A Dose-Finding Study of RO4998452 in Patients With Diabetes Mellitus

Study Overview
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Brief Summary
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This 6 arm study will evaluate the efficacy, safety and pharmacokinetics of 5 doses of RO4998452 compared to placebo in patients with type 2 diabetes mellitus. Patients will be randomized to one of 6 groups to receive RO4998452 at doses of 2.5mg, 5mg, 10mg, 20mg or 40mg po daily, or placebo daily. Patients pre-treated with stable metformin will continue to take their usual dose of metformin throughout the study.The anticipated time on study treatment is <=3 months

Official Title
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A Multi-center, Double-blind, Randomized, Parallel Group, Placebo-controlled 12-week Study to Investigate Glycemic Parameters of Efficacy, Safety/ Tolerability and Pharmacokinetics of Five Dose Levels of RO4998452 in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: RO4998452
* Drug: RO4998452
* Drug: RO4998452
* Drug: RO4998452
* Drug: RO4998452


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-75 years of age; type 2 diabetes, diagnosed for >=3 months; either treated with diet, exercise and stable metformin, or with diet and exercise alone. Exclusion Criteria: type 1 diabetes mellitus; currently or within 2 months prior to screening treated with an oral or injectable anti-diabetic agent except stable doses of metformin; currently or within 6 months prior to screening treated with any PPARgamma agonist; uncontrolled hypertension; significant pre-diagnosed diabetic complications requiring treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. | Drug: Placebo<br>* po daily for 12 weeks<br>|
| Experimental: RO4998452 10mg<br>During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452. | Drug: RO4998452<br>* 10mg po daily for 12 weeks<br>|
| Experimental: RO4998452 2.5mg<br>During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452. | Drug: RO4998452<br>* 2.5mg po daily for 12 weeks<br>|
| Experimental: RO4998452 20mg<br>During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452. | Drug: RO4998452<br>* 20mg po daily for 12 weeks<br>|
| Experimental: RO4998452 40mg<br>During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452. | Drug: RO4998452<br>* 40mg po daily for 12 weeks<br>|
| Experimental: RO4998452 5mg<br>During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452. | Drug: RO4998452<br>* 5mg po daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in HbA1c |  | Baseline, Week 4, Week 8 and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (mmol/L) |  | Baseline and Week 12 | 
| Change From Baseline in Mean Daily Glucose Concentration (mmol/L) |  | Baseline and Week 12 | 
| Change From Baseline in Fructosamine Concentration (μmol/L) |  | Baseline and 12 weeks | 
| Change From Baseline in Meal Tolerance Test: 0-3h Mean Glucose Concentration (mmol/L) |  | Baseline and Week 12 | 
| Change From Baseline in Meal Tolerance Test: 0-3h Mean Insulin Concentration (mmol/L) |  | Baseline and Week 12 | 
| Change From Baseline in Meal Tolerance Test: 0-3h Urinary Glucose Excretion (mmol/L) |  | Baseline and Week 12 | 
| Change From Baseline in Body Weight (kg) |  | Baseline and Week 12 | 
| Percentage of Participants Treated to Target HbA1c < 7% |  | Baseline up to 12 weeks | 
| Percentage of Participants Treated to Target HbA1c < 6.5% |  | Baseline up to 12 weeks | 
| Percentage of Participants With at Least One Adverse Event |  | Baseline up to 12 weeks |