Back to resultsA Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986104 in Healthy Male Subjects
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BMS-986104
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
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)
Sites / Locations
- Covance Clinical Research Unit, Inc.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Panel 1: BMS-986104 or Placebo
Panel 2: BMS-986104 or Placebo
Panel 3: BMS-986104 or Placebo
Panel 4: BMS-986104 or Placebo
Arm Description
BMS-986104 or Placebo single dose by mouth as specified
BMS-986104 or Placebo single dose by mouth as specified
BMS-986104 or Placebo single dose by mouth as specified
BMS-986104 or Placebo single dose by mouth as specified
Outcomes
Primary Outcome Measures
Incidence of all adverse events (AEs) / serious adverse events (SAEs)
Mean difference in ECG heart rate (HR) nadir values
Nadir absolute lymphocyte count (ALC) defined as the lowest ALC measured at any time after the dose
Secondary Outcome Measures
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
Mean difference in ECG HR values in BMS-986104-treated versus placebo-treated healthy male subjects, identifying nadir ECG HR
Percent reduction in ECG HR
Time to nadir ECG HR
Maximum observed blood concentration (Cmax) of BMS-986104
Time of maximum observed blood concentration (Tmax) of BMS-986104
Terminal half-life (T-HALF) of BMS-986104
Area under the blood concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986104
Area under the blood concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986104
Apparent total clearance (CLT/F) of BMS-986104
Apparent volume of distribution of terminal phase (Vz/F) of BMS-986104
Metabolite to parent AUC(INF) ratio [MR_AUC(INF)] for both BMS-986104 and BMT-019434
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
Full Information
NCT ID
NCT02211469
First Posted
August 6, 2014
Last Updated
September 16, 2015
Sponsor
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT02211469
Brief 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
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
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panel 1: BMS-986104 or Placebo
Arm Type
Experimental
Arm Description
BMS-986104 or Placebo single dose by mouth as specified
Arm Title
Panel 2: BMS-986104 or Placebo
Arm Type
Experimental
Arm Description
BMS-986104 or Placebo single dose by mouth as specified
Arm Title
Panel 3: BMS-986104 or Placebo
Arm Type
Experimental
Arm Description
BMS-986104 or Placebo single dose by mouth as specified
Arm Title
Panel 4: BMS-986104 or Placebo
Arm Type
Experimental
Arm Description
BMS-986104 or Placebo single dose by mouth as specified
Intervention Type
Drug
Intervention Name(s)
BMS-986104
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Incidence of all adverse events (AEs) / serious adverse events (SAEs)
Time Frame
Up to 1 month post discharge
Title
Mean difference in ECG heart rate (HR) nadir values
Time Frame
Up to 4 days postdose
Title
Nadir absolute lymphocyte count (ALC) defined as the lowest ALC measured at any time after the dose
Time Frame
Up to 4 days postdose
Secondary Outcome Measure Information:
Title
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
Title
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
Title
Percent reduction in ECG HR
Time Frame
Day -1 up to 24h and Days 1-5
Title
Time to nadir ECG HR
Time Frame
Day -1 up to 24h and Days 1-5
Title
Maximum observed blood concentration (Cmax) of BMS-986104
Time Frame
Up to Day 56
Title
Time of maximum observed blood concentration (Tmax) of BMS-986104
Time Frame
Up to Day 56
Title
Terminal half-life (T-HALF) of BMS-986104
Time Frame
Up to Day 56
Title
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
Title
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
Title
Apparent total clearance (CLT/F) of BMS-986104
Time Frame
Up to Day 56
Title
Apparent volume of distribution of terminal phase (Vz/F) of BMS-986104
Time Frame
Up to Day 56
Title
Metabolite to parent AUC(INF) ratio [MR_AUC(INF)] for both BMS-986104 and BMT-019434
Time Frame
Up to Day 56
Title
Effects of single oral doses of BMS-986104 on the following ALC
Description
Time to nadir ALC from time 0h (predose)
Percent reduction in ALC from baseline to nadir
Time Frame
Up to 4 days postdose
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Covance Clinical Research Unit, Inc.
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53704
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource
Learn more about this trial
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
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