Clinical trial NCT02145234: Placebo-Controlled, Single and Multiple Ascending Subcutaneous Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986089 in Healthy Adult Subjects
Official title: A Randomized, Placebo-Controlled, Single and Multiple Ascending Subcutaneous Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986089 in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adults
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-05-22
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of single and multiple doses of BMS-986089 in healthy adult subjects.

Detailed description: Primary Purpose - other: Protocol designed to assess the safety, tolerability, immunogenicity, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BMS-986089 in healthy subjects

Enrollment: Single ascending dose panels: 48 subjects, Multiple ascending dose panels: 96

Minimum age: 18 years (Elderly MAD Panel 65 years of age) Maximum age: 55 years (Elderly MAD Panel 70 years of age)

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

Inclusion Criteria:

* Healthy subjects as determined by no clinically significant deviation from normal medical history, physical examination, ECGs and clinical laboratory determinations
* Men and women who are not of childbearing potential (ie, who are postmenopausal or Surgically sterile WOCBP) ages 21 to 55 years
* Women must not be breastfeeding
* Men who are sexually active with women of child bearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year

Exclusion Criteria:

* Any significant acute or chronic medical illness Any major surgery within 6 weeks of study drug administration
* Any condition that will clearly require medical or surgical treatment during the period of study participation
* Any bone trauma or bone surgery within 3 months of study drug administration
* Known or suspected autoimmune disorder
* Donation of blood or plasma to a blood bank or in a clinical study (except at screening visit) within 6 weeks of study

Primary outcomes:
measure: Safety endpoints, including incidence of Adverse Event (AEs), serious AEs, AEs leading to discontinuation or death, as well as marked abnormalities in clinical laboratory tests, vital sign measurements, ECGs, and physical examinations
timeFrame: Single Ascending Dose (SAD) Phase 119 days
measure: Safety endpoints, including incidence of Adverse Event (AEs), serious AEs, AEs leading to discontinuation or death, as well as marked abnormalities in clinical laboratory tests, vital sign measurements, ECGs, and physical examinations
timeFrame: Multiple Ascending Dose (MAD) phase 148 days
Secondary outcomes:
measure: Maximum observed serum concentration (Cmax) for SAD and MAD
timeFrame: SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
measure: Time of maximum observed serum concentration (Tmax) for SAD and MAD
timeFrame: SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
measure: Serum concentration 168 h post dose (C(168H)) for SAD and MAD
timeFrame: SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
measure: Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) for SAD
timeFrame: SAD phase: Day1 to Day 91
measure: Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) for SAD
timeFrame: SAD phase: Day1 to Day 91
measure: Apparent total body clearance (CLT/F) for SAD
timeFrame: SAD phase: Day1 to Day 91
measure: Volume of distribution of terminal phase (if IV and if multi-exponential decline) (Vz/F) for SAD
timeFrame: SAD phase: Day1 to Day 91
measure: Half life (T-Half) for SAD and MAD
timeFrame: SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
measure: Serum concentration 336 h post dose (C(336H)) for SAD and MAD
timeFrame: SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
measure: Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff_AUC) for MAD
timeFrame: MAD phase: Day 1 to Day 120
measure: Area under the concentration-time curve in one dosing interval (AUC(TAU)) for MAD
timeFrame: MAD phase: Day 1 to Day 120
measure: Degree of Fluctuation or Fluctuation Index (DF) for MAD
timeFrame: MAD phase: Day 1 to Day 120
measure: Average concentration over a dosing interval (Css-Avg) for MAD
timeFrame: MAD phase: Day 1 to Day 120
measure: AUC Accumulation Index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI AUC) for MAD
timeFrame: MAD phase: Day 1 to Day 120
measure: Cmax Accumulation Index; ratio of Cmax at steady-state to Cmax after the first dose (AI Cmax) for MAD
timeFrame: MAD phase: Day 1 to Day 120
measure: C(168H) Accumulation Index; ratio of C168H at steady-state to C168H after the first dose (AI C168H) for MAD
timeFrame: MAD phase: Day 1 to Day 120
measure: C(336H) Accumulation Index; ratio of C(336H) at steady-state to C(336H) after the first dose (AI 336H) for MAD
timeFrame: MAD phase: Day 1 to Day 120
measure: Immunogenicity of single and multiple doses of BMS-986089 will be measured by testing for the presence of ADAs for SAD and MAD
timeFrame: 30 days
measure: The pharmacodynamic effect of single and multiple doses of BMS-986089 on free myostatin, total myostatin (pre-dose only), and myostatin-drug complex will be assessed by measuring these biomarkers for SAD and MAD
timeFrame: 30 days
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Wcct Global, Llc
state: California
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: