Study of Rivoglitazone in Type 2 Diabetes Mellitus

Phase 3

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: Rivoglitazone
Drug: Placebo
Drug: Pioglitazone

Registration Number: NCT00484198

Lead Sponsor: Daiichi Sankyo

Brief Summary: This is a 26-week study in subjects with type 2 diabetes currently sub-optimally controlled by diet and exercise or with non-thiazolidinedione antihyperglycemic monotherapy. The total duration of a subject's participation will be approximately 30 weeks, including a 2-week placebo run-in period, a 26-week double-blind treatment period, and a 2-week post-treatment follow-up period.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1912

Inclusion Criteria

Diagnosis of type 2 diabetes
Male or female at least 18 years of age
Hemoglobin A1C > 7% and less or equal to 8.5%
Non-fasting C-peptide > 0.5 ng/mL
Current monotherapy treatment with stable dose of approved non-Thiazolidinedione (TZD) antihyperglycemic medication for greater or equal to 3 months prior to screening or
Untreated with any antihyperglycemic agent during 2 months prior to screening

Exclusion Criteria

History of type 1 diabetes or ketoacidosis
History of long-term therapy with insulin
Body Mass Index (BMI) > 45 kg/m^2
Known history of Congestive Heart Failure (CHF)
Impaired hepatic function
History of prior treatment failure with, or intolerance of, a TZD
Contraindication to treatment with pioglitazone
Treatment with fibrates
If untreated with oral antihyperglycemic, considered to have failed diet and exercise modification as the sole treatment for type 2 diabetes

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3	Rivoglitazone	Rivoglitazone 1.5 mg
1	Placebo	-
4	Pioglitazone	Pioglitazone 45 mg
2	Rivoglitazone	Rivoglitazone 1.0 mg

Primary Outcome Measures

Name	Time	Method
Hemoglobin A1c at Baseline and Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to week 26 post-dose	Percentage of hemoglobin A1c (HbA1c) levels are reported.
Change in Hemoglobin A1c From Baseline Through Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 26 weeks post-dose	Percent change in hemoglobin (HbA1c) levels are reported. Greater (negative) percent change indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Homeostasis Model Assessment Index for Insulin Resistance At Baseline To Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to week 26 post-dose	Homeostasis Model Assessment index for Insulin Resistance (HOMA-IR) was calculated as: (fasting insulin concentration \[μU/mL\] x fasting glucose concentration \[mmol/L\])/22.5 Low HOMA-IR scores indicate high insulin sensitivity, whereas high HOMA-IR scores indicate low insulin sensitivity (insulin resistance). A normal HOMA-IR score is \<2.60, HOMA-IR scores 2.60-3.80 are considered "borderline high", and HOMA-IR scores \>3.80 are considered "high" and have correlations of insulin resistance. High HOMA-IR scores indicate worse outcome.
Fasting Plasma Glucose From Baseline Through Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to week 26 post-dose	Normal fasting plasma glucose (FPG) levels are being reported. Normal FPG levels range from 70-110 mg/dL. Lower FPG values indicates better clinical outcome, ie. improvement in FPG.
Change in Fasting Plasma Glucose From Baseline Through Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 26 weeks post-dose	The change in normal fasting plasma glucose (FPG) levels are being reported. A greater (negative) change from baseline indicates an improvement in FPG.
Change in Homeostasis Model Assessment Index for Insulin Resistance At Baseline To Week 26 Endpoint With Last Observation Carried Forward Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 26 weeks post-dose	The change in the Homeostasis Model Assessment index for Insulin Resistance (HOMA-IR) was calculated as: (fasting insulin concentration \[μU/mL\] x fasting glucose concentration \[mmol/L\])/22.5 Low HOMA-IR scores indicate high insulin sensitivity, whereas high HOMA-IR scores indicate low insulin sensitivity (insulin resistance). A normal HOMA-IR score is \<2.60, HOMA-IR scores 2.60-3.80 are considered "borderline high", and HOMA-IR scores \>3.80 are considered "high" and have correlations of insulin resistance. A negative HOMA-IR score indicates an improvement in insulin sensitivity.
Total Cholesterol At Baseline To Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to week 26 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.
Percent Change in Total Cholesterol From Baseline to Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 26 weeks 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. Higher percent change in total cholesterol indicates better outcome, ie. improvement.
Total Triglycerides At Baseline To Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to Week 26 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. Normal triglyceride levels are below 150 mg/dL.
Percent Change in Total Triglycerides From Baseline to Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 26 weeks 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 better outcome, ie. improvement.
Low-Density Lipoprotein Cholesterol At Baseline To Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to Week 26 post-dose	Low-density lipoprotein cholesterol (LDL-C), "bad" cholesterol, is a measure of the total amount of low-density lipoprotein cholesterol in the blood. Normal LDL levels are \<100 mg/dL.
Percent Change in Low-Density Lipoprotein Cholesterol From Baseline to Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 26 weeks post-dose	Low-density lipoprotein cholesterol (LDL-C), "bad" cholesterol, is a measure of the total amount of low-density lipoprotein cholesterol in the blood. A higher percent change indicates improvement.
High-Density Lipoprotein Cholesterol At Baseline To Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline to Week 26 post-dose	High-density lipoprotein cholesterol (HDL-C), "good" cholesterol, is a measure of the total amount of high-density lipoprotein cholesterol in the blood. Normal HDL levels are \>40 mg/dL.
Percent Change in High-Density Lipoprotein Cholesterol From Baseline to Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline to 26 weeks post-dose	High-density lipoprotein cholesterol (HDL-C), "good" cholesterol, is a measure of the total amount of high-density lipoprotein cholesterol in the blood. A higher percent change indicates improvement.
Apolipoprotein A-I At Baseline To Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline to Week 26 post-dose	Apolipoprotein (Apo) A-I levels, a measure of the total amount of Apolipoprotein (Apo) A-I in the blood, are being reported. Normal Apo A-1 levels range from 120-140 mg/dL.
Percent Change in Apolipoprotein A-I From Baseline to Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 26 weeks post-dose	Apolipoprotein (Apo) A-I is a measure of the total amount of Apolipoprotein (Apo) A-I in the blood. Decreased ApoA-1 levels are associated with poor clinical outcome. A lower percent change in ApoA-1 levels indicates an improvement in clinical outcome.
Apolipoprotein B At Baseline To Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline to Week 26 post-dose	Apolipoprotein (Apo) B, a measure of the total amount of Apo B in the blood, is being reported. Normal Apo B levels are \<100 mg/dL.
Percent Change in Apolipoprotein B From Baseline to Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 26 weeks post-dose	Apolipoprotein (Apo) B, a measure of the total amount of Apo B in the blood, is being reported. A greater (negative) percent change in ApoB levels indicated an improvement in clinical outcome.
Hemoglobin A1c at Baseline and Week 52 Extension Period Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to Week 52 post-dose	Percentage of hemoglobin A1c (HbA1c) levels are reported.
Change in Hemoglobin A1c From Baseline Through Week 52 Extension Period Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 52 weeks post-dose	Change in hemoglobin (HbA1c) levels are reported. Greater (negative) percent change indicates improvement.
Fasting Plasma Glucose From Baseline Through Week 52 Extension Period Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to Week 52 post-dose	Normal fasting plasma glucose (FPG) levels are being reported. Normal FPG levels range from 70-110 mg/dL. Lower FPG values indicates better clinical outcome, ie. improvement in FPG.
Change in Fasting Plasma Glucose From Baseline Through Week 52 Extension Period Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Baseline up to 52 weeks post-dose	The change in normal fasting plasma glucose (FPG) levels are being reported. A greater (negative) change from baseline indicates an improvement in FPG.
Drug-Related Treatment-Emergent Adverse Events Reported by ≥1% Participants Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus	Week -2 up to Week 52 post-dose	Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that occurred on or after the first dose of double-blind study medication, and ongoing AEs that started prior to the first dose of double-blind study medication and increased in severity on or after the first dose of double-blind study medication.