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

Type 2 Diabetes Clinical Trial

— Synergy104  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00995345
• Other study ID #: 0104-005
• Status: Completed
• Phase: Phase 2
• First received: October 12, 2009
• Last updated: June 23, 2014
• Start date: October 2009
• Est. completion date: January 2011

Study information

• Verified date: June 2014
• Source: ActivX Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardArgentina: Human Research Bioethics CommitteeArgentina: Ministry of HealthCzech Republic: Ethics CommitteeCzech Republic: State Institute for Drug ControlPoland: Ethics CommitteePoland: Ministry of HealthRussia: Ethics CommitteeRussia: Ministry of Health and Social Development of theSouth Africa: Medicines Control CouncilSouth Africa: Human Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 403
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• KRP-104
Tablet
• Placebo
Tablet

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
ActivX Biosciences, Inc.	Kyorin Pharmaceutical Co.,Ltd

Countries where clinical trial is conducted

United States,  Argentina,  Czech Republic,  Guatemala,  Poland,  Russian Federation,  South Africa, 

References & Publications (1)

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,

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change in Body Weight	Mean Change in Body Weight (kg) from Baseline to Week 24 with LOCF- ITT	24 weeks	Yes
Secondary	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	No
Secondary	Percentage of Patients Requiring Rescue Therapy for Elevated Glucose	Percentage of Subjects Requiring Rescue Therapy - Intent-to-Treat Population	24 weeks of treatment.	Yes