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

This study has been completed.
Sponsor:
Collaborator:
Kyorin Pharmaceutical Co.,Ltd
Information provided by (Responsible Party):
ActivX Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT00995345
First received: October 12, 2009
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Drug: KRP-104
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by ActivX Biosciences, Inc.:

Primary Outcome Measures:
  • Change in HbA1c From Baseline (Week 0) to Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Mean Change in HbA1c (%) from Baseline to Week 24 with LOCF, ITT population LS mean (SE)


Secondary Outcome Measures:
  • Change in Body Weight [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Mean Change in Body Weight (kg) from Baseline to Week 24 with LOCF- ITT

  • Percentage of Patients Achieving HbA1c Less Than 7% [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks of treatment. ] [ Designated as safety issue: Yes ]
    Percentage of Subjects Requiring Rescue Therapy - Intent-to-Treat Population


Enrollment: 403
Study Start Date: October 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00995345

  Show 46 Study Locations
Sponsors and Collaborators
ActivX Biosciences, Inc.
Kyorin Pharmaceutical Co.,Ltd
Investigators
Study Director: Diane J Plotkin, PhD ActivX Biosciences, Inc.
  More Information

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.

Responsible Party: ActivX Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT00995345     History of Changes
Other Study ID Numbers: 0104-005
Study First Received: October 12, 2009
Results First Received: August 14, 2013
Last Updated: June 23, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Argentina: Human Research Bioethics Committee
Argentina: Ministry of Health
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Poland: Ethics Committee
Poland: Ministry of Health
Russia: Ethics Committee
Russia: Ministry of Health and Social Development of the
South Africa: Medicines Control Council
South Africa: Human Research Ethics Committee

Keywords provided by ActivX Biosciences, Inc.:
Type 2 Diabetes
Metformin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014