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

A Study to Assess Safety and Tolerability of Single Oral Doses of BMS-986177 in Patients With ESRD Treated With Chronic Hemodialysis

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

Study Overview

• Status: Completed
• Conditions: Antithrombotic
• Intervention / Treatment: Drug: Enoxaparin; Drug: unfractionated heparin (UFH); Drug: BMS-986177

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • DaVita Clinical Research
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • DaVita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dose Sequence 1; UFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin	Drug: Enoxaparin; Specified dose of Enoxaparin on specified days; Drug: unfractionated heparin (UFH); Specified dose of UFH on specified days; Drug: BMS-986177; Specified dose of BMS-986177 on specified day
Active Comparator: Dose Sequence 2; BMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2	Drug: Enoxaparin; Specified dose of Enoxaparin on specified days; Drug: unfractionated heparin (UFH); Specified dose of UFH on specified days; Drug: BMS-986177; Specified dose of BMS-986177 on specified day
Active Comparator: Dose Sequence 3; BMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1	Drug: Enoxaparin; Specified dose of Enoxaparin on specified days; Drug: unfractionated heparin (UFH); Specified dose of UFH on specified days; Drug: BMS-986177; Specified dose of BMS-986177 on specified day
Active Comparator: Dose Sequence 4; Enoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH	Drug: Enoxaparin; Specified dose of Enoxaparin on specified days; Drug: unfractionated heparin (UFH); Specified dose of UFH on specified days; Drug: BMS-986177; Specified dose of BMS-986177 on specified day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Discontinuation and Death	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	From 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)
The Number of Participants Marked Abnormalities in Clinical Laboratory Tests : Hematology I; Hematology II; Coagulation	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;	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.
The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.) : Liver and Kidney Function	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;	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.
The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.): Electrolytes	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;	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
The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.): Electrolytes (Cont.)	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	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.
The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.): Other Chemistry Testing	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	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.
The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.) : Urinalysis I, Special Studies	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	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.
The Change From Baseline in Electrocardiogram (ECG) Parameters: Mean Heart Rate	Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.	Days -3 to -1, Days 1, 5, 8, and 12.
The Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, Aggregate	Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.	Days -3 to -1, Days 1, 5, 8, and 12.
The Change From Baseline in Electrocardiogram (ECG) Parameters: QRS Duration, Aggregate	Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.	Days -3 to -1, Days 1, 5, 8, and 12.
The Change From Baseline in Electrocardiogram (ECG) Parameters: QT Interval, Aggregate	Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.	Days -3 to -1, Days 1, 5, 8, and 12.
The Change From Baseline in Electrocardiogram (ECG) Parameters: QTcF Interval, Aggregate	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.	Days -3 to -1, Days 1, 5, 8, and 12
The Change From Baseline in Vital Signs: Diastolic Blood Pressure		Days -3 to -1, 1, 5, 8, 12 and at study discharge on day 13 to day 15
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 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

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameters of BMS-986177: Cmax	Cmax: Maximum observed plasma concentration	Either Day 1, 5, 8, or 12 depending on the randomization sequence
Pharmacokinetic Parameters of BMS-986177: Tmax	Time of maximum observed plasma concentration	Either Day 1, 5, 8, or 12 depending on the randomization sequence
Pharmacokinetic Parameters of BMS-986177: Area Under the Concentration Curve AUC (0-T), AUC (0-24)	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	Either Day 1, 5, 8, or 12 depending on the randomization sequence
Pharmacokinetic Parameters of BMS-986177: fu	Fraction of unbound drug	Either Day 1, 5, 8, or 12 depending on the randomization sequence
Pharmacokinetic Parameters of BMS-986177: Cmaxfu	Maximum observed plasma concentration of free drug	Either Day 1, 5, 8, or 12 depending on the randomization sequence
Pharmacokinetic Parameters of BMS-986177: Area Under the Concentration Curve AUC (0-T)fu	AUC(0-T)fu Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration of free drug	Either Day 1, 5, 8, or 12 depending on the randomization sequence
Pharmacokinetic Parameters of BMS-986177: Area Under the Concentration Curve AUC (3-7)	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)	Either Day 1, 5, 8, or 12 depending on the randomization sequence

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2017
• Primary Completion (Actual): October 23, 2017
• Study Completion (Actual): October 23, 2017

Study Registration Dates

• First Submitted: December 20, 2016
• First Submitted That Met QC Criteria: December 20, 2016
• First Posted (Estimate): December 22, 2016

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 3, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Enoxaparin; Calcium heparin
• Other Study ID Numbers: CV010-010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No