A Safety Study of ARRY-403 in Patients With Type 2 Diabetes

• Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests, vital signs and electrocardiograms. [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
• Characterize the pharmacokinetics (PK) of the study drug and metabolites in terms of plasma concentrations. [ Time Frame: Day 1, Day 2 ] [ Designated as safety issue: No ]

• Adverse events, physical examinations, clinical laboratories, ECGs and vital sign assessments [ Time Frame: Screening, Day 1, Day 2, Day 8 ] [ Designated as safety issue: Yes ]
• Exposure to the investigational drug and metabolites [ Time Frame: Day 1, Day 2 ] [ Designated as safety issue: No ]

• Characterize the pharmacodynamic (PD) activity of the study drug on biomarkers. [ Time Frame: Day 1, Day 2 ] [ Designated as safety issue: No ]
• Assess the ability of the study drug to improve glucose tolerance as determined by blood glucose monitoring during a standardized meal challenge. [ Time Frame: Day 1, Day 2 ] [ Designated as safety issue: No ]
• Assess the excretion of the study drug and metabolites in urine following dosing. [ Time Frame: Day 1, Day 2 ] [ Designated as safety issue: No ]

• Characterization of the pharmacodynamic activity of the investigational drug on biomarkers [ Time Frame: Day 1, Day 2 ] [ Designated as safety issue: No ]
• Assessment of the ability of investigational drug to improve glucose tolerance [ Time Frame: Day 1, Day 2 ] [ Designated as safety issue: No ]
• Assessment of the excretion from the body of the investigational drug and metabolites [ Time Frame: Day 1, Day 2 ] [ Designated as safety issue: No ]

This is a Phase 1 study, involving a 1-day dosing period, designed to test the safety of investigational study drug ARRY-403 in patients with Type 2 diabetes. Approximately 36 patients from the US will be enrolled in this study.

• Drug: ARRY-403, glucokinase activator; oral
  single dose, escalating
• Drug: Placebo; oral
  matching placebo

• Experimental: ARRY-403
  Intervention: Drug: ARRY-403, glucokinase activator; oral
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo; oral

Key Inclusion Criteria:

• Male or female with willingness and ability to use protocol-specified methods of contraception, except females of nonchildbearing potential.
• Diagnosis of Type 2 diabetes less than 5 years prior to study start.
• HbA1c ≥ 6.5% and ≤ 10%.
• BMI ≥ 25 and ≤ 40.0 kg/m2.
• Additional criteria exist.

Key Exclusion Criteria:

• Recent history (i.e., less than 6 months) or concomitant/ongoing clinically significant hematologic, renal, pulmonary, gastrointestinal, hepatic, psychiatric, neurologic, dermatologic, or allergic disease (including drug allergies that are clinically significant and not remote, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Significant cardiac disease, myocardial infarction within 6 months of study start, unstable angina, congestive heart failure, known arrhythmias of ventricular etiology, unexplained syncope or syncope/seizures related to arrhythmia.
• History of gastric surgery, vagotomy, bowel resection, or any surgical procedure that might interfere with gastrointestinal motility, pH, or absorption.
• Active infectious diseases including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Past history and inactive hepatitis B and C, as confirmed by serological testing, are allowed.
• A positive test for drugs or alcohol.
• Women who are pregnant or breastfeeding.
• Donation or loss of ≥ 550 mL of blood (including plasmapheresis) or receipt of a transfusion of any blood product within 8 weeks prior to first dose of study drug.
• Additional criteria exist.