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

NCT ID: NCT01106651

Last Updated: 2014-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 716 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2013-05-31

Brief Summary

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.

Detailed Description

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Canagliflozin 100 mg

Intervention Type: DRUG

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.

Antihyperglycemic agent(s)

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Canagliflozin 300 mg

Intervention Type: DRUG

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.

Antihyperglycemic agent(s)

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Antihyperglycemic agent(s)

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Glendale, Arizona, United States

Phoenix, Arizona, United States

Little Rock, Arkansas, United States

Carmichael, California, United States

Citrus Heights, California, United States

Fair Oaks, California, United States

Roseville, California, United States

Sacramento, California, United States

San Diego, California, United States

Walnut Creek, California, United States

Daytona Beach, Florida, United States

Fleming Island, Florida, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Atlanta, Georgia, United States

Wichita, Kansas, United States

Waltham, Massachusetts, United States

Pahrump, Nevada, United States

Albuquerque, New Mexico, United States

Cary, North Carolina, United States

Charlotte, North Carolina, United States

Wilmington, North Carolina, United States

Bismarck, North Dakota, United States

Franklin, Ohio, United States

Mt. Pleasant, South Carolina, United States

Bristol, Tennessee, United States

Carrollton, Texas, United States

Dallas, Texas, United States

Irving, Texas, United States

Plano, Texas, United States

Richardson, Texas, United States

Renton, Washington, United States

Tacoma, Washington, United States

Wenatchee, Washington, United States

Fremantle, , Australia

Heidelberg Heights, , Australia

Meadowbrook, , Australia

Richmond, , Australia

Vancouver, British Columbia, Canada

St. John's, Newfoundland and Labrador, Canada

Barrie, Ontario, Canada

London, Ontario, Canada

Markham, Ontario, Canada

Oakville, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Barranquilla, , Colombia

Bogotá, , Colombia

Corbeil-Essonnes, , France

Paris, , France

Vénissieux, , France

Thessaloniki, , Greece

Thessalonikis, , Greece

Shatin, , Hong Kong

Bangalore, , India

Nagpur, , India

Pune, , India

Auckland, , New Zealand

Christchurch, , New Zealand

Tauranga, , New Zealand

Wellington, , New Zealand

Katowice, , Poland

Krakow, , Poland

Torun, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Bucharest, , Romania

Sibiu, , Romania

Pretoria, , South Africa

Granada, , Spain

Madrid, , Spain

Pozuelo de Alarcón, , Spain

Seville, , Spain

Gothenburg, , Sweden

Uppsala, , Sweden

Bruderholz, , Switzerland

Sankt Gallen, , Switzerland

Kharkiv, , Ukraine

Kiev, , Ukraine

Birmingham, , United Kingdom

Cardiff, , United Kingdom

Glasgow, , United Kingdom

Liverpool, , United Kingdom

Manchester, , United Kingdom

Reading, , United Kingdom

Salford, , United Kingdom

Countries

United States; Australia; Canada; Colombia; France; Greece; Hong Kong; India; New Zealand; Poland; Romania; South Africa; Spain; Sweden; Switzerland; Ukraine; United Kingdom

References

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Reference Type: DERIVED

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Reference Type: DERIVED

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Reference Type: DERIVED

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Reference Type: DERIVED

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Bilezikian JP, Watts NB, Usiskin K, Polidori D, Fung A, Sullivan D, Rosenthal N. Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin. J Clin Endocrinol Metab. 2016 Jan;101(1):44-51. doi: 10.1210/jc.2015-1860. Epub 2015 Nov 18.

Reference Type: DERIVED

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Weir MR, Kline I, Xie J, Edwards R, Usiskin K. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR). Curr Med Res Opin. 2014 Sep;30(9):1759-68. doi: 10.1185/03007995.2014.919907. Epub 2014 May 22.

Reference Type: DERIVED

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Nyirjesy P, Sobel JD, Fung A, Mayer C, Capuano G, Ways K, Usiskin K. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin. 2014 Jun;30(6):1109-19. doi: 10.1185/03007995.2014.890925. Epub 2014 Feb 21.

Reference Type: DERIVED

PMID: 24517339 (View on PubMed)

Bode B, Stenlof K, Sullivan D, Fung A, Usiskin K. Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: a randomized trial. Hosp Pract (1995). 2013 Apr;41(2):72-84. doi: 10.3810/hp.2013.04.1020.

Reference Type: DERIVED

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Other Identifiers

28431754DIA3010

Identifier Type: OTHER

Identifier Source: secondary_id

CR017014

Identifier Type: -

Identifier Source: org_study_id