Clinical trial NCT03038711: A Multiple Dose Study to Assess the Safety and Tolerability of BMS-986166 in Healthy Volunteers
Official title: A Randomized, Double Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986166 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-02-01
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: The purpose of this study is to understand if multiple oral doses of BMS-986166 are safe and well tolerated in healthy patients.


Eligibility criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Healthy female patients of non-childbearing potential or male patients as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory evaluations will be eligible to participate in the study
* Body Mass Index (BMI) of 18.0 to 32.0 kg/m2, inclusive
* This study permits the re-enrollment of a patient that has discontinued the study as a pre-treatment failure (i.e. patient has not been randomized / has not been treated). If re-enrolled, the patient must be re-consented

Exclusion Criteria:

* Women who are of childbearing potential, lactating or breastfeeding
* Any significant acute or chronic medical illness judged to be clinically significant by the Investigator and/or Sponsor medical monitor
* Patients with history of any type of heart disease, including ischemia, infarction, clinically significant arrhythmias, sinus syndrome, hypertension, symptomatic orthostatic hypotension, atrioventricular block of any degree, bradycardia, syncope, clinically significant ECG abnormalities, or any congenital heart disease
* Patients with any acute or chronic bacterial, fungal (except history of tinea pedis or ongoing onychomycosis will not be exclusionary) or viral infection within the last 3 months prior to screening, as well as any febrile illness or viral infection within the last 3 months prior to screening, as well as any febrile illness of unknown origin within 14 days of screening
* Patients who have received any live vaccines within 1 month of study drug administration, or who plan to have a live vaccine at any time during the study, including during the follow up period
* Positive test for tuberculosis at screening
* Past or current history of neurologic disorders, Guillain-Barré Syndrome, central or peripheral neuropathies, or past or current symptoms of sustained or recurrent paresthesia's (tingling), numbness, or neuropathic pain (burning, aching or stabbing) in any extremities

Other protocol defined inclusion/exclusion criteria could apply

Primary outcomes:
measure: Incidence of All Adverse Events (AEs)
timeFrame: 77 days
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: 77 days
measure: Severity of all Adverse Events (AEs)
timeFrame: 77 days
measure: Change from baseline in physical examination findings
timeFrame: 77 days
measure: Change from baseline in electrocardiogram (ECG) results
timeFrame: 77 days
measure: Change from baseline in continuous cardiac monitoring data
timeFrame: 15 days
measure: Change from baseline in clinical laboratory test results
timeFrame: 77 days
measure: Change from baseline in body temperature
timeFrame: 77 days
measure: Change from baseline in respiratory rate
timeFrame: 77 days
measure: Change from baseline in seated blood pressure
timeFrame: 77 days
measure: Change from baseline in heart rate
timeFrame: 77 days
Secondary outcomes:
measure: Mean heart rate (HR)
timeFrame: 15 days
measure: Largest decrease in HR from time-matched Day -1 baseline
timeFrame: 15 days
measure: Time to nadir HR from time 0 hour (predose)
timeFrame: 15 days
measure: Time to largest decrease HR from time 0 hour (predose)
timeFrame: 15 days
measure: Mean change from baseline in HR values by timepoint for BMS-986166-treated versus placebo-treated patients where the baseline is defined as time-matched Day -1 HR value
timeFrame: 15 days
measure: Largest percent decrease in absolute lymphocyte count (ALC) from time-matched Day -1 baseline
timeFrame: 35 days
measure: Time to largest percent reduction ALC from time 0 hour (predose)
timeFrame: 35 days
measure: Mean percent change from baseline in ALC values by timepoint for BMS-986166-treated versus placebo-treated patients where the baseline is defined as time-matched Day -1 ALC value
timeFrame: 77 days
measure: Maximum observed blood concentration (Cmax)
timeFrame: 77 days
measure: Time of maximum observed blood concentration (Tmax)
timeFrame: 77 days
measure: Terminal half-life (T-HALF)
timeFrame: 77 days
measure: Area under the blood concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T))
timeFrame: 77 days
measure: Area under the blood concentration-time curve from time zero extrapolated to infinite time (AUC(INF))
timeFrame: 77 days
measure: Apparent total clearance (CLT/F)
timeFrame: 77 days
measure: Apparent steady state volume (Vz/F)
timeFrame: 77 days
measure: Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)]
timeFrame: 77 days
measure: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)]
timeFrame: 77 days
measure: Maximum observed concentration (Cmax)
timeFrame: 77 days
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Development, LLC
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Singhal S, Girgis IG, Xie J, Dutta S, Shevell DE, Throup J. The safety and pharmacokinetics of a novel, selective S1P1R modulator in healthy participants. Expert Opin Investig Drugs. 2020 Apr;29(4):411-422. doi: 10.1080/13543784.2020.1742322.