Randomized, Double-blind, Active-controlled, Study of Rivoglitazone in Type 2 Diabetes Mellitus

NCT ID: NCT00571519

Last Updated: 2021-05-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-14
• Study Completion Date: 2008-05-23

Brief Summary

This is a 26-week, multicenter, randomized, double-blind, placebo and active comparator-controlled, parallel-group study in participants with type 2 diabetes currently sub-optimally controlled by diet and exercise or with non-thiazolidinedione antihyperglycemic monotherapy. Pioglitazone is used as active comparator. The total duration of a participant's participation will be approximately 30 weeks, including a 2-week placebo lead-in period, a 26-week double-blind treatment period, and a 2-week post-treatment follow-up period. Participants who complete the randomized portion of the study per protocol may have the opportunity to continue in a long-term extension study of active treatments.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

rivoglitazone HCl 0.5mg

Group Type: EXPERIMENTAL

Rivoglitazone HCl

Intervention Type: DRUG

0.5 mg tablets administered orally, once daily

metformin

Intervention Type: DRUG

Oral tablets. Rescue medication.

2

rivoglitazone HCl 1.0 mg

Group Type: EXPERIMENTAL

rivoglitazone HCl

Intervention Type: DRUG

1.0 mg tablets administered orally, once daily

metformin

Intervention Type: DRUG

Oral tablets. Rescue medication.

3

rivoglitazone HCl 1.5 mg

Group Type: EXPERIMENTAL

rivoglitazone HCl

Intervention Type: DRUG

1.5 mg tablets administered orally, once daily

metformin

Intervention Type: DRUG

Oral tablets. Rescue medication.

4

placebo matching rivoglitazone HCl tablets

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo tablets matching rivoglitazone tablets administered orally, once daily

metformin

Intervention Type: DRUG

Oral tablets. Rescue medication.

5

pioglitazone HCl 15 mg

Group Type: ACTIVE_COMPARATOR

pioglitazone HCl

Intervention Type: DRUG

15 mg capsules administered orally, once daily

metformin

Intervention Type: DRUG

Oral tablets. Rescue medication.

6

pioglitazone HCl 30 mg

Group Type: ACTIVE_COMPARATOR

pioglitazone HCl

Intervention Type: DRUG

30 mg capsules administered orally, once daily

metformin

Intervention Type: DRUG

Oral tablets. Rescue medication.

7

pioglitazone HCl 45 mg

Group Type: ACTIVE_COMPARATOR

pioglitazone HCl 45 mg

Intervention Type: DRUG

45 mg capsules administered orally, once daily

metformin

Intervention Type: DRUG

Oral tablets. Rescue medication.

8

matching placebo for pioglitazone

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo capsules for pioglitazone administered orally, once daily

metformin

Intervention Type: DRUG

Oral tablets. Rescue medication.

Interventions

Rivoglitazone HCl

0.5 mg tablets administered orally, once daily

Intervention Type: DRUG

rivoglitazone HCl

1.0 mg tablets administered orally, once daily

Intervention Type: DRUG

rivoglitazone HCl

1.5 mg tablets administered orally, once daily

Intervention Type: DRUG

placebo

placebo tablets matching rivoglitazone tablets administered orally, once daily

Intervention Type: DRUG

pioglitazone HCl

15 mg capsules administered orally, once daily

Intervention Type: DRUG

pioglitazone HCl

30 mg capsules administered orally, once daily

Intervention Type: DRUG

pioglitazone HCl 45 mg

45 mg capsules administered orally, once daily

Intervention Type: DRUG

placebo

placebo capsules for pioglitazone administered orally, once daily

Intervention Type: DRUG

metformin

Oral tablets. Rescue medication.

Intervention Type: DRUG

Other Intervention Names

CS-011; CS-011; CS-011

Eligibility Criteria

Inclusion Criteria

• Provided written informed consent at screening.
• Diagnosed with type 2 diabetes mellitus.
• Glycosylated hemoglobin (A1c) >7.0% and ≤8.5% at screening.
• Male or female ≥18 years of age.
• Women of childbearing potential must have been using an adequate method of contraception to avoid pregnancy throughout the study, and for up to 4 weeks after study completion.
• Fasting C-peptide level >0.5 ng/mL at screening.
• Currently being treated with a stable dose of an approved non-thiazolidinedione antihyperglycemic medication (including sulfonylureas, meglitinides, insulin secretagogues, metformin, or α-glucosidase inhibitors) given as monotherapy, for at least 3 months prior to screening, and could discontinue that antihyperglycemic medication at Visit 2 (Week -2) and for the duration of the study. OR
• Untreated and had not taken any antihyperglycemic agent during the 2 months prior to screening; if not treated with an oral antihyperglycemic agent, the participant was considered by the investigator to have failed diet and exercise modification as the sole treatment for type 2 diabetes mellitus.
• Clinically stable in regard to medical conditions other than type 2 diabetes mellitus.
• Concomitant medications (other than oral antihyperglycemic agents) were at stable doses for at least 30 days prior to enrollment and were not anticipated to need adjustment during the study period.

Exclusion Criteria

• History of type 1 diabetes and/or history of ketoacidosis.
• History of long-term (>2 months) therapy with insulin.
• History of prior treatment failure with, or intolerance of, a thiazolidinedione (ie, rosiglitazone, troglitazone, or pioglitazone).
• Treatment with a fibrate lipid-lowering agent (eg, fenofibrate, gemfibrozil).
• Confirmed repeat fasting glucose (≥2 readings of fasting blood glucose) >240 mg/dL (13.3 mmol/L) during the 2-week washout/stabilization and placebo run-in period (Period A).
• Body mass index (BMI) >45 kg/m2 at screening.
• History of weight loss >10% over the 3 months prior to screening.
• Female participant who was pregnant or breastfeeding.
• Systolic blood pressure ≥180 mmHg and/or diastolic blood pressure

≥110 mmHg.

• Any known history of congestive heart failure prior to screening.
• History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, or any revascularization within 6 months prior to screening. History of malignancy (except participants who had been disease-free for >10 years), or whose malignancy was a basal or squamous cell skin carcinoma. Any history of bladder cancer was an exclusion from participation. Women with a history of cervical dysplasia (CIN2 or higher) were to be excluded unless 2 consecutive normal cervical smears had subsequently been recorded prior to enrollment.
• Impaired liver function including evidence of acute or chronic hepatitis or liver disease by medical history, clinical signs or symptoms, or laboratory results.
• Evidence for ongoing infectious liver disease with positive hepatitis A antigen or immunoglobulin M antibody, hepatitis B surface antigen, or antibodies to hepatitis C virus. Participants with normal liver function tests and isolated positive antibodies to hepatitis B virus could have been included.
• Known (or evidence of) infection with human immunodeficiency virus.
• Known hemoglobinopathy or chronic anemia that required specific treatment within 5 years of the screening visit.
• History of alcohol or drug abuse within 1 year prior to screening.
• History of unstable major psychiatric disorders. Known or suspected allergy or hypersensitivity to thiazolidinedione agents.
• Clinically significant abnormalities in any pre-randomization laboratory analyses that, in the investigator's opinion, comprised an undue risk with the participant's participation, or could potentially confound results of the study.

Unexplained hematuria (>3 red blood cells per high-powered field by urine microscopy).

• Blood donation of ≥1 pint (0.5 liter) within the past 30 days prior to screening or plasma donation within 7 days prior to the screening visit (Visit 1).
• Prior known or possible exposure to rivoglitazone.
• Contraindication to treatment with pioglitazone once daily.
• Known or suspected allergy, hypersensitivity, or intolerance to the excipients of the investigational study medication.
• Participation in an interventional medical, surgical, or pharmaceutical study within 30 days prior to the screening visit (Visit 1).
• Any condition or concomitant therapy that, in the opinion of the investigator, might have posed a risk to the participant or made participation not in the participant's best interest.
• A direct or familial relationship with the Sponsor, investigator, or site personnel affiliated with the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Huntsville, Alabama, United States

Huntsville, Alabama, United States

San Diego, California, United States

San Francisco, California, United States

Ridgefield, Connecticut, United States

Fort Lauderdale, Florida, United States

Pembroke Pines, Florida, United States

Port Gibson, Mississippi, United States

Las Vegas, Nevada, United States

Albuquerque, New Mexico, United States

Kettering, Ohio, United States

Fleetwood, Pennsylvania, United States

Harrisburg, Pennsylvania, United States

Simpsonville, South Carolina, United States

Daingerfield, Texas, United States

Dallas, Texas, United States

Plano, Texas, United States

San Antonio, Texas, United States

Countries

United States

Other Identifiers

CS0011-A-U302

Identifier Type: -

Identifier Source: org_study_id