Clinical trial NCT01605994: Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043 in Healthy Subjects
Official title: Placebo-Controlled, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adult Normals
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-05-25
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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
timeFrame: Up to Day 26 of Follow-up
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
measure: Time of maximum observed plasma concentration (Tmax)
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
measure: Area under the concentration-time curve in one dosing interval [AUC(TAU)]
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
measure: Plasma half-life (T-HALF)
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
measure: Trough observed plasma concentration (Cmin) between dose interval
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
measure: Volume of distribution at steady-state (VSS/F) of BMS-933043
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
measure: Accumulation index (AI): ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
measure: Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR AUC(tau)]
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
measure: Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight [MR Cmax]
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
measure: CSF penetration of BMS-933043
timeFrame: Day 8
measure: Effect of BMS-933043 on ECG intervals and to explore the relationship between plasma exposure and ECG intervals
timeFrame: Baseline (Day -2), Day 1, Day 6 and Day 10
measure: 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
timeFrame: Up to 6 months
measure: 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
timeFrame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12
Other outcomes:
Locations:
city: New York
country: United States
facility: Clinilabs, Inc.
state: New York
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: