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

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

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Drug: Placebo; Drug: RO4998452; Drug: RO4998452; Drug: RO4998452; Drug: RO4998452; Drug: RO4998452

• Study Type: Interventional
• Enrollment (Actual): 394
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
  • St. Leonards, Australia, 2065
• Brazil
  • Fortaleza, Brazil, 60120-021
  • Goiania, Brazil, 74043011
  • Sao Paulo, Brazil, 01244-030
  • Sao Paulo, Brazil, 04022-001
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L8
  • Ontario
    • London, Ontario, Canada, NGA 4V2
    • Toronto, Ontario, Canada, M9W 4L6
    • Toronto, Ontario, Canada, M4G 3E8
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
• Germany
  • Berlin, Germany, 10115
  • Falkensee, Germany, 14612
  • Luebeck, Germany, 23562
  • Mainz, Germany, 55116
  • Neuss, Germany, 41460
• Hong Kong
  • Hong Kong, Hong Kong
  • Hong Kong, Hong Kong, 852
• Japan
  • Fukuoka, Japan, 812-0025
  • Ibaraki, Japan, 311-0113
  • Kanagawa, Japan, 232-0064
  • Osaka, Japan, 530-0001
  • Saitama, Japan, 343-0827
  • Saitama, Japan, 362-0021
  • Tokyo, Japan, 160-0017
  • Tokyo, Japan, 192-0071
• Latvia
  • Jelgava, Latvia, LV-3001
  • Riga, Latvia, 1002
  • Talsi, Latvia, 3200
  • Valmiera, Latvia, 4201
• Mexico
  • Chihuahua, Mexico, 31238
  • Guadalajara, Mexico, 44650
  • Guadalajara, Mexico, 44600
  • Mexico City, Mexico, 11650
• Romania
  • Alba-iulia, Romania, 51077
  • Brasov, Romania, 500365
  • Bucharest, Romania
  • Bucharest, Romania, 020475
  • Bucharest, Romania, 020045
  • Bucharest, Romania, 020725
  • Targu-mures, Romania, 540004
• Russian Federation
  • Moscow, Russian Federation, 129110
  • Moscow, Russian Federation, 117049
  • Moscow, Russian Federation, 119121
  • Nizhny Novgorod, Russian Federation, 603126
  • Novosibirsk, Russian Federation, 630047
  • S.petersburg, Russian Federation, 194017
  • Saratov, Russian Federation, 410038
  • St Petersburg, Russian Federation, 197198
  • St Petersburg, Russian Federation, 197089
  • St Petersburg, Russian Federation, 195257
  • St. Petersburg, Russian Federation, 191124
  • Yaroslavl, Russian Federation, 150062
• Spain
  • Alzira, Spain, 46600
  • Lerida, Spain, 25198
  • Sevilla, Spain, 41013
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85015
  • California
    • Los Angeles, California, United States, 90057
    • Palm Springs, California, United States, 92262
  • Florida
    • Bradenton, Florida, United States, 34208
    • Jacksonville, Florida, United States, 32216
  • Georgia
    • Atlanta, Georgia, United States, 30342
  • Idaho
    • Hayden Lake, Idaho, United States, 83835
  • New York
    • Rochester, New York, United States, 14609
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
  • Texas
    • Midland, Texas, United States, 79707
  • Virginia
    • Richmond, Virginia, United States, 23294

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; po daily for 12 weeks
Experimental: RO4998452 10mg; 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; 2.5mg po daily for 12 weeks; Drug: RO4998452; 5mg po daily for 12 weeks; Drug: RO4998452; 10mg po daily for 12 weeks; Drug: RO4998452; 20mg po daily for 12 weeks; Drug: RO4998452; 40mg po daily for 12 weeks
Experimental: RO4998452 2.5mg; 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; 2.5mg po daily for 12 weeks; Drug: RO4998452; 5mg po daily for 12 weeks; Drug: RO4998452; 10mg po daily for 12 weeks; Drug: RO4998452; 20mg po daily for 12 weeks; Drug: RO4998452; 40mg po daily for 12 weeks
Experimental: RO4998452 20mg; 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; 2.5mg po daily for 12 weeks; Drug: RO4998452; 5mg po daily for 12 weeks; Drug: RO4998452; 10mg po daily for 12 weeks; Drug: RO4998452; 20mg po daily for 12 weeks; Drug: RO4998452; 40mg po daily for 12 weeks
Experimental: RO4998452 40mg; 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; 2.5mg po daily for 12 weeks; Drug: RO4998452; 5mg po daily for 12 weeks; Drug: RO4998452; 10mg po daily for 12 weeks; Drug: RO4998452; 20mg po daily for 12 weeks; Drug: RO4998452; 40mg po daily for 12 weeks
Experimental: RO4998452 5mg; 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; 2.5mg po daily for 12 weeks; Drug: RO4998452; 5mg po daily for 12 weeks; Drug: RO4998452; 10mg po daily for 12 weeks; Drug: RO4998452; 20mg po daily for 12 weeks; Drug: RO4998452; 40mg po daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2009
• Primary Completion (Actual): October 28, 2009
• Study Completion (Actual): October 28, 2009

Study Registration Dates

• First Submitted: December 1, 2008
• First Submitted That Met QC Criteria: December 1, 2008
• First Posted (Estimate): December 2, 2008

Study Record Updates

• Last Update Posted (Actual): November 18, 2020
• Last Update Submitted That Met QC Criteria: November 13, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: BC21587; 2008-001249-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).