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unfractionated heparin

Phase 1

Antithrombotic | Small molecule | Other |Bristol-Myers Squibb Company|Last Updated: Dec 29, 2020

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedACTIVE_CONTROLLEDBiomarker
Total Trials1
Total Enrollment32
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03000673A Study to Evaluate Safety of Single Doses of BMS-986177 in Patients With End Stage Renal Disease (ESRD) Treated With HemodialysisPHASE1 COMPLETED 32May 23, 2017Oct 23, 2017Dec 29, 20203 United States
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Study Endpoints
Primary Endpoints
The Number of 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)

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 Participants Marked Abnormalities in Clinical Laboratory Tests : Hematology I; Hematology II; Coagulation
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.

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.) : Liver and Kidney Function
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.

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 Marked Abnormalities in Clinical Laboratory Tests (Cont.): Electrolytes
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: 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.): 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 Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.): Other Chemistry Testing
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.

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.) : Urinalysis I, Special Studies
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.

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 Rate
Days -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, Aggregate
Days -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, Aggregate
Days -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, Aggregate
Days -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, Aggregate
Days -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 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 Endpoints
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
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelCROSSOVER
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Dose Sequence 1ACTIVE_COMPARATORUFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin
Dose Sequence 2ACTIVE_COMPARATORBMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2
Dose Sequence 3ACTIVE_COMPARATORBMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1
Dose Sequence 4ACTIVE_COMPARATOREnoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH
Interventions
NameTypeDescription
EnoxaparinDRUGSpecified dose of Enoxaparin on specified days
unfractionated heparin (UFH)DRUGSpecified dose of UFH on specified days
BMS-986177DRUGSpecified dose of BMS-986177 on specified day
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Eligibility Criteria
Age Range18 Years — 75 Years
SexALL
Healthy VolunteersNo
Study Sites3

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 neg...

Countries:United States
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