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

NCT03000673 | Completed Phase 1 Results FDA Drug

• 1 other identifier: CV010-010
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Antithrombotic

Outcome Measures

Primary Outcomes (15)

• 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 Outcomes (7)

• Pharmacokinetic Parameters of BMS-986177: Cmax

  Either Day 1, 5, 8, or 12 depending on the randomization sequence

• Pharmacokinetic Parameters of BMS-986177: Tmax

  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)

  Either Day 1, 5, 8, or 12 depending on the randomization sequence

• Pharmacokinetic Parameters of BMS-986177: fu

  Either Day 1, 5, 8, or 12 depending on the randomization sequence

• Pharmacokinetic Parameters of BMS-986177: Cmaxfu

  Either Day 1, 5, 8, or 12 depending on the randomization sequence

Study Arms (4)

Dose Sequence 1

ACTIVE COMPARATOR

UFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin

Drug: Enoxaparin; Drug: unfractionated heparin (UFH); Drug: BMS-986177

Dose Sequence 2

ACTIVE COMPARATOR

BMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2

Drug: Enoxaparin; Drug: unfractionated heparin (UFH); Drug: BMS-986177

Dose Sequence 3

ACTIVE COMPARATOR

BMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1

Drug: Enoxaparin; Drug: unfractionated heparin (UFH); Drug: BMS-986177

Dose Sequence 4

ACTIVE COMPARATOR

Enoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH

Drug: Enoxaparin; Drug: unfractionated heparin (UFH); Drug: BMS-986177

Interventions

Enoxaparin DRUG

Specified dose of Enoxaparin on specified days

Dose Sequence 1; Dose Sequence 2; Dose Sequence 3; Dose Sequence 4

unfractionated heparin (UFH) DRUG

Specified dose of UFH on specified days

Dose Sequence 1; Dose Sequence 2; Dose Sequence 3; Dose Sequence 4

BMS-986177 DRUG

Specified dose of BMS-986177 on specified day

Dose Sequence 1; Dose Sequence 2; Dose Sequence 3; Dose Sequence 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (3)

Davita Clinical Research

Lakewood, Colorado, 80228, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Davita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

Related Links

• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form

MeSH Terms

Interventions

Enoxaparin; Heparin; milvexian

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: December 22, 2016
• Study Start: May 23, 2017
• Primary Completion: October 23, 2017
• Study Completion: October 23, 2017
• Last Updated: December 29, 2020
• Results First Posted: December 29, 2020

Record last verified: 2020-12

Locations

US (3)