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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02211469
• Other study ID #: IM001-001
• Status: Completed
• Phase: Phase 1
• First received: August 6, 2014
• Last updated: September 16, 2015
• Start date: August 2014
• Est. completion date: July 2015

Study information

• Verified date: April 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 49 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• BMS-986104

• Placebo

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit, Inc.	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of all adverse events (AEs) / serious adverse events (SAEs)		Up to 1 month post discharge	Yes
Primary	Mean difference in ECG heart rate (HR) nadir values		Up to 4 days postdose	Yes
Primary	Nadir absolute lymphocyte count (ALC) defined as the lowest ALC measured at any time after the dose		Up to 4 days postdose	Yes
Secondary	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		Up to 1 month post discharge	Yes
Secondary	Mean difference in ECG HR values in BMS-986104-treated versus placebo-treated healthy male subjects, identifying nadir ECG HR		Day -1 up to 24h and Days 1-5	Yes
Secondary	Percent reduction in ECG HR		Day -1 up to 24h and Days 1-5	Yes
Secondary	Time to nadir ECG HR		Day -1 up to 24h and Days 1-5	Yes
Secondary	Maximum observed blood concentration (Cmax) of BMS-986104		Up to Day 56	Yes
Secondary	Time of maximum observed blood concentration (Tmax) of BMS-986104		Up to Day 56	Yes
Secondary	Terminal half-life (T-HALF) of BMS-986104		Up to Day 56	Yes
Secondary	Area under the blood concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986104		Up to Day 56	Yes
Secondary	Area under the blood concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986104		Up to Day 56	Yes
Secondary	Apparent total clearance (CLT/F) of BMS-986104		Up to Day 56	Yes
Secondary	Apparent volume of distribution of terminal phase (Vz/F) of BMS-986104		Up to Day 56	Yes
Secondary	Metabolite to parent AUC(INF) ratio [MR_AUC(INF)] for both BMS-986104 and BMT-019434		Up to Day 56	Yes
Secondary	Effects of single oral doses of BMS-986104 on the following ALC	Time to nadir ALC from time 0h (predose); Percent reduction in ALC from baseline to nadir	Up to 4 days postdose	Yes

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
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•   Investigator Inquiry form