Antithrombotic Clinical Trial
Official title:
A Study to Assess Safety and Tolerability of Single Oral Doses of BMS-986177 in Patients With ESRD Treated With Chronic Hemodialysis
Verified date | December 2020 |
Source | Bristol-Myers Squibb |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
To investigate safety of Single Doses of BMS-986177 in Patients with End Stage Renal Disease treated with hemodialysis
Status | Completed |
Enrollment | 32 |
Est. completion date | October 23, 2017 |
Est. primary completion date | October 23, 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | Davita Clinical Research | Lakewood | Colorado |
United States | Davita Clinical Research | Minneapolis | Minnesota |
United States | Orlando Clinical Research Center | Orlando | Florida |
Lead Sponsor | Collaborator |
---|---|
Bristol-Myers Squibb |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | |
Primary | 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. | |
Primary | 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. | |
Primary | 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 | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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 | |
Primary | 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 | ||
Primary | 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 | ||
Primary | 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 | Pharmacokinetic Parameters of BMS-986177: Cmax | Cmax: Maximum observed plasma concentration | Either Day 1, 5, 8, or 12 depending on the randomization sequence | |
Secondary | Pharmacokinetic Parameters of BMS-986177: Tmax | Time of maximum observed plasma concentration | Either Day 1, 5, 8, or 12 depending on the randomization sequence | |
Secondary | 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 | |
Secondary | Pharmacokinetic Parameters of BMS-986177: fu | Fraction of unbound drug | Either Day 1, 5, 8, or 12 depending on the randomization sequence | |
Secondary | 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 | |
Secondary | 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 | |
Secondary | 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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT03454854 -
Effectiveness of the Application(APP) on Individualized Antithrombotic Therapy
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N/A |