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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 主要终点
- Change from baseline in mean 24-hour plasma glucose concentrations
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Canagliflozin (JNJ-28431754) (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Canagliflozin (JNJ-28431754) (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Canagliflozin (JNJ-28431754) (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Canagliflozin (JNJ-28431754) (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Canagliflozin (JNJ-28431754) (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in mean 24-hour plasma glucose concentrations
时间窗: 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).
Visual analog scale (VAS) scores related to hunger, satiety, fullness and prospective food consumption
时间窗: 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).
Change from baseline in urine glucose excretion per day
时间窗: 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).
Change from baseline in urine glucose excretion per hour
时间窗: 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).
次要结局
- Change from baseline in insulin excursions (after breakfast)(Day -1 (Baseline) up to Day 14)
- Change from baseline in mean 24-hour plasma insulin concentrations(Day -1 (Baseline) up to Day 14)
- Change from baseline in mean 24-hour plasma C-peptide concentrations(Day -1 (Baseline) up to Day 14)
- Renal threshold for glucose excretion(Up to Day 17)
- Change from baseline in glucose excursions (after breakfast)(Day -1 (Baseline) up to Day 14)
- Change from baseline in beta cell function(Day -1 (Baseline) up to Day 14)