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

NCT ID: NCT00995345

Last Updated: 2014-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 403 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2011-01-31

Brief 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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dose 4: KRP-104 20/120mg

Tablet, once-daily for 24 weeks (dose switch from 20 to 120 mg at week 12)

Group Type: EXPERIMENTAL

KRP-104

Intervention Type: DRUG

Tablet

Placebo

Tablet, once-daily for 24 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablet

Dose 1: KRP-104 40 mg

Tablet, once-daily for 24 weeks

Group Type: EXPERIMENTAL

KRP-104

Intervention Type: DRUG

Tablet

Dose 2: KRP-104 80 mg

Tablet, once-daily for 24 weeks

Group Type: EXPERIMENTAL

KRP-104

Intervention Type: DRUG

Tablet

Dose 3: KRP-104 100 mg

Tablet, once-daily for 24 weeks

Group Type: EXPERIMENTAL

KRP-104

Intervention Type: DRUG

Tablet

Interventions

KRP-104

Tablet

Intervention Type: DRUG

Placebo

Tablet

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyorin Pharmaceutical Co.,Ltd

INDUSTRY

Sponsor Role: collaborator

ActivX Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Diane J Plotkin, PhD

Role: STUDY_DIRECTOR

ActivX Biosciences, Inc.

Locations

Birmingham, Alabama, United States

Phoenix, Arizona, United States

Los Angeles, California, United States

Valley Village, California, United States

Honolulu, Hawaii, United States

Winston-Salem, North Carolina, United States

Cincinnati, Ohio, United States

Delaware, Ohio, United States

Marion, Ohio, United States

Beaver, Pennsylvania, United States

Jenkintown, Pennsylvania, United States

Greer, South Carolina, United States

Austin, Texas, United States

Houston, Texas, United States

San Antonio, Texas, United States

Sandy City, Utah, United States

West Jordan, Utah, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Loma Hermos Buenos Aires, , Argentina

Chrudim III, , Czechia

Holešov, , Czechia

Mělník, , Czechia

Ostrava, , Czechia

Prague, , Czechia

Guatemala City, , Guatemala

Bialystok, , Poland

Gdansk, , Poland

Krakow, , Poland

Lodz, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Arkhangelsk, , Russia

Kemerovo, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Saint Petersburg, , Russia

Port Elizabeth, Eastern Cape, South Africa

Bloemfontein, Free State, South Africa

Johannesburg, Gauteng, South Africa

Soweto, Gauteng, South Africa

Durban, Kwazula-Natal, South Africa

Cape Town, Western Cape, South Africa

Paarl, Western Cape, South Africa

Somerset West, Western Cape, South Africa

Countries

United States; Argentina; Czechia; Guatemala; Poland; Russia; South Africa

References

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.

Reference Type: RESULT

Other Identifiers

0104-005

Identifier Type: -

Identifier Source: org_study_id