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

• Register: ClinicalTrials.gov
• Last refreshed on: 28 September 2015
• Main ID: NCT02211469
• Date of registration: 06/08/2014
• Prospective Registration: No
• Primary sponsor: Bristol-Myers Squibb
• Public 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
• Scientific 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
• Date of first enrolment: August 2014
• Target sample size: 41
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02211469
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion 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
- 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)



Age minimum: 18 Years
Age maximum: 49 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: BMS-986104

Drug: Placebo

Primary Outcome(s)

Incidence of all adverse events (AEs) / serious adverse events (SAEs) [Time Frame: Up to 1 month post discharge]

Nadir absolute lymphocyte count (ALC) defined as the lowest ALC measured at any time after the dose [Time Frame: Up to 4 days postdose]

Mean difference in ECG heart rate (HR) nadir values [Time Frame: Up to 4 days postdose]

Secondary Outcome(s)

Percent reduction in ECG HR [Time Frame: Day -1 up to 24h and Days 1-5]

Apparent volume of distribution of terminal phase (Vz/F) of BMS-986104 [Time Frame: Up to Day 56]

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 [Time Frame: Up to 1 month post discharge]

Apparent total clearance (CLT/F) of BMS-986104 [Time Frame: Up to Day 56]

Area under the blood concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986104 [Time Frame: Up to Day 56]

Time of maximum observed blood concentration (Tmax) of BMS-986104 [Time Frame: Up to Day 56]

Terminal half-life (T-HALF) of BMS-986104 [Time Frame: Up to Day 56]

Area under the blood concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986104 [Time Frame: Up to Day 56]

Effects of single oral doses of BMS-986104 on the following ALC [Time Frame: Up to 4 days postdose]

Maximum observed blood concentration (Cmax) of BMS-986104 [Time Frame: Up to Day 56]

Mean difference in ECG HR values in BMS-986104-treated versus placebo-treated healthy male subjects, identifying nadir ECG HR [Time Frame: Day -1 up to 24h and Days 1-5]

Time to nadir ECG HR [Time Frame: Day -1 up to 24h and Days 1-5]

Metabolite to parent AUC(INF) ratio [MR_AUC(INF)] for both BMS-986104 and BMT-019434 [Time Frame: Up to Day 56]

Secondary ID(s)

IM001-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors