Study of Rivoglitazone in Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00484198
• Other study ID #: CS0011-A-U301
• Secondary ID: 2006-005047-28
• Status: Completed
• Phase: Phase 3
• Start date: April 23, 2007
• Est. completion date: February 12, 2009

Study information

• Verified date: July 2021
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1912
• Est. completion date: February 12, 2009
• Est. primary completion date: February 12, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Pioglitazone
45 mg over-encapsulated tablet administered orally, once daily
• Placebo
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
• Rivoglitazone
1.0 mg tablet administered orally, once daily
• Rivoglitazone
1.5 mg tablet administered orally, once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Chile,  Czechia,  Germany,  Hungary,  India,  Latvia,  Mexico,  Peru,  Puerto Rico,  Romania,  Serbia,  Slovakia,  South Africa,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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