Study of Rivoglitazone in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Placebo
* Drug: Rivoglitazone
* Drug: Rivoglitazone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: 1<br> | Drug: Placebo<br>* Rivoglitazone-matching placebo administered as a tablet orally, once daily or a pioglitazone-matching placebo administered as an over-encapsulated tablet orally, once daily capsule<br>|
| Experimental: 2<br>Rivoglitazone 1.0 mg | Drug: Rivoglitazone<br>* 1.0 mg tablet administered orally, once daily<br>|
| Experimental: 3<br>Rivoglitazone 1.5 mg | Drug: Rivoglitazone<br>* 1.5 mg tablet administered orally, once daily<br>|
| Active Comparator: 4<br>Pioglitazone 45 mg | Drug: Pioglitazone<br>* 45 mg over-encapsulated tablet administered orally, once daily<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Percentage of hemoglobin A1c (HbA1c) levels are reported. | Baseline up to week 26 post-dose | 
| 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 | Percent change in hemoglobin (HbA1c) levels are reported. Greater (negative) percent change indicates improvement. | Baseline up to 26 weeks post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Baseline up to week 26 post-dose | 
| 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 | The change in normal fasting plasma glucose (FPG) levels are being reported. A greater (negative) change from baseline indicates an improvement in FPG. | Baseline up to 26 weeks post-dose | 
| 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 | 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. | Baseline up to week 26 post-dose | 
| 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 | 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. | Baseline up to 26 weeks post-dose | 
| 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 | 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. | Baseline up to week 26 post-dose | 
| 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 | 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. | Baseline up to 26 weeks post-dose | 
| 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 | 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. | Baseline up to Week 26 post-dose | 
| 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 | 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. | Baseline up to 26 weeks post-dose | 
| 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 | 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. | Baseline up to Week 26 post-dose | 
| 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 | 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. | Baseline up to 26 weeks post-dose | 
| 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 | 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. | Baseline to Week 26 post-dose | 
| 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 | 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. | Baseline to 26 weeks post-dose | 
| 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 | 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. | Baseline to Week 26 post-dose | 
| 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 | 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. | Baseline up to 26 weeks post-dose | 
| 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 | 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. | Baseline to Week 26 post-dose | 
| 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 | 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. | Baseline up to 26 weeks post-dose | 
| Hemoglobin A1c at Baseline and Week 52 Extension Period Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus | Percentage of hemoglobin A1c (HbA1c) levels are reported. | Baseline up to Week 52 post-dose | 
| 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 | Change in hemoglobin (HbA1c) levels are reported. Greater (negative) percent change indicates improvement. | Baseline up to 52 weeks post-dose | 
| 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 | 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. | Baseline up to Week 52 post-dose | 
| 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 | The change in normal fasting plasma glucose (FPG) levels are being reported. A greater (negative) change from baseline indicates an improvement in FPG. | Baseline up to 52 weeks post-dose | 
| 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 | 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. | Week -2 up to Week 52 post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus