Clinical trial NCT01756404: Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of Canagliflozin (JNJ-28431754) in Otherwise Healthy Obese Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Canagliflozin (JNJ-28431754)
Pharmacokinetics
Pharmacodynamics
Obesity
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2012-12-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in urine glucose excretion per day
timeFrame: Day -1 (Baseline) up to Day 17
measure: Change from baseline in urine glucose excretion per hour
timeFrame: Day -1 (Baseline) up to Day 17
measure: Visual analog scale (VAS) scores related to hunger, satiety, fullness and prospective food consumption
timeFrame: Day -2 up to Day 17
measure: Change from baseline in mean 24-hour plasma glucose concentrations
timeFrame: Day -1 (Baseline) up to Day 16
Secondary outcomes:
measure: Renal threshold for glucose excretion
timeFrame: Up to Day 17
measure: Change from baseline in mean 24-hour plasma insulin concentrations
timeFrame: Day -1 (Baseline) up to Day 14
measure: Change from baseline in mean 24-hour plasma C-peptide concentrations
timeFrame: Day -1 (Baseline) up to Day 14
measure: Change from baseline in glucose excursions (after breakfast)
timeFrame: Day -1 (Baseline) up to Day 14
measure: Change from baseline in insulin excursions (after breakfast)
timeFrame: Day -1 (Baseline) up to Day 14
measure: Change from baseline in beta cell function
timeFrame: Day -1 (Baseline) up to Day 14
Other outcomes:
Locations:
city: Miramar
country: United States
state: Florida
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References: