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Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-986120 in Healthy Subjects and the Effects of Co-Administration of Midazolam and BMS-986120

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ClinicalTrials.gov Identifier: NCT02208882
Recruitment Status : Completed
First Posted : August 5, 2014
Last Update Posted : July 7, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
The purpose of this study is to assess the safety, tolerability and effect on Midazolam pharmacokinetics of multiple oral doses of BMS-986120 in healthy subjects.

Condition or disease Intervention/treatment Phase
Healthy Adult Volunteers Drug: BMS-986120 Drug: Placebo Drug: Midazolam Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Oral Doses of BMS-986120 in Healthy Subjects and the Effect of BMS-986120 on the Pharmacokinetics of Midazolam in Healthy Subjects
Study Start Date : August 2014
Actual Primary Completion Date : February 2015
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Panel 1: BMS-986120 or Placebo
BMS-986120 or Placebo multiple dose by mouth as specified
Drug: BMS-986120
Drug: Placebo
Experimental: Panel 2: BMS-986120 or Placebo
BMS-986120 or Placebo multiple dose by mouth as specified
Drug: BMS-986120
Drug: Placebo
Experimental: Panel 3: BMS-986120 or Placebo + Midazolam
BMS-986120 or Placebo (multiple dose) + Midazolam (single dose) by mouth as specified
Drug: BMS-986120
Drug: Placebo
Drug: Midazolam
Experimental: Panel 4: BMS-986120 or Placebo
BMS-986120 or Placebo multiple dose by mouth as specified
Drug: BMS-986120
Drug: Placebo



Primary Outcome Measures :
  1. Safety and tolerability measured by number of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters [ Time Frame: Up to 168 days ]
  2. Safety and tolerability measured by percent of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters [ Time Frame: Up to 168 days ]

Secondary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) of BMS-986120, BMT-141464, Midazolam, and 1`hydroxymidazolam [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  2. Time of maximum observed plasma concentration (Tmax) of BMS-986120, BMT-141464, Midazolam, and 1`hydroxymidazolam [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  3. Area under the concentration-time curve from time zero to 24h [AUC(TAU)] of BMS-986120 and BMT-141464 [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  4. Concentration at the end of the dosing Interval (Ctau) of BMS-986120 and BMT-141464 [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  5. Half-life (T-HALF) of BMS-986120 and BMT-141464 [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  6. Apparent total body clearance (CLT/F) of BMS-986120, Midazolam, and 1`hydroxymidazolam [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  7. AUC accumulation index (AI_AUC) of BMS-986120 and BMT-141464 [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  8. Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff_AUC) of BMS-986120 [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  9. Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] of BMT-141464 [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  10. Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) of BMT-141464 [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  11. Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of Midazolam and 1`hydroxymidazolam [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  12. Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of Midazolam and 1`hydroxymidazolam [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  13. Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [MR_AUC(INF)] of 1`hydroxymidazolam [ Time Frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) ]
  14. Change from baseline in protease-activated receptor-4 - agonist peptide (PAR4-AP) induced platelet aggregation of BMS-986120 [ Time Frame: Part A (Days 1-3) & Part B/C (Days 1-19) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  1. Healthy male and female subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
  2. Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI=Weight (kg)/[Height(m)]2
  3. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and men, ages 18 to 75, inclusive

Exclusion Criteria:

  1. Concurrent, or use within 2-weeks of study drug administration, of marketed or investigational, non-steroidal anti-inflammatory compounds (NSAIDS), aspirin or other antiplatelet agents, oral or parenteral anticoagulants
  2. Subjects at screening or prior to first dose with the following abnormal laboratory values upon repeat testing are excluded:

    • i) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >upper limit of normal (ULN)
    • ii) Total bilirubin >ULN, thyroid-stimulating hormone (TSH) >1.5 x ULN with T4 within normal limits (Subjects with mild unconjugated hyperbilirubinemia due to Gilbert's syndrome are excluded)
    • iii) CK >3 x ULN (unless exercise related and CK-MB within normal limits)
    • iv) Activated partial thromboplastin (aPTT) or Prothrombin Time (PT)/International Normalized Ratio (INR) >ULN
    • v) Blood urea nitrogen (BUN) or creatinine (Cr) >ULN
  3. Hemoglobin or hematocrit or platelet count <lower limit of normal (LLN)
  4. Bleeding time exceeding 8 minutes at pre-dose on Day -1
  5. Subjects with micro- or macro-hematuria and/or fecal occult blood detected during screening, baseline or documented during other recent medical assessment, unless deemed not clinically significant by the Investigator and Medical Monitor
  6. Any significant acute or chronic medical illness
  7. Current or recent (within 3 months of study drug administration) gastrointestinal disease
  8. Any major surgery within 12 weeks of study drug administration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02208882


Locations
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United States, Texas
Ppd Development, Lp
Austin, Texas, United States, 78744
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02208882    
Other Study ID Numbers: CV004-006
First Posted: August 5, 2014    Key Record Dates
Last Update Posted: July 7, 2015
Last Verified: July 2015
Additional relevant MeSH terms:
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Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action