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Completed

NCT Number: NCT01605994

Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043 in Healthy Subjects

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

Completed

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Key information

Conditions

Healthy Adult Normals

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinilabs, Inc.

New York, 10019, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BMS-933043

Drug

Placebo matching with BMS-933043

Drug

Antacid Buffer Predose Solution

Drug

Primary outcomes

  1. 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

    Time frame: Up to Day 26 of Follow-up

    AEs = Adverse Events

Secondary outcomes

  1. Maximum observed plasma concentration (Cmax)

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

    PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data

  2. Time of maximum observed plasma concentration (Tmax)

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

    PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data

  3. Area under the concentration-time curve in one dosing interval [AUC(TAU)]

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

    PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data

  4. Plasma half-life (T-HALF)

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

    PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data

  5. Trough observed plasma concentration (Cmin) between dose interval

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

    PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data

  6. Volume of distribution at steady-state (VSS/F) of BMS-933043

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

    PK of BMS-933043 will be derived from plasma concentration versus time and urinary excretion data

  7. Accumulation index (AI): ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

    PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data

  8. Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR AUC(tau)]

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

    PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data

  9. Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight [MR Cmax]

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

    PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data

  10. CSF penetration of BMS-933043

    Time frame: Day 8

    Cerebral Spinal Fluid (CSF) will be analyzed for drug levels to confirm adequate central nervous system (CNS) penetration (>2 nM is required) and to estimate the brain/plasma ratio in humans

  11. Effect of BMS-933043 on ECG intervals and to explore the relationship between plasma exposure and ECG intervals

    Time frame: Baseline (Day -2), Day 1, Day 6 and Day 10

    The effects of BMS-933043 on ECG parameters (heart rate, QTcF, PR, and QRS) will be explored graphically and by summary statistics. Absolute levels, as well as changes from baseline, will be summarized and plotted versus time by treatment and day for each ECG parameter. Frequency distributions for subjects' maximum values will be provided by treatment. The relationships between ECG parameters and BMS-933043 concentrations may be explored using scatter plots and the relationship between the change from baseline in QTcF and the BMS-933043 concentration may be estimated

  12. 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

    Time frame: Up to 6 months

  13. 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

    Time frame: Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study title

Placebo-Controlled, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-933043

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
May 25, 2012
Registry last updated
Jun 27, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.