A Safety, Pharmacokinetics and Pharmacodynamics Study of RO6811135 in Patients With Type 2 Diabetes Mellitus

• Pharmacokinetics: Area under the concentration-time curve (AUC) [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
• Pharmacodynamics of RO681135: Blood analysis [ Time Frame: 14 days ] [ Designated as safety issue: No ]

This randomized, double-blind, placebo-controlled, multiple ascending dose study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of RO6811135 in patients with type 2 diabetes mellitus. Patients will be randomized to receive either RO6811135 or placebo daily for 2 weeks, with a follow-up examination 2 to 3 weeks after the last dose of study drug.

• Drug: Placebo
  Matching placebo, multiple doses
• Drug: RO6811135
  multiple ascending doses

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: RO6811135
  Intervention: Drug: RO6811135

Inclusion Criteria:

• Adult patients, 18 to 65 years of age, inclusive
• Type 2 diabetes mellitus according to WHO criteria diagnosed for at least 3 months prior to screening
• On stable dose of metformin for at least 2 months prior to screening
• Fasting plasma glucose during the screening period </= 240 mg/dL
• Hemoglobin A1c (HbA1c) levels at screening >/= 6.5% and </= 10.5%
• Evidence of insulin secretory capacity at screening
• Body mass index (BMI) 27 to 42 kg/m2, inclusive
• Females of child-bearing potential and males with female partners of child-bearing potential must agree to use effective contraception as defined by protocol

Exclusion Criteria:

• Type 1 diabetes
• Acquired or secondary forms of diabetes such as those resulting from pancreatic surgery/injury, cystic fibrosis related diabetes
• History of acute metabolic complications such as diabetic ketoacidosis or state of hyperosmolar hyperglycemia
• Evidence or history of clinically significant diabetic complications such as clinically severe diabetic peripheral neuropathy, clinically significant nephropathy as judged by the investigator, or pre-proliferative/proliferative diabetic retinopathy as judged by the investigator
• History of severe symptomatic hypoglycemia (requiring assistances of a third party) within 6 months prior to screening
• History or presence of clinically significant concomitant disease or disorder
• Hemoglobin level below the lower limit of reference range at screening
• Pregnant or lactating women
• History of anaphylaxis or severe systemic hypersensitivity or allergic reactions