Placebo-Controlled, Single and Multiple Ascending Subcutaneous Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986089 in Healthy Adult Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Adults
• Intervention / Treatment: Drug: BMS-986089; Drug: Placebo matching with BMS-986089

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)

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT Global, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SAD Panel 1:BMS-986089/Placebo; BMS-986089 in a single subcutaneous administration OR Placebo matching with BMS-986089 in a single subcutaneous administration	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: SAD Panel 2:BMS-986089/Placebo; BMS-986089 in a single subcutaneous administration OR Placebo matching with BMS-986089 in a single subcutaneous administration	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: SAD Panel 3:BMS-986089/Placebo; BMS-986089 in a single subcutaneous administration OR Placebo matching with BMS-986089 in a single subcutaneous administration	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: SAD Panel 4:BMS-986089/Placebo; BMS-986089 in a single subcutaneous administration OR Placebo matching with BMS-986089 in a single subcutaneous administration	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: SAD Panel 5:BMS-986089/Placebo; BMS-986089 in a single subcutaneous administration OR Placebo matching with BMS-986089 in a single subcutaneous administration	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: MAD Panel 1:BMS-986089/Placebo; BMS-986089 in multiple subcutaneous administrations weekly OR Placebo matching with BMS-986089 multiple subcutaneous administrations weekly	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: MAD Panel 2:BMS-986089/Placebo; BMS-986089 in multiple subcutaneous administrations weekly OR Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: MAD Panel 3:BMS-986089/Placebo; BMS-986089 in multiple subcutaneous administrations weekly OR Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: MAD Panel 4:BMS-986089/Placebo; BMS-986089 in multiple subcutaneous administrations weekly OR Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: MAD Panel 5:BMS-986089/Placebo; BMS-986089 in multiple subcutaneous administration every 2 weeks OR Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: MAD Panel 6:BMS-986089/Placebo; BMS-986089 in multiple subcutaneous administrations weekly OR Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly	Drug: BMS-986089; Drug: Placebo matching with BMS-986089
EXPERIMENTAL: MAD Panel 7:BMS-986089/Placebo; BMS-986089 a single subcutaneous administrations weekly OR Placebo matching with BMS-986089 a single subcutaneous administration every 2 weeks	Drug: BMS-986089; Drug: Placebo matching with BMS-986089

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Single Ascending Dose (SAD) Phase 119 days
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	Multiple Ascending Dose (MAD) phase 148 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum observed serum concentration (Cmax) for SAD and MAD	SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
Time of maximum observed serum concentration (Tmax) for SAD and MAD	SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
Serum concentration 168 h post dose (C(168H)) for SAD and MAD	SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) for SAD	SAD phase: Day1 to Day 91
Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) for SAD	SAD phase: Day1 to Day 91
Apparent total body clearance (CLT/F) for SAD	SAD phase: Day1 to Day 91
Volume of distribution of terminal phase (if IV and if multi-exponential decline) (Vz/F) for SAD	SAD phase: Day1 to Day 91
Half life (T-Half) for SAD and MAD	SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
Serum concentration 336 h post dose (C(336H)) for SAD and MAD	SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120
Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff_AUC) for MAD	MAD phase: Day 1 to Day 120
Area under the concentration-time curve in one dosing interval (AUC(TAU)) for MAD	MAD phase: Day 1 to Day 120
Degree of Fluctuation or Fluctuation Index (DF) for MAD	MAD phase: Day 1 to Day 120
Average concentration over a dosing interval (Css-Avg) for MAD	MAD phase: Day 1 to Day 120
AUC Accumulation Index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI AUC) for MAD	MAD phase: Day 1 to Day 120
Cmax Accumulation Index; ratio of Cmax at steady-state to Cmax after the first dose (AI Cmax) for MAD	MAD phase: Day 1 to Day 120
C(168H) Accumulation Index; ratio of C168H at steady-state to C168H after the first dose (AI C168H) for MAD	MAD phase: Day 1 to Day 120
C(336H) Accumulation Index; ratio of C(336H) at steady-state to C(336H) after the first dose (AI 336H) for MAD	MAD phase: Day 1 to Day 120
Immunogenicity of single and multiple doses of BMS-986089 will be measured by testing for the presence of ADAs for SAD and MAD	30 days
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	30 days

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2014
• Primary Completion (ACTUAL): February 29, 2016
• Study Completion (ACTUAL): February 29, 2016

Study Registration Dates

• First Submitted: May 16, 2014
• First Submitted That Met QC Criteria: May 20, 2014
• First Posted (ESTIMATE): May 22, 2014

Study Record Updates

• Last Update Posted (ACTUAL): September 7, 2017
• Last Update Submitted That Met QC Criteria: September 5, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: CN001-001