Clinical trial NCT02139943: A Study of Effects of Canagliflozin as Add-on Therapy to Insulin in the Treatment of Participants With Type 1 Diabetes Mellitus (T1DM)
Official title: A Randomized Phase 2, Double-blind, Placebo-controlled, Treat-to-Target, Parallel-group, 3-arm, Multicenter Study to Assess the Efficacy and Safety of Canagliflozin as Add-on Therapy to Insulin in the Treatment of Subjects With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes Mellitus, Type 1
Canagliflozin
Continuous Glucose Monitoring
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-05-16
Enrollment: 352
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
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 assess the effects of administration of canagliflozin 100 mg and 300 mg, compared with placebo as an addition to insulin therapy for the treatment of Type 1 Diabetes Mellitus (T1DM).

Detailed description: This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled (an inactive substance that is compared with a medication to test whether the medication has a real effect) parallel-group, multicenter study of canagliflozin as an addition to insulin therapy for participants with type 1 diabetes mellitus and inadequate glycemic control.

Approximately 330 participants will be randomly assigned in a 1:1:1 ratio to either canagliflozin 100 mg, canagliflozin 300 mg, or placebo groups. About 90 participants (30 per treatment group) will be selected for a substudy with a purpose of a continuous glucose monitoring (CGM) assessment for 7 days at baseline and 7 days at the end of treatment.

The total duration of the participation will be about 22 weeks, during which participants will need to return to investigational sites for approximately 9 visits. During the study participants will receive advice on treatment of hypoglycemia and diabetic ketoacidosis (DKA), as well as on compliance with diet and exercise.

Eligibility criteria: Inclusion Criteria:

* Must have type 1 diabetes mellitus (T1DM) for at least 1 year
* Must have have inadequate glycemic control (as defined by glycosylated hemoglobin level of \>= 7.0% to \<= 9.0%) on basal plus bolus insulin at screening
* Must have body mass index 21 to 35 kg/m2 inclusive
* Must be on a total daily dose of insulin \>= 0.6 IU/kg at screening
* Must be on a stable insulin regimen for at least 8 weeks prior to screening

Exclusion Criteria:

* History of T2DM, pancreas or β-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
* Severe hypoglycemia (defined as an event required assistance from another person, or which resulted in seizure or loss of consciousness) within 6 months prior to study start
* Diabetic ketoacidosis within 6 months prior to study start
* History of hereditary glucose-galactose malabsorption or primary renal glycosuria
* An ongoing, inadequately controlled thyroid disorder

Primary outcomes:
measure: Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight
timeFrame: Week 18
measure: Percentage of Participants With Adverse Events
timeFrame: Up to 22 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Concord
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Gatos
country: United States
state: California
city: Northridge
country: United States
state: California
city: Orange
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Temecula
country: United States
state: California
city: Tustin
country: United States
state: California
city: Ventura
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Council Bluffs
country: United States
state: Iowa
city: Des Moines
country: United States
state: Iowa
city: Baton Rouge
country: United States
state: Louisiana
city: Rockville
country: United States
state: Maryland
city: Billings
country: United States
state: Montana
city: Omaha
country: United States
state: Nebraska
city: El Paso
country: United States
state: Nevada
city: Las Vegas
country: United States
state: Nevada
city: Nashua
country: United States
state: New Hampshire
city: Billings
country: United States
state: New York
city: Smithtown
country: United States
state: New York
city: Morehead City
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Mentor
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Greer
country: United States
state: South Carolina
city: Bloomington
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Schertz
country: United States
state: Texas
city: Tomball
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Spokane
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Calgary
country: Canada
state: Alberta
city: London
country: Canada
state: Ontario
city: Oakville
country: Canada
state: Ontario
city: Thornhill
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Laval
country: Canada
state: Quebec
city: Sainte-Foy
country: Canada
state: Quebec
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Rodbard HW, Peters AL, Slee A, Cao A, Traina SB, Alba M. The Effect of Canagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, on Glycemic End Points Assessed by Continuous Glucose Monitoring and Patient-Reported Outcomes Among People With Type 1 Diabetes. Diabetes Care. 2017 Feb;40(2):171-180. doi: 10.2337/dc16-1353. Epub 2016 Nov 29.
citation: Peters AL, Henry RR, Thakkar P, Tong C, Alba M. Diabetic Ketoacidosis With Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, in Patients With Type 1 Diabetes. Diabetes Care. 2016 Apr;39(4):532-8. doi: 10.2337/dc15-1995.
citation: Henry RR, Thakkar P, Tong C, Polidori D, Alba M. Efficacy and Safety of Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, as Add-on to Insulin in Patients With Type 1 Diabetes. Diabetes Care. 2015 Dec;38(12):2258-65. doi: 10.2337/dc15-1730. Epub 2015 Oct 20.