Clinical trial NCT03281122: A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction
Official title: A Randomized, Double-Blinded, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986224 in Healthy Subjects and Chronic Heart Failure Patients With Reduced Ejection Fraction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Heart Failure
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-09-13
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is test the safety and tolerability of BMS-986224 and its effects on the body in healthy subjects and subjects with chronic heart failure with reduced ejection fraction


Eligibility criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

Healthy Subjects (Part A and B)

* Healthy subjects, as determined by no clinically significant deviations in medical history, physical examination, ECGs, vital signs, and clinical laboratory determinations
* Subjects must be willing and able to complete all study-specific procedures and visits
* Additional criterion for Japanese subjects in Groups BJ1 to BJ3: Subjects must be first generation Japanese (born in Japan and not living outside of Japan for \> 10 years, and both parents are ethnically Japanese)

Heart Failure Patients (Part C)

* Left ventricular EF \<45% and \>25%, as assessed by cardiac MRI within 3 months of first dose of study drug; or left ventricular EF \<40% and \>25% as assessed by echocardiogram at Screening or within 3 months of first dose of study drug; left ventricular EF
* Heart failure is considered to be stable at the discretion of the Investigator (i.e., no acute cardiovascular \[CV\] events or hospitalization (including emergency room visits) for CV causes within 3 months of first dose of study drug
* Regular sinus rhythm at Screening and no history of atrial fibrillation in the past 12 months

Exclusion Criteria:

Healthy Subjects (Part A and B)

* Major surgery within 4 weeks of (first) study treatment administration
* Inability to be venipunctured and/or tolerate venous access
* Subjects who have smoked or used smoking cessation or nicotine containing products (including, but not limited, to e-cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum, varenicline, bupropion) within 6 months of the first dose of study drug

Heart Failure Patients (Part C)

* Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could affect absorption
* Major surgery within 4 weeks of (first) study treatment administration
* Inability to be venipunctured and/or tolerate venous access

Other protocol defined inclusion/exclusion criteria could apply

Primary outcomes:
measure: Number of Serious Adverse Events (SAEs)
timeFrame: Up to one month
measure: Number of Adverse Events (AEs)
timeFrame: Up to one month
measure: Number of deaths
timeFrame: Up to one month
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to one month
measure: Time of maximum observed plasma concentration (Tmax)
timeFrame: Up to one month
measure: Terminal elimination half-life (T-HALF)
timeFrame: Up to one month
measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)]
timeFrame: Up to one month
measure: Area under the plasma concentration-time curve from time zero extrapoloated [AUC(INF)]
timeFrame: Up to one month
measure: Area under the concentration-time curve in one dosing interval [AUC(TAU)]
timeFrame: Up to one month
measure: Accumulation ratio: ratio of Cmax following last dose to Cmax following first dose (ARcmax)
timeFrame: Up to one month
measure: Accumulation ratio: ratio of AUC(TAU) following last dose to AUC(TAU) following first dose (ARtau)
timeFrame: Up to one month
measure: Terminal elimination rate constant (kel)
timeFrame: Up to one month
measure: Apparent oral clearance, calculated as dose/AUC(INF) for single dose or dose/AUC(TAU) for multiple dose
timeFrame: Up to one month
measure: Apparent volume of distribution at terminal phase (Vz/F)
timeFrame: Up to one month
measure: Cumulative urinary excretion (of the unchanged drug) over one dosing interval [Ae(TAU)]
timeFrame: Up to one month
measure: Cumulative urinary excretion (of the unchanged drug) [Aet]
timeFrame: Up to one month
measure: Renal clearance (CLr)
timeFrame: Up to one month
measure: Amount excreted unchanged (%) [UR%]
timeFrame: Up to one month
measure: Ratio of Metabolite Cmax to Parent Cmax, corrected for molecular weight (MR_Cmax)
timeFrame: Up to one month
measure: Ratio of Metabolite AUC(INF) to Parent AUC(INF), corrected for molecular weight
timeFrame: Up to one month
measure: Ratio of Metabolite AUC(0-T) to Parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)]
timeFrame: Up to one month
measure: Ratio of Metabolite AUC(TAU) to Parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)]
timeFrame: Up to one month
measure: Drug-drug interaction (DDI) assessment
timeFrame: Up to one month
Other outcomes:
Locations:
city: Praha 2
country: Czechia
facility: Vseobecna Fakultni Nemocnice v Praze
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni - Masarykova nemocnice v Usti nad Labem
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Groningen
country: Netherlands
facility: PRA Health Sciences - Groningen
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis - Haarlem-Zuid
city: Sneek
country: Netherlands
facility: D & A Research and Genetics
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Number 4 w Lublinie
city: Wroclaw
country: Poland
facility: 4th Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Dundee
country: United Kingdom
facility: NHS Tayside
city: Edinburgh
country: United Kingdom
facility: The University of Edinburgh
city: London
country: United Kingdom
facility: Richmond Pharmacology
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: