Clinical trial NCT06723535: A Study to Evaluate BMS-986278 in Participants With Normal Renal Function, Severe Renal Impairment, or End-Stage Renal Disease on Intermittent Hemodialysis
Official title: An Open-Label, Single-Dose, Phase 1 Study to Evaluate the Pharmacokinetics and Safety of BMS-986278 in Participants With Normal Renal Function, Participants With Severe Renal Impairment, and Participants With End-Stage Renal Disease on Intermittent Hemodialysis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Kidney Failure, Chronic
Healthy Volunteers
Renal Impairment
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2024-12-09
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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/exclusion criteria apply.

Primary outcomes:
measure: Maximum observed concentration (Cmax)
timeFrame: Up to Day 8
measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)]
timeFrame: Up to Day 8
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)]
timeFrame: Up to Day 8
Secondary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Up to 28 days following discontinuation of dosing
measure: Number of participants with physical examination abnormalities
timeFrame: Up to Day 8
measure: Number of participants with vital sign abnormalities
timeFrame: Up to Day 8
measure: Number of participants with 12-lead electrocardiogram (ECG) abnormalities
timeFrame: Up to Day 8
measure: Number of participants with clinical laboratory abnormalities
timeFrame: Up to Day 8
measure: Time of maximum observed concentration (Tmax)
timeFrame: Up to Day 8
measure: Terminal elimination half-life (T-HALF)
timeFrame: Up to Day 8
measure: Apparent body clearance (CLT/F)
timeFrame: Up to Day 8
measure: Apparent volume of distribution of terminal phase (Vz/F)
timeFrame: Up to Day 8
measure: Concentration of BMS-986278 in dialysate
timeFrame: Up to Day 8
measure: Total amount recovered in dialysate (DR)
timeFrame: Up to Day 8
measure: Total percent of administered dose recovered in dialysate (%DR)
timeFrame: Up to Day 8
measure: Free fraction of unbound drug (Fu)
timeFrame: Up to Day 8
measure: Unbound Cmax (Cmax_u)
timeFrame: Up to Day 8
measure: Unbound AUC(0-T) (AUC(0-T) _u)
timeFrame: Up to Day 8
measure: Unbound AUC(INF) (AUC(INF)_u)
timeFrame: Up to Day 8
measure: Unbound CLT/F (CLT/F_u)
timeFrame: Up to Day 8
measure: Unbound Vz/F (Vz/F_u)
timeFrame: Up to Day 8
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology Of Miami, LLC
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
city: Orlando
country: United States
facility: Omega Research Group, LLC - Orlando
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: