Clinical trial NCT00995345: Safety and Efficacy of Once-Daily KRP-104 in Type 2 Diabetics With Inadequate Glycemic Control on Metformin Alone
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes
Keywords: Type 2 Diabetes
Metformin
Lead sponsor: ActivX Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Kyorin Pharmaceutical Co.,Ltd
First posted: 2009-10-15
Enrollment: 403
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in HbA1c From Baseline (Week 0) to Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Change in Body Weight
timeFrame: 24 weeks
measure: Percentage of Patients Achieving HbA1c Less Than 7%
timeFrame: 24 weeks
measure: Percentage of Patients Requiring Rescue Therapy for Elevated Glucose
timeFrame: 24 weeks of treatment.
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Valley Village
country: United States
state: California
city: Honolulu
country: United States
state: Hawaii
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Delaware
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Beaver
country: United States
state: Pennsylvania
city: Jenkintown
country: United States
state: Pennsylvania
city: Greer
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sandy
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Ciudad Autonoma de Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Loma Hermos Buenos Aires
country: Argentina
city: Chrudim III
country: Czech Republic
city: Holesov
country: Czech Republic
city: Melnik
country: Czech Republic
city: Ostrava
country: Czech Republic
city: Praha 10
country: Czech Republic
city: Praha 8
country: Czech Republic
city: Guatemala City
country: Guatemala
city: Bialystok
country: Poland
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Arkhangel'sk
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Port Elizabeth
country: South Africa
state: Eastern Cape
city: Bloemfontein
country: South Africa
state: Free State
city: Johannesburg
country: South Africa
state: Gauteng
city: Soweto
country: South Africa
state: Gauteng
city: Durban
country: South Africa
state: Kwazula-Natal
city: Cape Town
country: South Africa
state: Western Cape
city: Paarl
country: South Africa
state: Western Cape
city: Somerset West
country: South Africa
state: Western Cape
Study officials:
affiliation: ActivX Biosciences, Inc.
name: Diane J Plotkin, PhD
role: STUDY_DIRECTOR
References:
citation: 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.