Clinical trial NCT02211469: A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986104 in Healthy Male Subjects
Official title: A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986104 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2014-08-07
Enrollment: 41
Sex: MALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective in this study is to assess if single doses of BMS-986104 that are safe, tolerable, and result in sufficient lymphopenia (50% to 70% reduction in absolute lymphocyte count) can be achieved without bradycardia or other adverse events in healthy male subjects.


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

Inclusion Criteria:

* Healthy male subjects 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
* Men ages 18 to 49 years, inclusive

Exclusion Criteria:

* Any acute or chronic medical illness judged to be clinically-significant by the Investigator and/or Sponsor medical monitor
* Presence of fecal occult blood at screening
* History of prolonged occupational exposure to organic solvents or pesticides
* History of vitamin B12 deficiency and/or achlorhydria; or a vitamin B12 level at screening \<lower limit of normal (LLN), confirmed by repeat test
* History of Guillain-Barré Syndrome
* Past or current history of central or peripheral neuropathies, or past or current symptoms of sustained or recurrent paresthesias (tingling), numbness, or neuropathic pain (burning, aching or stabbing) in any extremities. Note: Experiencing an extremity "falling asleep" occasionally is not be exclusionary
* Clinically significant abnormality in the neurological exam at baseline (predose)
* Clinically significant nerve electrophysiology abnormalities at baseline (predose)
* Any history of testicular or epididymal disease/disorder
* Clinically significant abnormality on ophthalmologic exam or any findings suggesting an increased risk of macular edema at baseline (predose)
* History of hypothyroidism or carpal tunnel syndrome
* Subjects with history of diabetes mellitus
* Subjects with history of any type of heart disease, including ischemia, infarction, arrhythmias, hypertension, atrioventricular block of any degree, bradycardia, syncope, clinically significant ECG abnormalities, or any congenital heart disease
* Subjects with any acute or chronic bacterial, fungal 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
* Subjects 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
* Positive test for tuberculosis at screening (QuantiFERON® GOLD)

Primary outcomes:
measure: Incidence of all adverse events (AEs) / serious adverse events (SAEs)
timeFrame: Up to 1 month post discharge
measure: Mean difference in ECG heart rate (HR) nadir values
timeFrame: Up to 4 days postdose
measure: Nadir absolute lymphocyte count (ALC) defined as the lowest ALC measured at any time after the dose
timeFrame: Up to 4 days postdose
Secondary outcomes:
measure: Safety and tolerability based on severity, investigator causality assessment and outcomes of all AEs (regardless of seriousness criteria), association between AEs and study drug exposure parameters, and physical examination
timeFrame: Up to 1 month post discharge
measure: Mean difference in ECG HR values in BMS-986104-treated versus placebo-treated healthy male subjects, identifying nadir ECG HR
timeFrame: Day -1 up to 24h and Days 1-5
measure: Percent reduction in ECG HR
timeFrame: Day -1 up to 24h and Days 1-5
measure: Time to nadir ECG HR
timeFrame: Day -1 up to 24h and Days 1-5
measure: Maximum observed blood concentration (Cmax) of BMS-986104
timeFrame: Up to Day 56
measure: Time of maximum observed blood concentration (Tmax) of BMS-986104
timeFrame: Up to Day 56
measure: Terminal half-life (T-HALF) of BMS-986104
timeFrame: Up to Day 56
measure: Area under the blood concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986104
timeFrame: Up to Day 56
measure: Area under the blood concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986104
timeFrame: Up to Day 56
measure: Apparent total clearance (CLT/F) of BMS-986104
timeFrame: Up to Day 56
measure: Apparent volume of distribution of terminal phase (Vz/F) of BMS-986104
timeFrame: Up to Day 56
measure: Metabolite to parent AUC(INF) ratio [MR_AUC(INF)] for both BMS-986104 and BMT-019434
timeFrame: Up to Day 56
measure: Effects of single oral doses of BMS-986104 on the following ALC
timeFrame: Up to 4 days postdose
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Research Unit, Inc.
state: Wisconsin
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: