Placebo-Controlled, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 115
- 试验地点
- 1
- 主要终点
- Safety and tolerability of multiple oral doses of BMS-933043 in healthy subjects measured by AEs, Vital signs, clinical laboratory test results, physical examination findings, neurological examination findings and electrocardiogram (ECG) parameters
研究概览
简要总结
Includes a placebo-controlled sequential, ascending multiple-dose panels (10 panels, 8 ascending doses, and 2 fixed Japanese Panels exploring safety, tolerability, and Pharmacokinetic (PK) measures
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects as determined by no clinically significant deviation from normal medical history, physical examination, ECGs and clinical laboratory determinations
- •Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2
- •Normal Neurological Exam (LP subjects only: to rule out focal CNS lesions that would render LP unsafe)
- •Men and women, ages 18 to 55 years, inclusive.
- •Women who are not of childbearing potential (WOCBP) [ie, who are postmenopausal or surgically sterile] and men
- •Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
- •Women must not be breastfeeding
- •Sexually active fertile men must use effective birth control if their partners are WOCBP throughout the study and for 90 days after last dose
排除标准
- •Any significant acute or chronic medical illness
- •Current or recent (within 3 months of study drug administration) gastrointestinal disease
- •Any major surgery within 4 weeks of study drug administration
- •Any gastrointestinal surgery that could impact upon the absorption of study drug
- •Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration
- •Blood transfusion within 4 weeks of study drug administration
- •Inability to tolerate oral medication
- •Inability to be venipunctured and/or tolerate venous access
- •Smoking more than 1 cigarette/cigar per week, within 3 months prior to screening
- •Regular daily use of nicotine products or Varenicline (Chantix® or Champix®) within 3 months prior to screening
- •Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders (4th Edition) [DSM IV], Diagnostic Criteria for Drug and Alcohol Abuse
- •History of cardiac arrhythmias, or palpitations associated with presyncope or syncope or history of unexplained syncope
研究组 & 干预措施
Panel 1:BMS-933043(2mg)/Placebo+Antacid Buffer Solution
BMS-933043 2 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
Panel 1:BMS-933043(2mg)/Placebo+Antacid Buffer Solution
BMS-933043 2 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 1:BMS-933043(2mg)/Placebo+Antacid Buffer Solution
BMS-933043 2 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
Panel 2:BMS-933043(5mg)/Placebo+Antacid Buffer Solution
BMS-933043 5 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
Panel 2:BMS-933043(5mg)/Placebo+Antacid Buffer Solution
BMS-933043 5 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 2:BMS-933043(5mg)/Placebo+Antacid Buffer Solution
BMS-933043 5 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
Panel 3:BMS-933043(10mg)/Placebo+Antacid Buffer Solution
BMS-933043 10 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
Panel 3:BMS-933043(10mg)/Placebo+Antacid Buffer Solution
BMS-933043 10 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 3:BMS-933043(10mg)/Placebo+Antacid Buffer Solution
BMS-933043 10 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
Panel 4:BMS-933043(25mg)/Placebo+Antacid Buffer Solution
BMS-933043 25 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
Panel 4:BMS-933043(25mg)/Placebo+Antacid Buffer Solution
BMS-933043 25 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 4:BMS-933043(25mg)/Placebo+Antacid Buffer Solution
BMS-933043 25 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
Panel 5:BMS-933043(50mg)/Placebo+Antacid Buffer Solution
BMS-933043 50 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
CSF sampling required
干预措施: BMS-933043 (Drug)
Panel 8:BMS-933043(25mg)/Placebo+Antacid Buffer Predose
MAD Phase: Japanese Subjects. Cerebrospinal fluid (CSF) sampling not required
BMS-933043 25 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
Panel 5:BMS-933043(50mg)/Placebo+Antacid Buffer Solution
BMS-933043 50 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
CSF sampling required
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 5:BMS-933043(50mg)/Placebo+Antacid Buffer Solution
BMS-933043 50 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
CSF sampling required
干预措施: Antacid Buffer Predose Solution (Drug)
Panel 6:BMS-933043(100mg)/Placebo+Antacid Buffer Solution
BMS-933043 100 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
Panel 6:BMS-933043(100mg)/Placebo+Antacid Buffer Solution
BMS-933043 100 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 6:BMS-933043(100mg)/Placebo+Antacid Buffer Solution
BMS-933043 100 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
Panel 7:BMS-933043(200mg)/Placebo+Antacid Buffer Solution
BMS-933043 200 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
Panel 7:BMS-933043(200mg)/Placebo+Antacid Buffer Solution
BMS-933043 200 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 7:BMS-933043(200mg)/Placebo+Antacid Buffer Solution
BMS-933043 200 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
Panel 8:BMS-933043(25mg)/Placebo+Antacid Buffer Predose
MAD Phase: Japanese Subjects. Cerebrospinal fluid (CSF) sampling not required
BMS-933043 25 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 8:BMS-933043(25mg)/Placebo+Antacid Buffer Predose
MAD Phase: Japanese Subjects. Cerebrospinal fluid (CSF) sampling not required
BMS-933043 25 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
Panel 9:BMS-933043(200mg)/Placebo+Antacid Buffer Predose
Japanese Subjects. CSF sampling not required.
BMS-933043 200 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
Panel 9:BMS-933043(200mg)/Placebo+Antacid Buffer Predose
Japanese Subjects. CSF sampling not required.
BMS-933043 200 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 9:BMS-933043(200mg)/Placebo+Antacid Buffer Predose
Japanese Subjects. CSF sampling not required.
BMS-933043 200 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
Panel 10:BMS-933043(350mg)/Placebo+Antacid Buffer Predose
BMS-933043 350 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
Panel 10:BMS-933043(350mg)/Placebo+Antacid Buffer Predose
BMS-933043 350 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
Panel 10:BMS-933043(350mg)/Placebo+Antacid Buffer Predose
BMS-933043 350 mg solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
CSF Panel:BMS-933043(MTD)/Placebo+Antacid Buffer Predose
If Panel 5 does not run. CSF Sampling at steady state
BMS-933043 maximum tolerated dose (MTD), solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: BMS-933043 (Drug)
CSF Panel:BMS-933043(MTD)/Placebo+Antacid Buffer Predose
If Panel 5 does not run. CSF Sampling at steady state
BMS-933043 maximum tolerated dose (MTD), solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Placebo matching with BMS-933043 (Drug)
CSF Panel:BMS-933043(MTD)/Placebo+Antacid Buffer Predose
If Panel 5 does not run. CSF Sampling at steady state
BMS-933043 maximum tolerated dose (MTD), solution by mouth twice daily for 10 days
OR
Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days
Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days
干预措施: Antacid Buffer Predose Solution (Drug)
结局指标
主要结局
Safety and tolerability of multiple oral doses of BMS-933043 in healthy subjects measured by AEs, Vital signs, clinical laboratory test results, physical examination findings, neurological examination findings and electrocardiogram (ECG) parameters
时间窗: Up to Day 26 of Follow-up
AEs = Adverse Events
次要结局
- Area under the concentration-time curve in one dosing interval [AUC(TAU)](Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)
- Maximum observed plasma concentration (Cmax)(Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)
- Time of maximum observed plasma concentration (Tmax)(Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)
- Plasma half-life (T-HALF)(Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)
- Trough observed plasma concentration (Cmin) between dose interval(Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)
- Volume of distribution at steady-state (VSS/F) of BMS-933043(Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)
- Accumulation index (AI): ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose(Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)
- Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR AUC(tau)](Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)
- Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight [MR Cmax](Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)
- CSF penetration of BMS-933043(Day 8)
- Effect of BMS-933043 on ECG intervals and to explore the relationship between plasma exposure and ECG intervals(Baseline (Day -2), Day 1, Day 6 and Day 10)
- Safety and tolerability of multiple oral doses of BMS-9333043 in Japanese healthy subjects is measured by AEs, Vital signs, clinical laboratory test results, physical examination findings, neurological examination findings and ECG parameters(Up to 6 months)
- Effect of ethnicity (Japanese versus non-Japanese) on PK of BMS-933043 will be assessed graphically and by point estimates and 90% confidence intervals for geometric mean ratio for Cmax using data from subjects receiving the same dose of BMS-933043(Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12)