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

A Randomized, Double-Blind, Double-Dummy, Placebo- and Positive-Controlled, Four-Way Crossover Study Evaluating ECG Intervals in Healthy Adults Receiving a Single, Oral Dose of JNJ-28431754 at Therapeutic and Supra-Therapeutic Doses

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Canagliflozin (JNJ-28431754); Drug: Placebo; Drug: Moxifloxacin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1 (ADBC); 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.	Drug: Canagliflozin (JNJ-28431754); One 300 mg dose of canagliflozin (JNJ-28431754) (comprising one 100 mg over-encapsulated tablet and one 200 mg over-encapsulated tablet) taken orally (by mouth) on Day 1 of Treatment A. One 1,200 mg dose of canagliflozin (comprising six 200 mg over-encapsulated tablets) taken orally on Day 1 of Treatment B.; Other Names: JNJ-28431754; Drug: Placebo; Four over-encapsulated matching placebo tablets taken orally (by mouth) on Day 1 of Treatment A. Six over-encapsulated matching placebo tablets taken orally on Day 1 of Treatment C. Five encapsulated matching placebo tablets taken orally on Day 1 of Treatment D.; Drug: Moxifloxacin; One 400 mg over-encapsulated tablet of moxifloxacin taken orally (by mouth) on Day 1 of Treatment D.
Experimental: Sequence 2 (BACD); 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.	Drug: Canagliflozin (JNJ-28431754); One 300 mg dose of canagliflozin (JNJ-28431754) (comprising one 100 mg over-encapsulated tablet and one 200 mg over-encapsulated tablet) taken orally (by mouth) on Day 1 of Treatment A. One 1,200 mg dose of canagliflozin (comprising six 200 mg over-encapsulated tablets) taken orally on Day 1 of Treatment B.; Other Names: JNJ-28431754; Drug: Placebo; Four over-encapsulated matching placebo tablets taken orally (by mouth) on Day 1 of Treatment A. Six over-encapsulated matching placebo tablets taken orally on Day 1 of Treatment C. Five encapsulated matching placebo tablets taken orally on Day 1 of Treatment D.; Drug: Moxifloxacin; One 400 mg over-encapsulated tablet of moxifloxacin taken orally (by mouth) on Day 1 of Treatment D.
Experimental: Sequence 3 (CBDA); 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.	Drug: Canagliflozin (JNJ-28431754); One 300 mg dose of canagliflozin (JNJ-28431754) (comprising one 100 mg over-encapsulated tablet and one 200 mg over-encapsulated tablet) taken orally (by mouth) on Day 1 of Treatment A. One 1,200 mg dose of canagliflozin (comprising six 200 mg over-encapsulated tablets) taken orally on Day 1 of Treatment B.; Other Names: JNJ-28431754; Drug: Placebo; Four over-encapsulated matching placebo tablets taken orally (by mouth) on Day 1 of Treatment A. Six over-encapsulated matching placebo tablets taken orally on Day 1 of Treatment C. Five encapsulated matching placebo tablets taken orally on Day 1 of Treatment D.; Drug: Moxifloxacin; One 400 mg over-encapsulated tablet of moxifloxacin taken orally (by mouth) on Day 1 of Treatment D.
Experimental: Sequence 4 (DCAB); 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.	Drug: Canagliflozin (JNJ-28431754); One 300 mg dose of canagliflozin (JNJ-28431754) (comprising one 100 mg over-encapsulated tablet and one 200 mg over-encapsulated tablet) taken orally (by mouth) on Day 1 of Treatment A. One 1,200 mg dose of canagliflozin (comprising six 200 mg over-encapsulated tablets) taken orally on Day 1 of Treatment B.; Other Names: JNJ-28431754; Drug: Placebo; Four over-encapsulated matching placebo tablets taken orally (by mouth) on Day 1 of Treatment A. Six over-encapsulated matching placebo tablets taken orally on Day 1 of Treatment C. Five encapsulated matching placebo tablets taken orally on Day 1 of Treatment D.; Drug: Moxifloxacin; One 400 mg over-encapsulated tablet of moxifloxacin taken orally (by mouth) on Day 1 of Treatment D.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in QTc intervals	QT intervals (assessment of the electrical activity of the heart) will be measured from 12-lead electrocardiogram (ECG) readings and will be corrected for heart rate. The corrected QT intervals (QTc) obtained following single doses of 300 mg canagliflozin (JNJ-28431754), 1,200 mg canagliflozin, and 400 mg moxifloxacin, will be compared with QTc intervals obtained following dosing with placebo.	Day 1 (Predose) up to Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of volunteers with adverse events	Adverse events will be used as a measure of safety and tolerability.	Up to 61 days
Plasma concentrations of canagliflozin (JNJ-28431754)	Plasma concentrations of canagliflozin (JNJ-28431754), following the administration of a single 300 mg dose and a single 1,200 mg dose, will be used to determine pharmacokinetic parameters for canagliflozin (measurements describing how the body affects the drug).	Up to Day 2
QRS intervals obtained from 12-lead electrocardiogram (ECG) readings	QRS intervals will be obtained from 12-lead electrocardiogram (ECG) readings following a single 300 mg dose and a single 1,200 mg dose of canagliflozin (JNJ-28431754).	Up to Day 2
PR intervals obtained from 12-lead electrocardiogram (ECG) readings	PR intervals will be obtained from 12-lead electrocardiogram (ECG) readings following a single 300 mg dose and a single 1,200 mg dose of canagliflozin (JNJ-28431754).	Up to Day 2

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

Helpful Links

• A Randomized, Double-Blind, Double-Dummy, Placebo- and Positive-Controlled, Four-Way Crossover Study Evaluating Electrocardiogram Intervals in Healthy Adults Receiving a Single, Oral Dose of JNJ-28431754 at Therapeutic and Supra-Therapeutic Doses

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: February 6, 2013
• First Submitted That Met QC Criteria: February 6, 2013
• First Posted (Estimate): February 8, 2013

Study Record Updates

• Last Update Posted (Estimate): June 29, 2016
• Last Update Submitted That Met QC Criteria: June 28, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Moxifloxacin; Canagliflozin (JNJ-28431754); QT/QTc Interval; Electrocardiogram Parameters; Therapeutic dose; Supra-Therapeutic dose
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Sodium-Glucose Transporter 2 Inhibitors; Moxifloxacin; Canagliflozin
• Other Study ID Numbers: CR015514; 28431754DIA1010 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)