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

Phase 2CompletedNCT03000673

Bristol-Myers Squibb32 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Antithrombotic

Interventions

EnoxaparinDRUG

Specified dose of Enoxaparin on specified days

unfractionated heparin (UFH)DRUG

Specified dose of UFH on specified days

BMS-986177DRUG

Specified dose of BMS-986177 on specified day

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (3)

Davita Clinical Research

Lakewood, Colorado, United States

Orlando Clinical Research Center

Orlando, Florida, United States

Davita Clinical Research

Minneapolis, Minnesota, United States

Outcomes

Primary Outcomes

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

Time frame: 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;

Time frame: 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;

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: 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;

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Days -3 to -1, Days 1, 5, 8, and 12

The Change From Baseline in Vital Signs: Diastolic Blood Pressure

Time frame: 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)

Time frame: 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)

Time frame: Days -3 to -1, 1, 5, 8, 12 and at study discharge on day 13 to day 15