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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00571519
Recruitment Status : Terminated (DSPD focusing on Study 301 to confirm the clinical profile before proceeding. Daiichi Sankyo Pharma Development terminated this study on 23 Apr 2008 because of changes in the clinical development plan with 94 of 2600 planned, randomized participants.)
First Posted : December 12, 2007
Results First Posted : February 26, 2021
Last Update Posted : May 26, 2021
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Rivoglitazone HCl Drug: rivoglitazone HCl Drug: placebo Drug: pioglitazone HCl Drug: pioglitazone HCl 45 mg Drug: metformin Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 94 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo, and Active Comparator-controlled, Parallel-group Study of the Efficacy and Safety of Rivoglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus
Actual Study Start Date : November 14, 2007
Actual Primary Completion Date : May 23, 2008
Actual Study Completion Date : May 23, 2008

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1
rivoglitazone HCl 0.5mg
Drug: Rivoglitazone HCl
0.5 mg tablets administered orally, once daily
Other Name: CS-011

Drug: metformin
Oral tablets. Rescue medication.

Experimental: 2
rivoglitazone HCl 1.0 mg
Drug: rivoglitazone HCl
1.0 mg tablets administered orally, once daily
Other Name: CS-011

Drug: metformin
Oral tablets. Rescue medication.

Experimental: 3
rivoglitazone HCl 1.5 mg
Drug: rivoglitazone HCl
1.5 mg tablets administered orally, once daily
Other Name: CS-011

Drug: metformin
Oral tablets. Rescue medication.

Placebo Comparator: 4
placebo matching rivoglitazone HCl tablets
Drug: placebo
placebo tablets matching rivoglitazone tablets administered orally, once daily

Drug: metformin
Oral tablets. Rescue medication.

Active Comparator: 5
pioglitazone HCl 15 mg
Drug: pioglitazone HCl
15 mg capsules administered orally, once daily

Drug: metformin
Oral tablets. Rescue medication.

Active Comparator: 6
pioglitazone HCl 30 mg
Drug: pioglitazone HCl
30 mg capsules administered orally, once daily

Drug: metformin
Oral tablets. Rescue medication.

Active Comparator: 7
pioglitazone HCl 45 mg
Drug: pioglitazone HCl 45 mg
45 mg capsules administered orally, once daily

Drug: metformin
Oral tablets. Rescue medication.

Placebo Comparator: 8
matching placebo for pioglitazone
Drug: placebo
placebo capsules for pioglitazone administered orally, once daily

Drug: metformin
Oral tablets. Rescue medication.




Primary Outcome Measures :
  1. Change in A1c From Baseline Through Week 20 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 2, week 4, week 6, week 8, week 10, week 12, week 16, and week 20 post-dose. ]
    Glycosylated hemoglobin (A1c) levels and mean changes in A1c were used to measure glycemic control. A1c categorical targets are <7.0% and <6.5%.


Secondary Outcome Measures :
  1. Change in Fasting Plasma Glucose From Baseline Through Week 20 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 2, week 4, week 6, week 8, week 12, week 16, and week 20 post-dose. ]
    Normal fasting plasma glucose (FPG) -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline and a lower FPG means improvement.

  2. Change in Total Cholesterol From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Total cholesterol is a measure of the total amount of cholesterol in the blood, including low-density lipoprotein cholesterol (LDL-C) - the "bad" cholesterol, high-density lipoprotein cholesterol (HDL-C) - the "good" cholesterol, and triglycerides. The equation to calculate total cholesterol is: LDL + HDL + (triglycerides/5) = total cholesterol.

  3. Percent Change in Total Cholesterol From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Total cholesterol is a measure of the total amount of cholesterol in the blood, including low-density lipoprotein cholesterol (LDL-C) - the "bad" cholesterol, high-density lipoprotein cholesterol (HDL-C) - the "good" cholesterol, and triglycerides. The equation to calculate total cholesterol is: LDL + HDL + (triglycerides/5) = total cholesterol.

  4. Change in Total Triglycerides From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Total Triglycerides (TG) is a measure of the total amount of triglycerides in the blood. The equation to calculate total triglycerides is: (total cholesterol-Low-density Lipoprotein cholesterol (LDL- C) - High-density lipoprotein cholesterol (HDL- C)) x 5 = Total Triglycerides. A negative change means improvement.

  5. Percent Change in Total Triglycerides From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Total Triglycerides (TG) is a measure of the total amount of triglycerides in the blood. The equation to calculate total triglycerides is: (total cholesterol-Low-density Lipoprotein cholesterol (LDL- C) - High-density lipoprotein cholesterol (HDL- C)) x 5 = Total Triglycerides. A negative change means improvement.

  6. Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Low-density lipoprotein cholesterol (LDL-C) is a measure of the total amount of low-density lipoprotein cholesterol in the blood. LDL-C was measured as part of the fasting lipid panel. LDL-C is considered "bad" cholesterol, so a lower score (negative change) means improvement.

  7. Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Low-density lipoprotein cholesterol (LDL-C) is a measure of the total amount of low-density lipoprotein cholesterol in the blood. LDL-C was measured as part of the fasting lipid panel. LDL-C is considered "bad" cholesterol, so a lower score (negative change) means improvement.

  8. Change in High-Density Lipoprotein Cholesterol From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    High-density lipoprotein cholesterol (HDL-C) is a measure of the total amount of high-density lipoprotein cholesterol in the blood. HDL-C was measured as part of the fasting lipid panel. HDL-C is considered "good" cholesterol, so a higher score (positive change) means improvement.

  9. Percent Change in High-Density Lipoprotein Cholesterol From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    High-density lipoprotein cholesterol (HDL-C) is a measure of the total amount of high-density lipoprotein cholesterol in the blood. HDL-C was measured as part of the fasting lipid panel. HDL-C is considered "good" cholesterol, so a higher score (positive change) means improvement.

  10. Change in Apolipoprotein (Apo) A-I From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Apolipoprotein (Apo) A-I is a measure of the total amount of Apolipoprotein (Apo) A-I in the blood. Apo A-I was measured as part of the fasting lipid panel.

  11. Percent Change in Apolipoprotein (Apo) A-I From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Apolipoprotein (Apo) A-I is a measure of the total amount of Apolipoprotein (Apo) A-I in the blood. Apo A-I was measured as part of the fasting lipid panel.

  12. Change in Apolipoprotein (Apo) B From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Apolipoprotein (Apo) B is a measure of the total amount of Apolipoprotein (Apo) B in the blood. Apo B was measured as part of the fasting lipid panel.

  13. Percent Change in Apolipoprotein (Apo) B From Baseline Through Week 12 Following Rivoglitazone Compared to Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 12 post-dose. ]
    Apolipoprotein (Apo) B is a measure of the total amount of Apolipoprotein (Apo) B in the blood. Apo B was measured as part of the fasting lipid panel.

  14. Number of Participants With Treatment-Emergent Adverse Events by System Organ Class and Preferred Term Following Rivoglitazone or Pioglitazone as Monotherapy Treatment of Type 2 Diabetes Mellitus [ Time Frame: Baseline up to week 26 post-dose, approximately a total of 27 weeks. ]
    Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that occurred on or after the first dose of randomized study medication and ongoing adverse events that started prior to the first dose of randomized study medication and increased in severity on or after the first dose of randomized study medication.



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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00571519


Locations
Layout table for location information
United States, Alabama
Huntsville, Alabama, United States, 35801
Huntsville, Alabama, United States, 35802
United States, California
San Diego, California, United States, 92128
San Francisco, California, United States, 94115
United States, Connecticut
Ridgefield, Connecticut, United States, 06877
United States, Florida
Fort Lauderdale, Florida, United States, 33308
Pembroke Pines, Florida, United States, 33026
United States, Mississippi
Port Gibson, Mississippi, United States, 39150
United States, Nevada
Las Vegas, Nevada, United States, 89119
United States, New Mexico
Albuquerque, New Mexico, United States, 87109
United States, Ohio
Kettering, Ohio, United States, 45429
United States, Pennsylvania
Fleetwood, Pennsylvania, United States, 19522
Harrisburg, Pennsylvania, United States, 17112
United States, South Carolina
Simpsonville, South Carolina, United States, 29681
United States, Texas
Daingerfield, Texas, United States, 75638
Dallas, Texas, United States, 75216
Plano, Texas, United States, 75093
San Antonio, Texas, United States, 78205
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
Layout table for investigator information
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT00571519    
Other Study ID Numbers: CS0011-A-U302
First Posted: December 12, 2007    Key Record Dates
Results First Posted: February 26, 2021
Last Update Posted: May 26, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs