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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT01787357
First received: February 6, 2013
Last updated: March 11, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Canagliflozin (JNJ-28431754)
Drug: Placebo
Drug: Moxifloxacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Change from baseline in QTc intervals [ Time Frame: Day 1 (Predose) up to Day 2 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of volunteers with adverse events [ Time Frame: Up to 61 days ] [ Designated as safety issue: No ]
    Adverse events will be used as a measure of safety and tolerability.

  • Plasma concentrations of canagliflozin (JNJ-28431754) [ Time Frame: Up to Day 2 ] [ Designated as safety issue: No ]
    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).

  • QRS intervals obtained from 12-lead electrocardiogram (ECG) readings [ Time Frame: Up to Day 2 ] [ Designated as safety issue: No ]
    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).

  • PR intervals obtained from 12-lead electrocardiogram (ECG) readings [ Time Frame: Up to Day 2 ] [ Designated as safety issue: No ]
    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).


Enrollment: 60
Study Start Date: June 2008
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01787357

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT01787357     History of Changes
Other Study ID Numbers: CR015514, 28431754DIA1010
Study First Received: February 6, 2013
Last Updated: March 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Healthy
Canagliflozin (JNJ-28431754)
Pharmacokinetics
Moxifloxacin
Electrocardiogram Parameters
QT/QTc Interval
Therapeutic dose
Supra-Therapeutic dose

Additional relevant MeSH terms:
Moxifloxacin
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Anti-Infective Agents
Antineoplastic Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Combined
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Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
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Therapeutic Uses
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Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014