A Study of RO5095932 in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled study will assess the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of RO5095932 in patients with type 2 diabetes mellitus. Patients will be randomized to receive either RO5095932 subcutaneously once weekly or placebo for 4 weeks (part 1) or 6 weeks (part 2), in addition to their current stable doses of metformin.

Official Title
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A Multi-Center, Randomized, Double-Blind, Multiple Ascending Dose, Placebo-Controlled, Parallel Group, 2-Part Study to Investigate the Safety, Tolerability, PK, and PD of Once Weekly RO5095932 in Patients With Type 2 Diabetes Mellitus on a Stable Dose of Metformin

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: RO5095932
* Drug: RO5095932
* Drug: metformin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-65 years of age females who are either surgically sterile or post-menopausal type 2 diabetes treated with a stable dose of metformin BMI between 25-39kg/m2 HbA1c between 7 and 10% fasting plasma glucose between 7 and 13.3mmol/L Exclusion Criteria: history of clinically significant cardiovascular disease history of clinically significant hepatic or renal disease or impairment recent therapy with insulin, thiazolidinedione, glucagon-like peptide-1 analogues, amylin analogues and/or DPP-IV inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1active<br> | Drug: RO5095932<br>* cohorts receiving multiple ascending doses, sc once weekly for 4 weeks<br>Drug: metformin<br>* stable dose<br>|
| Placebo Comparator: 1placebo<br> | Drug: metformin<br>* stable dose<br>Drug: placebo<br>* sc once weekly for 4 weeks<br>|
| Experimental: 2active<br> | Drug: RO5095932<br>* dose titration to target dose, sc once weekly for 6 weeks<br>Drug: metformin<br>* stable dose<br>|
| Placebo Comparator: 2placebo<br> | Drug: metformin<br>* stable dose<br>Drug: placebo<br>* sc once weekly for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: AEs, laboratory parameters, ECG, body weight, vital signs |  | monitored throughout study, with weekly ECG and 2x weekly to 2-weekly laboratory assessments on study treatment and at intervals during follow-up | 
| Change in hemoglobin A1c (HbA1c) |  | from baseline to week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: blood concentration of RO5095932 after multiple dosing |  | multiple sampling weeks 1-4 or 1-6 respectively, and weekly during follow-up | 
| Change in metabolic parameters: glucose, insulin, C-peptide |  | assessed after 4 or 6 weeks on study treatment |