A Study to Assess Electrocardiogram Results in Healthy Volunteers Receiving Canagliflozin (JNJ-28431754)

Johnson & Johnson (J&J)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Canagliflozin (JNJ-28431754); Drug: Placebo; Drug: Moxifloxacin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01787357

28431754DIA1010 (Other Identifier)

CR015514

Details and patient eligibility

About

The purpose of this study is to assess the effect of canagliflozin (JNJ-28431754) on electrocardiogram results (recordings of the electrical activity of the heart) in healthy volunteers after a single therapeutic dose (300 mg) and a single supra-therapeutic dose (4 times higher [1,200 mg] than the anticipated therapeutic dose of 300 mg). The safety and tolerability of canagliflozin will also be assessed.

Full description

This study will be a randomized (the treatment is assigned by chance), single-center, double-blind (neither investigator nor volunteer knows the identity of the assigned treatment), double-dummy (a technique for retaining the blinded nature of the study when the treatments do not look identical), placebo-controlled (one of the treatments is inactive), positive-controlled (one of the treatments has a known potential effect on electrocardiogram results), four-way cross-over study (all volunteers will receive each of the 4 treatments but in a different order) to assess the effect of canagliflozin (a drug currently being investigated for the treatment of type 2 diabetes mellitus) on electrocardiogram results in healthy volunteers. The study will consist of 3 phases: a screening phase, a double-blind treatment phase, and an end-of study (or follow-up) phase. Volunteers will be assigned to 1 of 4 treatment sequence groups (ADBC, DABC, BCDA, or CDAB). The treatment sequence will be decided by randomization. Treatment A will be a single dose of 300 mg of canagliflozin. Treatment B will be a single dose of 1,200 mg of canagliflozin. Treatment C will be a single dose of placebo (inactive medication). Treatment D will be a single dose of 400 mg of moxifloxacin (an antibiotic with known potential to affect electrocardiogram results). Each treatment will be given during a treatment period of 2 days duration; each treatment period will be separated by a washout period (when no medication is given) of 10 to 14 days. Each volunteer will participate in the study for approximately 61 days.

Enrollment: 60 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Volunteers must have a body mass index (BMI = weight in kg/height in m2) between 18 and 35 kg/m2 (inclusive) and body weight not less than 50 kg
• Volunteers must have an average of triplicate 12-lead electrocardiogram (ECG) recordings, taken with a maximum of 2 minutes between recordings, consistent with normal cardiac conduction and function, as specified by the protocol
• Volunteers must be non-smokers

Exclusion criteria

• History of or currently active illness considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the patient from the study or that could interfere with the interpretation of the study results
• History of additional risk factors for the presence of a family history of Short QT Syndrome, Long QT Syndrome, sudden unexplained death at a young age (<=40 years), drowning or sudden infant death syndrome in a first degree relative (ie, biological parent, sibling, or child)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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60 participants in 4 patient groups

Sequence 1 (ADBC)

Experimental group

Description:

Each volunteer will receive Treatment A on Day 1 of Treatment Period 1, followed by Treatment D on Day 1 of Treatment Period 2, followed by Teatment B on Day 1 of Treatment Period 3, and followed by Treatment C on Day 1 of Treatment Period 4. Each treatment period will be 2 days in duration and there will be a washout period (with no medication) of 10 to 14 days between each treatment period.

Treatment:

Drug: Moxifloxacin

Drug: Placebo

Drug: Canagliflozin (JNJ-28431754)

Sequence 2 (BACD)

Experimental group

Description:

Each volunteer will receive Treatment B on Day 1 of Treatment Period 1, followed by Treatment A on Day 1 of Treatment Period 2, followed by Treatment C on Day 1 of Treatment Period 3, and followed by Treatment D on Day 1 of Treatment Period 4. Each treatment period will be 2 days in duration and there will be a washout period (with no medication) of 10 to 14 days between each treatment period.

Treatment:

Drug: Moxifloxacin

Drug: Placebo

Drug: Canagliflozin (JNJ-28431754)

Sequence 3 (CBDA)

Experimental group

Description:

Each volunteer will receive Treatment C on Day 1 of Treatment Period 1, followed by Treatment B on Day 1 of Treatment Period 2, followed by Treatment D on Day 1 of Treatment Period 3, and followed by Treatment A on Day 1 of Treatment Period 4. Each treatment period will be 2 days in duration and there will be a washout period (with no medication) of 10 to 14 days between each treatment period.

Treatment:

Drug: Moxifloxacin

Drug: Placebo

Drug: Canagliflozin (JNJ-28431754)

Sequence 4 (DCAB)

Experimental group

Description:

Each volunteer will receive Treatment D on Day 1 of Treatment Period 1, followed by Treatment C on Day 1 of Treatment Period 2, followed by Treatment A on Day 1 of Treatment Period 3, and followed by Treatment B on Day 1 of Treatment Period 4. Each treatment period will be 2 days in duration and there will be a washout period (with no medication) of 10 to 14 days between each treatment period.

Treatment:

Drug: Moxifloxacin

Drug: Placebo

Drug: Canagliflozin (JNJ-28431754)