A Multiple Dose Study to Assess the Safety and Tolerability of BMS-986166 in Healthy Volunteers

A Randomized, Double Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986166 in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: BMS-986166; Other: Placebo matching BMS-986166

• Study Type: Interventional
• Enrollment (Actual): 213
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Ppd Development, Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SCREENING
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dose Panel 1; BMS-986166 or Placebo matching BMS-986166	Drug: BMS-986166; Specified dose on specified days; Other: Placebo matching BMS-986166; Specified dose on specified days
EXPERIMENTAL: Dose Panel 2; BMS-986166 or Placebo matching BMS-986166	Drug: BMS-986166; Specified dose on specified days; Other: Placebo matching BMS-986166; Specified dose on specified days
EXPERIMENTAL: Dose Panel 3; BMS-986166 or Placebo matching BMS-986166	Drug: BMS-986166; Specified dose on specified days; Other: Placebo matching BMS-986166; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of All Adverse Events (AEs)	measured by number of patients	77 days
Incidence of Serious Adverse Events (SAEs)	measured by number of patients	77 days
Severity of all Adverse Events (AEs)	measured by investigator	77 days
Change from baseline in physical examination findings	measured by investigator	77 days
Change from baseline in electrocardiogram (ECG) results	measured by ECG	77 days
Change from baseline in continuous cardiac monitoring data	measured with external monitoring device	15 days
Change from baseline in clinical laboratory test results	measured by serum chemistry, hematology, serology and urinalysis results	77 days
Change from baseline in body temperature	measured in degrees Celsius or Fahrenheit	77 days
Change from baseline in respiratory rate	measured by investigator	77 days
Change from baseline in seated blood pressure	measured by investigator	77 days
Change from baseline in heart rate	measured by investigator	77 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean heart rate (HR)	Calculated from nadir HR to time-matched HR on Day -1	15 days
Largest decrease in HR from time-matched Day -1 baseline	measured by investigator	15 days
Time to nadir HR from time 0 hour (predose)	measured by investigator	15 days
Time to largest decrease HR from time 0 hour (predose)	measured by investigator	15 days
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	measured by investigator	15 days
Largest percent decrease in absolute lymphocyte count (ALC) from time-matched Day -1 baseline	measured by ALC	35 days
Time to largest percent reduction ALC from time 0 hour (predose)	measured by ALC	35 days
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	measured by ALC	77 days
Maximum observed blood concentration (Cmax)	measured by blood concentration versus time data	77 days
Time of maximum observed blood concentration (Tmax)	measured by blood concentration versus time data	77 days
Terminal half-life (T-HALF)	measured by blood concentration versus time data	77 days
Area under the blood concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T))	measured by blood concentration versus time data	77 days
Area under the blood concentration-time curve from time zero extrapolated to infinite time (AUC(INF))	measured by blood concentration versus time data	77 days
Apparent total clearance (CLT/F)	measured by blood concentration versus time data	77 days
Apparent steady state volume (Vz/F)	measured by blood concentration versus time data	77 days
Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)]	Used to calculate metabolite to parent molar ratio of pharmacokinetic parameter	77 days
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)]	Used to calculate metabolite to parent molar ratio of pharmacokinetic parameter	77 days
Maximum observed concentration (Cmax)	Used to calculate metabolite to parent molar ratio of pharmacokinetic parameter	77 days

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2017
• Primary Completion (ACTUAL): August 10, 2017
• Study Completion (ACTUAL): August 10, 2017

Study Registration Dates

• First Submitted: January 26, 2017
• First Submitted That Met QC Criteria: January 30, 2017
• First Posted (ESTIMATE): February 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 28, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: IM018-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No