MedPath

A Study to Evaluate Safety of Single Doses of BMS-986177 in Patients With End Stage Renal Disease (ESRD) Treated With Hemodialysis

Phase 1
Completed
Conditions
Antithrombotic
Interventions
Registration Number
NCT03000673
Lead Sponsor
Bristol-Myers Squibb
Brief Summary

To investigate safety of Single Doses of BMS-986177 in Patients with End Stage Renal Disease treated with hemodialysis

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
Inclusion Criteria
  • Subjects with ESRD treated with hemodialysis 3 times a week for at least 3 months prior enrollment.
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
  • Women must not be breastfeeding
  • Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) BMS-986177 plus 5 half-lives of study treatment (2 days) plus 30 days (duration of ovulatory cycle) for a total of 32 days post-treatment completion
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) BMS-986177 plus 5 half-lives of the study treatment plus 90 days (duration of sperm turnover) for a total of 92 days post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.
Exclusion Criteria
  • Subjects receiving dialysis through central venous catheters
  • History of uncontrolled or unstable cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematopoietic, psychiatric and/or neurological disease in the past 3 months
  • Current or recent (within 3 months of study drug administration) gastrointestinal disease or surgery, which by the judgment of the Investigator, may increase a subject's risk of gastrointestinal bleeding or interfere with absorption of study drug (e.g., peptic or gastric ulcer disease, severe gastritis, history of gastrointestinal surgery).
  • Any major surgery within 12 weeks of study drug administration
  • History of significant head injury within the last 2 years, including subjects with base of skull fractures

Other protocol defined inclusion/exclusion criteria could apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Dose Sequence 1EnoxaparinUFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin
Dose Sequence 1unfractionated heparin (UFH)UFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin
Dose Sequence 1BMS-986177UFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin
Dose Sequence 2unfractionated heparin (UFH)BMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2
Dose Sequence 2BMS-986177BMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2
Dose Sequence 3EnoxaparinBMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1
Dose Sequence 3unfractionated heparin (UFH)BMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1
Dose Sequence 4EnoxaparinEnoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH
Dose Sequence 4BMS-986177Enoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH
Dose Sequence 4unfractionated heparin (UFH)Enoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH
Dose Sequence 3BMS-986177BMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1
Dose Sequence 2EnoxaparinBMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2
Primary Outcome Measures
NameTimeMethod
The Number of Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Discontinuation and DeathFrom the date of patient's written consent to participate in study until 30 days after discontinuation of dosing or patient's participation in study (up to October 2017)

Safety and tolerability of single oral doses of BMS-986177 in patients with end-stage renal disease (ESRD) on chronic hemodialysis (HD) treatment as measured by the number of participants with adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation and death

The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.) : Liver and Kidney FunctionAt screening; On Day -3 to Day -1, 3 to 6 hours post HD on Days 1, 5, 8, and 12; and at study discharge.

LIVER \& KIDNEY FUNCTION; ALKALINE PHOSPHATASE (ALP) ALP U/L HIGH \> 1.25\*ULN IF PRE-RX IS MISSING; \> 1.25\*ULN IF PRE-RX \<= ULN; \> 1.25\*PRE-RX IF PRE-RX \> ULN; ASPARTATE AMINOTRANSFERASE (AST) AST U/L HIGH \> 1.25\*ULN IF PRE-RX IS MISSING; \> 1.25\*ULN IF PRE-RX \<= ULN; \> 1.25\*PRE-RX IF PRE-RX \> ULN; ALANINE AMINOTRANSFERASE (ALT) ALT U/L HIGH \> 1.25\*ULN IF PRE-RX IS MISSING; \> 1.25\*ULN IF PRE-RX \<= ULN; \> 1.25\*PRE-RX IF PRE-RX \> ULN; BILIRUBIN, TOTAL TBILI MG/DL HIGH \> 1.1\*ULN IF PRE-RX IS MISSING; \> 1.1\*ULN IF PRE-RX \<= ULN; \> 1.25\*PRE-RX IF PRE-RX \> ULN; BILIRUBIN, DIRECT DBILI MG/DL HIGH \> 1.1\*ULN IF PRE-RX IS MISSING; \> 1.1\*ULN IF PRE-RX \<= ULN; \> 1.25\*PRE-RX IF PRE-RX \> ULN; BLOOD UREA NITROGEN BUN MG/DL HIGH \> 1.1\*ULN IF PRE-RX IS MISSING; \> 1.1\*ULN IF PRE-RX \<= ULN; \> 1.2\*PRE-RX IF PRE-RX \> ULN; CREATININE CREAT MG/DL HIGH \> 1.5\*ULN IF PRE-RX IS MISSING; \> 1.5\*ULN IF PRE-RX \<= ULN; \> 1.33\*PRE-RX IF PRE-RX \> ULN;

The Number of Participants Marked Abnormalities in Clinical Laboratory Tests : Hematology I; Hematology II; CoagulationAt screening; On Day -3 to Day -1, 3 to 6 hours post HD on Days 1, 5, 8, and 12; and at study discharge.

HEMATOLOGY I; HEMOGLOBIN HB G/DL LOW \< 0.85\*PRE-RX; HEMATOCRIT HCT % LOW \< 0.85\*PRE-RX; PLATELET COUNT PLAT X10\*9 C/L LOW \< 0.85\*LLN IF PRE-RX IS MISSING; \< 0.85\*LLN IF PRE-RX \>= LLN; \< 0.85\*PRE-RX IF PRE-RX \< LLN; HIGH \> 1.5\*ULN; HEMATOLOGY II; LEUKOCYTES WBC X10\*3 C/UL LOW \< 0.9\*LLN IF PRE-RX IS MISSING; \< 0.9\*LLN IF LLN \<= PRE-RX \<= ULN; \< 0.85\*PRE-RX IF PRE-RX \< LLN; \< LLN IF PRE-RX \> ULN; HIGH \> 1.2\*ULN IF PRE-RX IS MISSING; \> 1.2\*ULN IF LLN \<= PRE-RX \<= ULN; \> 1.5\*PRE-RX IF PRE-RX \> ULN; NEUTROPHILS (ABSOLUTE) NEUTA X10\*3 C/UL LOW \< 1.5 IF PRE-RX IS MISSING; \< 1.5 IF PRE-RX \>= 1.5; \< 0.85\*PRE-RX IF; PRE-RX \< 1.5; LYMPHOCYTES (ABSOLUTE) LYMPA X10\*3 C/UL LOW \< 0.75; HIGH \> 7.5; MONOCYTES (ABSOLUTE) MONOA X10\*3 C/UL HIGH \> 2; BASOPHILS (ABSOLUTE) BASOA X10\*3 C/UL HIGH \> 0.4; EOSINOPHILS (ABSOLUTE) EOSA X10\*3 C/UL HIGH \> 0.75; COAGULATION: PROTHROMBIN TIME (PT) PT SEC HIGH \> 1.5\*ULN; APTT APTT SEC HIGH \> 1.5\*ULN; INTL NORMALIZED RATIO (INR) INR FRACTION HIGH \> 1.5\*ULN;

The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.): ElectrolytesAt screening; On Day -3 to Day -1, 3 to 6 hours post HD on Days 1, 5, 8, and 12; and at study discharge

ELECTROLYTES: SODIUM, SERUM NA MEQ/L LOW \< 0.95\*LLN IF PRE-RX IS MISSING; \< 0.95\*LLN IF PRE-RX \>= LLN; \< 0.95\*PRE-RX IF PRE-RX \< LLN; \< LLN IF PRE-RX \> ULN; HIGH \> 1.05\*ULN IF PRE-RX IS MISSING; \> 1.05\*ULN IF PRE-RX \<= ULN; \> 1.05\*PRE-RX IF PRE-RX \> ULN; \> ULN IF PRE-RX \< LLN; POTASSIUM, SERUM K MEQ/L LOW \< 0.9\*LLN IF PRE-RX IS MISSING; \< 0.9\*LLN IF PRE-RX \>= LLN; \< 0.9\*PRE-RX IF PRE-RX \< LLN; \< LLN IF PRE-RX \> ULN; HIGH \> 1.1\*ULN IF PRE-RX IS MISSING; \> 1.1\*ULN IF PRE-RX \<= ULN; \> 1.1\*PRE-RX IF PRE-RX \> ULN; \> ULN IF PRE-RX \< LLN; CHLORIDE, SERUM CL MEQ/L LOW \< 0.9\*LLN IF PRE-RX IS MISSING; \< 0.9\*LLN IF PRE-RX \>= LLN; \< 0.9\*PRE-RX IF PRE-RX \< LLN; \< LLN IF PRE-RX \> ULN; HIGH \> 1.1\*ULN IF PRE-RX IS MISSING; \> 1.1\*ULN IF PRE-RX \<= ULN; \> 1.1\*PRE-RX IF PRE-RX \> ULN; \> ULN IF PRE-RX \< LLN;

The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.): Other Chemistry TestingAt screening; On Day -3 to Day -1, 3 to 6 hours post HD on Days 1, 5, 8, and 12; and at study discharge.

GLUCOSE, FASTING SERUM GLUCF MG/DL LOW \< 0.8\*LLN IF PRE-RX IS MISSING; \< 0.8\*LLN IF PRE-RX \>= LLN; \< 0.8\*PRE-RX IF PRE-RX \< LLN; \< LLN IF PRE-RX \> ULN; HIGH \> 1.3\*ULN IF PRE-RX IS MISSING \> 1.3\*ULN IF PRE-RX \<= ULN; \> 2\*PRE-RX IF PRE-RX \> ULN; \> ULN IF PRE-RX \< LLN; PROTEIN, TOTAL TPRO G/DL LOW \< 0.9\*LLN IF PRE-RX IS MISSING; \< 0.9\*LLN IF PRE-RX \>= LLN; \< 0.9\*PRE-RX IF PRE-RX \< LLN; \< LLN IF PRE-RX \> ULN HIGH \> 1.1\*ULN IF PRE-RX IS MISSING; \> 1.1\*ULN IF PRE-RX \<= ULN; \> 1.1\*PRE-RX IF PRE-RX \> ULN; \> ULN IF PRE-RX \< LLN; ALBUMIN ALB G/DL LOW \< 0.9\*LLN IF PRE-RX IS MISSING; \< 0.9\*LLN IF PRE-RX \>= LLN; \< 0.9\*PRE-RX IF PRE-RX \< LLN; CREATINE KINASE (CK) CK U/L HIGH \> 1.5\*ULN IF PRE-RX IS MISSING; \> 1.5\*ULN IF PRE-RX \<= ULN; \> 1.5\*PRE-RX IF PRE-RX \> ULN; URIC ACID URIC MG/DL HIGH \> 1.2\*ULN IF PRE-RX IS MISSING; \> 1.2\*ULN IF PRE-RX \<= ULN; \> 1.25\*PRE-RX IF PRE-RX \> ULN; LACTATE DEHYDR (LD) LD U/L HIGH \> 1.25\*ULN IF PRE-RX IS MISSING; \> 1.25\*ULN IF PRE-RX \<= ULN; \> 1.5\*PRE-RX IF PRE-RX \> ULN

The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.): Electrolytes (Cont.)At screening; On Day -3 to Day -1, 3 to 6 hours post HD on Days 1, 5, 8, and 12; and at study discharge.

ELECTROLYTES (CONT.): CALCIUM, TOTAL CA MG/DL LOW \< 0.9\*LLN IF PRE-RX IS MISSING; \< 0.9\*LLN IF PRE-RX \>= LLN; \< 0.9\*PRE-RX IF PRE-RX \< LLN; \< LLN IF PRE-RX \> ULN; HIGH \> 1.1\*ULN IF PRE-RX IS MISSING; \> 1.1\*ULN IF PRE-RX \<= ULN; \> 1.1\*PRE-RX IF PRE-RX \> ULN; \> ULN IF PRE-RX \< LLN; PHOSPHORUS, INORGANIC PHOS MG/DL LOW \< 0.85\*LLN IF PRE-RX IS MISSING; \< 0.85\*LLN IF PRE-RX \>= LLN; \< 0.85\*PRE-RX IF PRE-RX \< LLN; \< LLN IF PRE-RX \> ULN; HIGH \> 1.25\*ULN IF PRE-RX IS MISSING; \> 1.25\*ULN IF PRE-RX \<= ULN; \> 1.25\*PRE-RX IF PRE-RX \> ULN; \> ULN IF PRE-RX \< LLN; MAGNESIUM, SERUM MG MEQ/L LOW \< 0.9\*LLN IF PRE-RX IS MISSING; \< 0.9\*LLN IF PRE-RX \>= LLN; \< 0.9\*PRE-RX IF PRE-RX \< LLN; \< LLN IF PRE-RX \> ULN; HIGH \> 1.1\*ULN IF PRE-RX IS MISSING; \> 1.1\*ULN IF PRE-RX \<= ULN; \> 1.1\*PRE-RX IF PRE-RX \> ULN; \> ULN IF PRE-RX \< LLN

The Change From Baseline in Vital Signs: Systolic Blood Pressure (mm Hg)Days -3 to -1, 1, 5, 8, 12 and at study discharge on day 13 to day 15
The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.) : Urinalysis I, Special StudiesAt screening; On Day -3 to Day -1, 3 to 6 hours post HD on Days 1, 5, 8, and 12; and at study discharge.

URINALYSIS I; BLOOD, URINE UBLD N/A HIGH \>= 2 IF PRE-RX IS MISSING; \>= 2 IF PRE-RX \< 1; \>= 2 IF PRE-RX \>= 1 SPECIAL STUDIES; OCCULT BLOOD SCREEN, FECES OCBLD N/A HIGH NEGATIVE PRE-RX CHANGING TO POSITIVE

The Change From Baseline in Electrocardiogram (ECG) Parameters: Mean Heart RateDays -3 to -1, Days 1, 5, 8, and 12.

Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.

The Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, AggregateDays -3 to -1, Days 1, 5, 8, and 12.

Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.

The Change From Baseline in Electrocardiogram (ECG) Parameters: QRS Duration, AggregateDays -3 to -1, Days 1, 5, 8, and 12.

Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.

The Change From Baseline in Electrocardiogram (ECG) Parameters: QT Interval, AggregateDays -3 to -1, Days 1, 5, 8, and 12.

Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.

The Change From Baseline in Electrocardiogram (ECG) Parameters: QTcF Interval, AggregateDays -3 to -1, Days 1, 5, 8, and 12

QTcF = QT corrected for heart rate using the Fridericia formula Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.

The Change From Baseline in Vital Signs: Diastolic Blood PressureDays -3 to -1, 1, 5, 8, 12 and at study discharge on day 13 to day 15
The Change From Baseline in Vital Signs: Heart Rate (Beats/Min)Days -3 to -1, 1, 5, 8, 12 and at study discharge on day 13 to day 15
Secondary Outcome Measures
NameTimeMethod
Pharmacokinetic Parameters of BMS-986177: Area Under the Concentration Curve AUC (0-T), AUC (0-24)Either Day 1, 5, 8, or 12 depending on the randomization sequence

AUC(0-T) Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration AUC(0-24) Area under the plasma concentration-time curve from time zero to 24 hours

Pharmacokinetic Parameters of BMS-986177: CmaxEither Day 1, 5, 8, or 12 depending on the randomization sequence

Cmax: Maximum observed plasma concentration

Pharmacokinetic Parameters of BMS-986177: TmaxEither Day 1, 5, 8, or 12 depending on the randomization sequence

Time of maximum observed plasma concentration

Pharmacokinetic Parameters of BMS-986177: CmaxfuEither Day 1, 5, 8, or 12 depending on the randomization sequence

Maximum observed plasma concentration of free drug

Pharmacokinetic Parameters of BMS-986177: Area Under the Concentration Curve AUC (0-T)fuEither Day 1, 5, 8, or 12 depending on the randomization sequence

AUC(0-T)fu Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration of free drug

Pharmacokinetic Parameters of BMS-986177: Area Under the Concentration Curve AUC (3-7)Either Day 1, 5, 8, or 12 depending on the randomization sequence

AUC (3-7) : Area under the plasma concentration-time curve from 3 to 7 hours (ie, during dialysis.

Determined from blood samples entering and exiting the dialyzer)

Pharmacokinetic Parameters of BMS-986177: fuEither Day 1, 5, 8, or 12 depending on the randomization sequence

Fraction of unbound drug

Trial Locations

Locations (2)

Davita Clinical Research

🇺🇸

Minneapolis, Minnesota, United States

Orlando Clinical Research Center

🇺🇸

Orlando, Florida, United States

Related Trials

© Copyright 2025. All Rights Reserved by MedPath
HomeTerms & ConditionsPrivacy Policy