Safety and Efficacy of Once-Daily KRP-104 in Type 2 Diabetic Patients That Cannot Control Their Diabetes on Metformin Alone (Synergy 104)

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: July 17, 2012
Last verified: July 2012
  Purpose

The purpose of this study is to assess the safety and effectiveness of KRP-104 on diabetes 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: Every 4 weeks up to 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in insulin, HOMA-IR, and HOMA-β [ Time Frame: Every 4 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Change in body weight [ Time Frame: Every 4 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Change in HbA1c, FPG, insulin, HOMA-IR, HOMA-β, and body weight. [ Time Frame: Every 4 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Number and percentage of patients achieving HbA1c less than 7% [ Time Frame: Every 4 weeks up to 20 weeks. ] [ Designated as safety issue: No ]
  • Number and percentage of patients requiring rescue therapy for elevated glucose [ Time Frame: At the end of 24 weeks of treatment. ] [ Designated as safety issue: Yes ]

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
Tablet
Drug: KRP-104
Tablet
Experimental: Dose 2: KRP-104
Tablet
Drug: KRP-104
Tablet
Experimental: Dose 3: KRP-104
Tablet
Drug: KRP-104
Tablet
Experimental: Dose 4: KRP-104
Tablet
Drug: KRP-104
Tablet
Placebo Comparator: Placebo
Tablet
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
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
  More Information

No publications provided

Responsible Party: ActivX Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT00995345     History of Changes
Other Study ID Numbers: 0104-005
Study First Received: October 12, 2009
Last Updated: July 17, 2012
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
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 14, 2014