investigators: Study Director: Diane J Plotkin, PhD, ActivX Biosciences, Inc.

Publications and helpful links

General Publications

• Plotkin DJ, Lewin A, Logan D, Kato T, Kozarich J, Wei X, Vest J, Orloff D. KRP-104, A Uniquely Prandial-Targeted DPP-4 Inhibitor. Abstract and Poster # 822, Presented at: European Association for the Study of Diabetes 38th Annual Meeting, Berlin Germany, October 1-5, 2012.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ACTUAL): January 1, 2011
• Study Completion (ACTUAL): January 1, 2011

Study Registration Dates

• First Submitted: October 12, 2009
• First Submitted That Met QC Criteria: October 14, 2009
• First Posted (ESTIMATE): October 15, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 26, 2014
• Last Update Submitted That Met QC Criteria: June 23, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Metformin; Type 2 Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 0104-005