A Safety and Efficacy Study of Canagliflozin in Older Patients (55 to 80 Years of Age) With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01106651
First received: April 1, 2010
Last updated: August 1, 2014
Last verified: August 2014

April 1, 2010
August 1, 2014
June 2010
November 2011   (final data collection date for primary outcome measure)
Change in HbA1c From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
To assess the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c). [ Time Frame: After 26 weeks of treatment with study drug. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01106651 on ClinicalTrials.gov Archive Site
  • Percentage of Patients With HbA1c <7% at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    The table below shows the percentage of patients with HbA1c <7% at Week 26 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.
  • Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
  • Percent Change in Body Weight From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
  • Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean change in total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
  • Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    Region percent total fat = body fat as a percentage of (body fat + lean body mass + bone mass content). The table below shows the least-squares (LS) mean change in region percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific dual-energy X-ray absorptiometry (DXA) analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
  • Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    Tissue percent total fat = body fat as a percentage of body fat + lean body mass. The table below shows the least-squares (LS) mean change in tissue percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition . The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
  • Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
  • Percent Change in Triglycerides From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
  • Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
    The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 or each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
  • Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: Yes ]
    The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in lumbar spine BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change.
  • Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: Yes ]
    The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in distal forearm BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change.
  • Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: Yes ]
    The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in femoral neck BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change.
  • Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: Yes ]
    The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in total hip BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change.
  • To assess the effect of study drug on bone mineral density as measured by dual-energy X-ray absorptiometry (DXA) [ Time Frame: After 26, 52 and 104 weeks of treatment ] [ Designated as safety issue: Yes ]
  • To assess the effect of study drug on bone strength as measured by Quantitative Computerized Tomography (QCT) in a subgroup of patients [ Time Frame: After 52 weeks of treatment ] [ Designated as safety issue: Yes ]
  • To assess the effect of study drug on markers of bone turnover [ Time Frame: After 12 and 26 weeks of treatment ] [ Designated as safety issue: Yes ]
  • To assess the effect of study drug on body composition (eg total fat mass) as measured by DXA [ Time Frame: After 26 weeks of treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Safety and Efficacy Study of Canagliflozin in Older Patients (55 to 80 Years of Age) With Type 2 Diabetes Mellitus
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin Compared With Placebo in the Treatment of Older Subjects With Type 2 Diabetes Mellitus Inadequately Controlled on Glucose Lowering Therapy

The purpose of this study is to evaluate the efficacy and safety of 2 different doses of canagliflozin compared with placebo in older patients (55 to 80 years of age) with type 2 diabetes mellitus (T2DM) with inadequate control on their current diabetes treatment regimen.

Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double-blind (neither the patient or the study doctor will know the name of the assigned treatment), placebo-controlled, parallel-group, 3-arm (3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the other treatments but has no real medicine) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy to control their diabetes. Approximately 720 older (55 to 80 years of age) patients with T2DM who are either not on an antihyperglycemic agent or who are receiving treatment with a stable regimen of antihyperglycemic agent(s) and have inadequate glycemic (blood sugar) control will receive once daily treatment with canagliflozin (100 mg or 300 mg) or placebo capsules for 104 weeks (includes 26 weeks of double-blind treatment followed by a 78-week extension period). In addition, all patients will take stable doses of the antihyperglycemic agent(s) that they were taking before entry in the study for the duration of the study. Patients will participate in the study for approximately 108 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, the patient will receive treatment with an antihyperglycemic agent (rescue therapy) that is considered clinically appropriate and consistent with local prescribing information. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, measures of bone health, 12-lead electrocardiograms (ECGs), vital signs measurements, body weight, physical examinations, and self-monitored blood glucose (SMGB) measurements. The primary outcome measure in the study is the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 weeks of treatment. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. All patients will take single-blind placebo capsules for 2 weeks before randomization. After randomization, patients will take double blind canagliflozin (100 mg or 300 mg) or matching placebo for 104 weeks.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Diabetes Mellitus, Type 2
  • Drug: Canagliflozin 100 mg
    One 100 mg over-encapsulated tablet orally (by mouth) once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
  • Drug: Canagliflozin 300 mg
    One 300 mg over-encapsulated tablet orally (by mouth) once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
  • Drug: Antihyperglycemic agent(s)
    Stable doses of antihyperglycemic agents (sulfonylurea agent, thiazolidinediones, dipeptidyl peptidase 4 [DPP-4] inhibitors, metformin, insulin [all types]) and their combinations (sulfonylurea agent and insulin [all types], metformin and insulin [all types], metformin and sulfonylurea, alpha glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 [DPP-4]) are used as per protocol specifications.
  • Drug: Placebo
    One matching placebo capsule orally once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
  • Experimental: Canagliflozin 100 mg
    Each patient will receive 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
    Interventions:
    • Drug: Canagliflozin 100 mg
    • Drug: Antihyperglycemic agent(s)
  • Experimental: Canagliflozin 300 mg
    Each patient will receive 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
    Interventions:
    • Drug: Canagliflozin 300 mg
    • Drug: Antihyperglycemic agent(s)
  • Placebo Comparator: Placebo
    Each patient will receive matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
    Interventions:
    • Drug: Antihyperglycemic agent(s)
    • Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
716
May 2013
November 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • All patients must have a diagnosis of T2DM and may be currently treated with a stable regimen of antihyperglycemic agent(s)
  • Patients in the study must have a HbA1c between >=7 and <=10.0%
  • Patients must have a fasting plasma glucose (FPG) <270 mg/dL (15 mmol/L)

Exclusion Criteria:

  • History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy, or a severe hypoglycemic episode within 6 months before screening
Both
55 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Colombia,   France,   Greece,   Hong Kong,   India,   New Zealand,   Poland,   Romania,   South Africa,   Spain,   Sweden,   Switzerland,   Ukraine,   United Kingdom
 
NCT01106651
CR017014, 28431754DIA3010
Yes
Janssen Research & Development, LLC
Janssen Research & Development, LLC
Not Provided
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Janssen Research & Development, LLC
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP