Clinical trial NCT01106651: A Safety and Efficacy Study of Canagliflozin in Older Patients (55 to 80 Years of Age) With Type 2 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Canagliflozin
Placebo
Hemoglobin A1c
Bone
Type 2 diabetes mellitus
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2010-04-20
Enrollment: 716
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
Secondary outcomes:
measure: Percentage of Patients With HbA1c <7% at Week 26
timeFrame: Week 26
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Body Weight From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: 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
timeFrame: Day 1 (Baseline) and Week 26
measure: 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
timeFrame: Day 1 (Baseline) and Week 26
measure: 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
timeFrame: Day 1 (Baseline) and Week 26
measure: Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Triglycerides From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
measure: Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26
timeFrame: Day 1 (Baseline) and Week 26
Other outcomes:
Locations:
city: Glendale
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Carmichael
country: United States
state: California
city: Citrus Heights
country: United States
state: California
city: Fair Oaks
country: United States
state: California
city: Roseville
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Daytona Beach
country: United States
state: Florida
city: Fleming Island
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Wichita
country: United States
state: Kansas
city: Waltham
country: United States
state: Massachusetts
city: Pahrump
country: United States
state: Nevada
city: Albuquerque
country: United States
state: New Mexico
city: Cary
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Bismarck
country: United States
state: North Dakota
city: Franklin
country: United States
state: Ohio
city: Mount Pleasant
country: United States
state: South Carolina
city: Bristol
country: United States
state: Tennessee
city: Carrollton
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: Richardson
country: United States
state: Texas
city: Renton
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Wenatchee
country: United States
state: Washington
city: Fremantle
country: Australia
city: Heidelberg Heights
country: Australia
city: Meadowbrook
country: Australia
city: Richmond
country: Australia
city: Vancouver
country: Canada
state: British Columbia
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: Barrie
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Markham
country: Canada
state: Ontario
city: Oakville
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Barranquilla
country: Colombia
city: Bogota
country: Colombia
city: Corbeil Essonnes
country: France
city: Paris
country: France
city: Venissieux
country: France
city: Thessalonikis
country: Greece
city: Thessaloniki
country: Greece
city: Sha Tin
country: Hong Kong
city: Bangalore
country: India
city: Nagpur
country: India
city: Pune
country: India
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Tauranga
country: New Zealand
city: Wellington
country: New Zealand
city: Katowice
country: Poland
city: Krakow
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Bucharest
country: Romania
city: Sibiu
country: Romania
city: Pretoria
country: South Africa
city: Granada
country: Spain
city: Madrid
country: Spain
city: Pozuelo De Alarcon
country: Spain
city: Sevilla
country: Spain
city: Göteborg
country: Sweden
city: Uppsala
country: Sweden
city: Bruderholz
country: Switzerland
city: St Gallen
country: Switzerland
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Birmingham
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Liverpool
country: United Kingdom
city: Manchester
country: United Kingdom
city: Reading
country: United Kingdom
city: Salford
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Januzzi JL Jr, Butler J, Jarolim P, Sattar N, Vijapurkar U, Desai M, Davies MJ. Effects of Canagliflozin on Cardiovascular Biomarkers in Older Adults With Type 2 Diabetes. J Am Coll Cardiol. 2017 Aug 8;70(6):704-712. doi: 10.1016/j.jacc.2017.06.016. Epub 2017 Jun 12.
citation: Qiu R, Balis D, Xie J, Davies MJ, Desai M, Meininger G. Longer-term safety and tolerability of canagliflozin in patients with type 2 diabetes: a pooled analysis. Curr Med Res Opin. 2017 Mar;33(3):553-562. doi: 10.1080/03007995.2016.1271780. Epub 2017 Jan 4.
citation: Blonde L, Stenlof K, Fung A, Xie J, Canovatchel W, Meininger G. Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks. Postgrad Med. 2016 May;128(4):371-80. doi: 10.1080/00325481.2016.1169894. Epub 2016 Apr 7.
citation: Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2016 Jan;101(1):157-66. doi: 10.1210/jc.2015-3167. Epub 2015 Nov 18.
citation: 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.
citation: 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.
citation: 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.
citation: 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.