A Study to Investigate in Healthy Volunteers (Part 1) and in Patients With Type 2 Diabetes Mellitus (Part 2) the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of RO6799477

Recruitment & Eligibility

Inclusion Criteria

Part 1 Inclusion criteria:

Right-handed male volunteers
Aged 18-45 years, inclusive
Healthy participants, as determined by screening assessments and Principal Investigator's judgment
Healthy status is defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, serology and urinalysis
Body Mass Index (BMI) of 18-30 kg/m2 inclusive, with body weight in the range of 50-100 kg

Part 2 Inclusion Criteria:

Patients with type 2 diabetes according to WHO criteria diagnosed for at least 3 months prior to screening
Male or female patients, 40 to 65 years of age, inclusive
Type 2 diabetic patients who are either drug naive (diet & exercise alone) or on a stable dose of metformin for at least 3 months prior to screening or willing to safely stop sulfonylurea medications at least 2 weeks prior to first dose administration and until follow-up visit
BMI of 23-42 kg/m2, inclusive

Exclusion Criteria

Part 1 Exclusion criteria:

Any clinically relevant history or the presence of e.g. respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, psychiatric, etc. disease or diseases
Disorders of central nervous system, psychiatric disorders, behavioral disturbances (e.g. cerebrovascular events, depression, post-traumatic stress disorder [PTSD], anxiety, bipolar disorder, severe migraine, Parkinson's disease)
Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times per year
Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study

Part 2 Exclusion Criteria:

Type 1 diabetes
Acquired or secondary forms of diabetes such as those resulting from pancreatic surgery/injury, cystic fibrosis related diabetes
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 or already diagnosed by the diabetologist or general practitioner
Disorders of central nervous system, psychiatric disorders, behavioral disturbances
Clinically significant history or presence of bronchopulmonary, gastrointestinal, hematological, lymphatic, neurological, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, infectious, connective tissue or inflammatory diseases, and any type of cancer (with the exception of treated basal cell carcinoma of the skin) or other clinically significant disease
Use of anti-diabetic drugs other than metformin or sulfonylureas within 2 months prior to screening
Any condition or disease detected during the medical interview / physical examination that would render the patient unsuitable for the study, place the patient at undue risk or interfere with the ability of the patient to complete the study in the opinion of the investigator

Study & Design

Arm && Interventions

Group	Intervention	Description
Part 1: Healthy Volunteers	RO6799477	-
Part 1: Healthy Volunteers	Placebo	-
Part 2: Patients with T2D, Group A	Placebo	Low dose daily oral administration of RO6799477
Part 2: Patients with T2D, Group A	RO6799477	Low dose daily oral administration of RO6799477
Part 2: Patients with T2D, Group B	Placebo	High dose daily oral administration of RO6799477
Part 2: Patients with T2D, Group B	RO6799477	High dose daily oral administration of RO6799477

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (AEs)	Up to 9 weeks

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic parameters derived from plasma and urine concentrations of RO6799477, area under the concentration time curve (AUC), Cmax	Day 1 and Day 14
Fasting serum glucose	Up to 9 weeks
Fasting serum insulin (Part 2 only)	Up to 9 weeks

Recruitment & Eligibility