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

Phase 1

Completed

• Conditions: Healthy Adults
• Interventions: Drug: BMS-986089; Drug: Placebo matching with BMS-986089

• Registration Number: NCT02145234
• Lead Sponsor: Hoffmann-La Roche

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)

Study Timeline

• Study First Submitted: 2014-05-16
• Study First Submitted QC: 2014-05-20
• Study First Posted: 2014-05-22
• Study Start: 2014-06-30
• Primary Completion: 2016-02-29
• Study Completion: 2016-02-29
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-05
• Last Update Posted: 2017-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 140

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Volume of distribution of terminal phase (if IV and if multi-exponential decline) (Vz/F) for SAD	SAD phase: Day1 to Day 91
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
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
Half life (T-Half) 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 serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) for SAD	SAD phase: Day1 to Day 91
Average concentration over a dosing interval (Css-Avg) for MAD	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
Apparent total body clearance (CLT/F) for SAD	SAD phase: Day1 to Day 91
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
Area under the concentration-time curve in one dosing interval (AUC(TAU)) 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
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
Degree of Fluctuation or Fluctuation Index (DF) 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
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

Trial Locations

Locations (1)

Wcct Global, Llc; 🇺🇸 Cypress, California, United States