A double-blind, placebo-controlled, randomized, single and multiple ascending dose study of the safety and tolerability, and pharmacokinetics (including food effect, pH effect and Japanese bridging study) of BMS-986337 following oral administration in healthy participants
- Conditions
- idiopathic pulmonary fibrosis
- Registration Number
- NL-OMON49565
- Lead Sponsor
- Bristol-Myers Squibb Research and Development
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 78
1) Signed Written Informed Consent
a) Participants must be willing and able to participate in the study and sign
the informed
consent form (ICF).
b) Participants must be willing and able to complete all study-specific
procedures and visits.
2) Type of Participant and Target Disease Characteristics
a) Healthy participant, as determined by no clinically significant deviation
from normal in
medical history, physical examination, ECGs, and clinical laboratory
determinations.
b) Participants in the Japanese cohorts in Part C must be first-generation
Japanese (born in
Japan, not living outside of Japan for more than 10 years, and both parents are
ethnically
Japanese).
c) Body mass index (BMI) of 18.0 kg/m2 to 30.0 kg/m2, inclusive, at screening.
BMI = weight (kg)/height (m)2
d) Body weight between 50 kg and 120 kg, inclusive, at screening.
e) Normal renal function at screening (and study admission) as evidenced by an
estimated glomerular filtration rate (eGFR) >= 80 mL/min/1.732 m2 calculated
with the Chronic Kidney Disease Epidemiology Collaboration formula.
GFR = 141 × (min(SCr/*,1)a × max (SCr/*,1) -1.209 × 0.993Age × 1.018 [if
female] ×
1.159 [if black]) Where SCr is serum creatinine (mg/dL), * is 0.7 for females
and 0.9 for males, a
is -0.329 for females and -0.411 for males, min indicates the minimum of SCr/*
or 1, and max indicates the maximum of SCr/* or 1.
3) Age and Reproductive Status
a) Female Participants:
i) Females, ages 21 to 65 years, inclusive.
ii) Women participants must have documented proof that they are not of
childbearing potential (refer to APPENDIX 4).
iii) A female participant is eligible to participate if she is not pregnant or
breastfeeding, and is not a WOCBP.
iv) Women who are not of childbearing potential are exempt from contraceptive
requirements.
b) Male Participants:
i) Males, ages 21 to 65 years, inclusive.
ii) Males who are sexually active with WOCBP must agree to follow instructions
for method(s) of contraception defined in APPENDIX 4 and as described below.
iii) Azoospermic males are not exempt from contraceptive requirements and will
be required to always use a latex or other synthetic condom during any sexual
activity (eg, vaginal, anal, oral) with WOCBP even if the participant has
undergone a successful vasectomy or if the partner is pregnant.
iv) Male participants will be required to always use a latex or other synthetic
condom during any sexual activity (eg, vaginal, anal, oral) with WOCBP; even if
the participants have undergone a successful vasectomy or if their partner is
already pregnant or breastfeeding. Males should continue to use a condom during
the study treatment period and for at least 5 days after the last dose of study
treatment.
v) Male participants with a pregnant or breastfeeding partner must agree to
remain abstinent from sexual activity or use a male condom during any sexual
activity (eg, vaginal, anal, oral) even if the participants have undergone a
successful vasectomy, during the study treatment period and for at least 5 days
after the last dose of study treatment.
vi) Female partners of males participating in the study should be advised to
use highly effective methods of contraception during the study treatment period
and for at least 5 days after the last dose of stu
1) Medical Conditions
a) Women who are of childbearing potential.
b) Women who are breastfeeding.
c) Any significant acute or chronic medical condition that presents a potential
risk to the participant and/or that may compromise the objectives of the study,
including active, or history of, liver disease, or intestinal disorder
including irritable bowel syndrome.
d) History or presence of malignancy including hematological malignancies;
participants with a history of basal cell or squamous cell carcinoma that has
been treated with no evidence of recurrence within 5 years will be allowed for
inclusion, as judged by the investigator.
e) History of significant cardiac disease (eg, hospitalization for congestive
heart failure, myocardial infarction, unstable angina, coronary angioplasty, or
coronary artery bypass graft within 6 months of screening) or uncontrolled
atrial or ventricular cardiac arrhythmias.
f) History of significant left ventricular dysfunction (ie, echocardiography
with ejection fraction of < 40%).
g) Current or recent (within 3 months of study treatment administration)
gastrointestinal disease that could impact upon the absorption of study
treatment.
h) Any major surgery within 6 weeks of study treatment administration.
i) Any gastrointestinal surgery, including cholecystectomy, that, in the
opinion of the investigator, could impact upon the absorption of study
treatment.
j) Documented congenital QT syndrome, and/or corrected QT-interval (Fridericia
correction,
QTcF) at screening or first admission > 450 msec.
k) Donation or loss of more than 450 mL of blood within 2 months prior to (the
first) study
treatment administration.
l) Blood transfusion within 4 weeks of study treatment administration.
m) Inability to tolerate oral medication.
n) Inability to be venipunctured and/or tolerate venous access.
o) Participants 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 3 months of
the first dose of study treatment.
p) Recent (within 6 months of study treatment administration) drug or alcohol
abuse as defined in Diagnostic and Statistical Manual of Mental Disorders 4th
edition (DSM-IV),13 Diagnostic Criteria for Drug and Alcohol Abuse.
q) Average intake of more than 21 units of alcohol (1 unit of alcohol equals
approximately 12 oz of beer, 5 oz of wine, or 1.5 oz of spirits) per week
within the last 6 months at the screening visit. After screening, participants
are permitted to consume an average intake of <= 14 units of alcohol per week
until the day of study admission.
r) Any other medical, psychiatric, and/or social reason as determined by the
investigator.
2) Prior/Concomitant Therapy
a) Prior exposure to BMS-986278.
b) Inability to comply with restrictions and prohibited treatments as listed in
Section 6.7.
c) Use of any prescription drugs or over-the-counter (OTC) gastric acid
controllers within 4
weeks prior to study treatment administration except those medications cleared
by the investigator and PRA Medical Monitor.
d) Use of any OTC medications and herbal preparations within 2 weeks prior to
study treatment administration (except
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs<br /><br>leading to discontinuation<br /><br><br /><br>Results of clinical laboratory values, vital signs, electrocardiograms (ECGs),<br /><br>physical examinations</p><br>
- Secondary Outcome Measures
Name Time Method <p>Plasma concentrations of BMS-986337, and its acylglucuronide (BMT-405951) and<br /><br>amine (BMT-385617) metabolites; derived PK parameters as applicable<br /><br><br /><br>Plasma concentrations of BMS-986337, and its BMT-405951 and BMT-385617<br /><br>metabolites, following a high-fat meal and pH modulation; derived<br /><br>PK parameters as applicable<br /><br><br /><br>Plasma concentrations of BMS-986337, and its BMT-405951 and BMT-385617<br /><br>metabolites in Japanese and non- Japanese participants; derived PK<br /><br>parameters as applicable</p><br>