Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of Canagliflozin (JNJ-28431754) in Otherwise Healthy Obese Volunteers

December 11, 2018 updated by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

A Double-Blind, Randomized, Placebo-Controlled, Sequential Cohort Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of JNJ-28431754 in Otherwise Healthy Obese Male and Female Subjects

The purpose of this study is to assess the pharmacokinetics (ie, how the body affects the drug) and pharmacodynamics (ie, how the drug affects the body) of increasing doses of canagliflozin (JNJ-28431754) in healthy obese volunteers.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study will be a single-center, randomized (the treatment is assigned by chance), double-blind (neither investigator nor volunteer knows the identity of the assigned treatment), placebo-controlled (one of the study medications is inactive), ascending multiple dose study (increasing doses of study medication) to assess the pharmacokinetics and pharmacodynamics of canagliflozin (a drug currently being investigated for the treatment of type 2 diabetes mellitus) in otherwise healthy obese 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 5 cohorts (groups) made up of 16 otherwise healthy obese men and women. Within each group, 12 volunteers will be given canagliflozin once or twice daily and 4 volunteers will be given placebo (inactive medication) once or twice daily for 14 days. The dose of canagliflozin will be different for each of the 5 groups and the second group will not begin treatment until at least 21 days after the first group start treatment. This 21-day gap will be applied to all subsequent groups. Each volunteer will participate in the study for approximately 58 days.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Volunteers must have a body mass index (BMI = weight in kg/height in m2) of 30.0 to 39.9 kg/m2
  • Volunteers must be non-diabetic as confirmed by fasting plasma glucose <126 mg/dL
  • Volunteers must be non-smoker or non-tobacco users (not smoked cigarettes or used tobacco-containing products for 3 months prior to screening)

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 having taken anti-obesity medications (prescription or non-prescription) within 3 months of the screening visit, or anticipates a need to take any of these drugs during the course of the study
  • History of gastric banding, gastric bypass or other gastric-reduction surgery
  • History of eating disorder or recent significant changes in body weight due to dieting or nutritional treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
Each volunteer will receive a total daily dose of 30 mg of canagliflozin (JNJ-28431754) or placebo (inactive medication) on Days 1 through 14.
Drug: Canagliflozin (JNJ-28431754)
A 30mg/day, 100 mg/day, 300 mg/day, or 600 mg/day liquid dose administered once daily; a 300mg/day liquid dose administered in 2 divided doses (2x150 mg); or a 600 mg/day liquid dose administered in 2 divided doses (2x300 mg) using an oral (by mouth) liquid dispenser on Days 1 through 14.
Other Names:
  • JNJ-28431754
Drug: Placebo
Matching placebo (inactive medication) liquid dose(s) administered using an oral liquid dispenser once or twice daily on Days 1 through 14.
Experimental: Cohort 2
Each volunteer will receive a total daily dose of 100 mg of canagliflozin (JNJ-28431754) or placebo (inactive medication) on Days 1 through 14.
Drug: Canagliflozin (JNJ-28431754)
A 30mg/day, 100 mg/day, 300 mg/day, or 600 mg/day liquid dose administered once daily; a 300mg/day liquid dose administered in 2 divided doses (2x150 mg); or a 600 mg/day liquid dose administered in 2 divided doses (2x300 mg) using an oral (by mouth) liquid dispenser on Days 1 through 14.
Other Names:
  • JNJ-28431754
Drug: Placebo
Matching placebo (inactive medication) liquid dose(s) administered using an oral liquid dispenser once or twice daily on Days 1 through 14.
Experimental: Cohort 3
Each volunteer will receive a total daily dose of 300 mg of canagliflozin (JNJ-28431754) or placebo (inactive medication) on Days 1 through 14.
Drug: Canagliflozin (JNJ-28431754)
A 30mg/day, 100 mg/day, 300 mg/day, or 600 mg/day liquid dose administered once daily; a 300mg/day liquid dose administered in 2 divided doses (2x150 mg); or a 600 mg/day liquid dose administered in 2 divided doses (2x300 mg) using an oral (by mouth) liquid dispenser on Days 1 through 14.
Other Names:
  • JNJ-28431754
Drug: Placebo
Matching placebo (inactive medication) liquid dose(s) administered using an oral liquid dispenser once or twice daily on Days 1 through 14.
Experimental: Cohort 4
Each volunteer will receive a total daily dose of 600 mg of canagliflozin (JNJ-28431754) or placebo (inactive medication) on Days 1 through 14.
Drug: Canagliflozin (JNJ-28431754)
A 30mg/day, 100 mg/day, 300 mg/day, or 600 mg/day liquid dose administered once daily; a 300mg/day liquid dose administered in 2 divided doses (2x150 mg); or a 600 mg/day liquid dose administered in 2 divided doses (2x300 mg) using an oral (by mouth) liquid dispenser on Days 1 through 14.
Other Names:
  • JNJ-28431754
Drug: Placebo
Matching placebo (inactive medication) liquid dose(s) administered using an oral liquid dispenser once or twice daily on Days 1 through 14.
Experimental: Cohort 5
Each volunteer will receive 300 mg of canagliflozin (JNJ-28431754) twice daily (600 mg total daily dose) or placebo (inactive medication) twice daily on Days 1 through 14.
Drug: Canagliflozin (JNJ-28431754)
A 30mg/day, 100 mg/day, 300 mg/day, or 600 mg/day liquid dose administered once daily; a 300mg/day liquid dose administered in 2 divided doses (2x150 mg); or a 600 mg/day liquid dose administered in 2 divided doses (2x300 mg) using an oral (by mouth) liquid dispenser on Days 1 through 14.
Other Names:
  • JNJ-28431754
Drug: Placebo
Matching placebo (inactive medication) liquid dose(s) administered using an oral liquid dispenser once or twice daily on Days 1 through 14.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from baseline in urine glucose excretion per day
Time Frame: Day -1 (Baseline) up to Day 17
The change from baseline in urine excretion per day will be compared following escalating doses of canagliflozin (JNJ-28431754).
Day -1 (Baseline) up to Day 17
Change from baseline in urine glucose excretion per hour
Time Frame: Day -1 (Baseline) up to Day 17
The change from baseline in urine excretion per hour will be compared following escalating doses of canagliflozin (JNJ-28431754).
Day -1 (Baseline) up to Day 17
Visual analog scale (VAS) scores related to hunger, satiety, fullness and prospective food consumption
Time Frame: Day -2 up to Day 17
Visual analog scale (VAS) scores will be obtained from the VAS questionnaire. In the VAS questionnaire, volunteers mark a point on a line (drawn between 2 statements) to indicate how they feel about the statements. The statements about hunger are as follows: "I am not hungry at all" and "I have never been hungrier". Other statements relate to satiety (feeling satisfied), feeling full and prospective food consumption. Scores will be compared following escalating doses of canagliflozin (JNJ-28431754).
Day -2 up to Day 17
Change from baseline in mean 24-hour plasma glucose concentrations
Time Frame: Day -1 (Baseline) up to Day 16
The change from baseline in mean 24-hour plasma glucose concentrations will be compared following escalating doses of canagliflozin (JNJ-28431754).
Day -1 (Baseline) up to Day 16

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Renal threshold for glucose excretion
Time Frame: Up to Day 17
The point at which glucose starts to appear in the urine is known as the renal threshold. The way in which the renal threshold varies in relation to the dose of canagliflozin (JNJ-28431754) will be calculated.
Up to Day 17
Change from baseline in mean 24-hour plasma insulin concentrations
Time Frame: Day -1 (Baseline) up to Day 14
The change from baseline in mean 24-hour plasma insulin concentrations will be compared following escalating doses of canagliflozin (JNJ-28431754).
Day -1 (Baseline) up to Day 14
Change from baseline in mean 24-hour plasma C-peptide concentrations
Time Frame: Day -1 (Baseline) up to Day 14
The change from baseline in mean 24-hour plasma C-peptide concentrations will be compared following escalating doses of canagliflozin (JNJ-28431754).
Day -1 (Baseline) up to Day 14
Change from baseline in glucose excursions (after breakfast)
Time Frame: Day -1 (Baseline) up to Day 14
Defined as the difference between the maximum glucose values observed during the 4-hour post-meal period minus the mean of the premeal measurements. Results will be compared following escalating doses of canagliflozin (JNJ-28431754).
Day -1 (Baseline) up to Day 14
Change from baseline in insulin excursions (after breakfast)
Time Frame: Day -1 (Baseline) up to Day 14
Defined as the difference between the maximum insulin values observed during the 4-hour post-meal period minus the mean of the premeal measurements. Results will be compared following escalating doses of canagliflozin (JNJ-28431754).
Day -1 (Baseline) up to Day 14
Change from baseline in beta cell function
Time Frame: Day -1 (Baseline) up to Day 14
Beta cell function will be calculated from the glucose, insulin, and C-peptide measurements taken post-breakfast on Day -1 up to Day 14. Results will be compared following escalating doses of canagliflozin (JNJ-28431754).
Day -1 (Baseline) up to Day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 14, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 5, 2007

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 5, 2007

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 20, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 25, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 13, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR013765
  • 28431754NAP1008 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

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