Safety and Efficacy of Once-Daily KRP-104 in Type 2 Diabetics With Inadequate Glycemic Control on Metformin Alone
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2
Intervention: KRP-104; Placebo
Intervention description: Tablet; Tablet
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 403.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Type 2 Diabetes; Metformin

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