Healthy Volunteers, Kidney Failure, Chronic, Renal Impairment
Conditions
Brief summary
The purpose of this study is to assess the effect of severe renal impairment (RI) and end-stage renal disease (ESRD) with intermittent hemodialysis (IHD) on the pharmacokinetics and safety of BMS-986278. This study plans to use a staged design based on RI severity.
Interventions
DRUGBMS-986278
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) between 18 and 45 kg/m2 inclusive, and body weight ≥ 50 kg at screening. Note: for ESRD participants, this body weight should be the prescription dry weight. * Severe Renal Impaired Participants: 1. Participant has a supine SBP ≥ 90 and ≤ 180 mmHg, supine DBP ≥ 60 and ≤ 100 mmHg, and heart rate ≥ 40 and ≤ 110 beats per minute. 2. Participant has severe RI as defined by an eGFR ˂ 30 mL/min and not requiring dialysis at screening. 3. Participant must be medically stable for at least 1 month before study intervention administration. * Participants with ESRD: 1. Participant has ESRD as defined by an eGFR \< 15 mL/min at screening. 2. Participant required to be on intermittent hemodialysis, an average of 3 hemodialysis treatments per week prior to screening. 3. Participant has demonstrated adequate hemodialysis measurements (at least 2 Kt/V measurements ≥ 1.2 or 2 urea reduction ratio measurements ≥ 65%) within the 3 months prior to screening. * Healthy participant should have a supine SBP ≥ 90 and ≤ 160 mm Hg, supine DBP ≥ 50 and ≤ 100 mm Hg, and heart rate ≥ 40 and ≤ 100 beats per minute. * Healthy participants should have normal renal function, as defined by having an eGFR ≥ 90 mL/min eGFR at screening (calculated using the CKD-EPI equation).
Exclusion criteria
* Participant with any significant medical condition, laboratory abnormality, or psychiatric illness. * Any surgical or medical condition(s) possibly affecting drug absorption, distribution, metabolism, or excretion (eg, bariatric procedure or cholecystectomy). * Individuals who are of childbearing potential, breastfeeding, or currently pregnant. * Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] | Up to Day 8 |
| Maximum observed concentration (Cmax) | Up to Day 8 |
| Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] | Up to Day 8 |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with 12-lead electrocardiogram (ECG) abnormalities | Up to Day 8 |
| Number of participants with clinical laboratory abnormalities | Up to Day 8 |
| Time of maximum observed concentration (Tmax) | Up to Day 8 |
| Terminal elimination half-life (T-HALF) | Up to Day 8 |
| Apparent body clearance (CLT/F) | Up to Day 8 |
| Apparent volume of distribution of terminal phase (Vz/F) | Up to Day 8 |
| Concentration of BMS-986278 in dialysate | Up to Day 8 |
| Number of participants with adverse events (AEs) | Up to 28 days following discontinuation of dosing |
| Total percent of administered dose recovered in dialysate (%DR) | Up to Day 8 |
| Free fraction of unbound drug (Fu) | Up to Day 8 |
| Unbound Cmax (Cmax_u) | Up to Day 8 |
| Unbound AUC(0-T) (AUC(0-T) _u) | Up to Day 8 |
| Unbound AUC(INF) (AUC(INF)_u) | Up to Day 8 |
| Unbound CLT/F (CLT/F_u) | Up to Day 8 |
| Unbound Vz/F (Vz/F_u) | Up to Day 8 |
| Total amount recovered in dialysate (DR) | Up to Day 8 |
| Number of participants with physical examination abnormalities | Up to Day 8 |
| Number of participants with vital sign abnormalities | Up to Day 8 |
Countries
United States
Outcome results
None listed