A Study to Assess Safety and Tolerability of Single Oral Doses of BMS-986177 in Patients With ESRD Treated With Chronic Hemodialysis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- The Number of Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Discontinuation and Death
研究概览
简要总结
To investigate safety of Single Doses of BMS-986177 in Patients with End Stage Renal Disease treated with hemodialysis
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Dose Sequence 1
UFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin
干预措施: Enoxaparin (Drug)
Dose Sequence 1
UFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin
干预措施: unfractionated heparin (UFH) (Drug)
Dose Sequence 1
UFH, BMS-986177 - dose 1, BMS-986177 - dose 2, Enoxaparin
干预措施: BMS-986177 (Drug)
Dose Sequence 2
BMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2
干预措施: Enoxaparin (Drug)
Dose Sequence 2
BMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2
干预措施: unfractionated heparin (UFH) (Drug)
Dose Sequence 2
BMS-986177 - dose 1, Enoxaparin, UFH, BMS-986177 - dose 2
干预措施: BMS-986177 (Drug)
Dose Sequence 3
BMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1
干预措施: Enoxaparin (Drug)
Dose Sequence 3
BMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1
干预措施: unfractionated heparin (UFH) (Drug)
Dose Sequence 3
BMS-986177 - dose 2, UFH, Enoxaparin, BMS-986177 - dose 1
干预措施: BMS-986177 (Drug)
Dose Sequence 4
Enoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH
干预措施: Enoxaparin (Drug)
Dose Sequence 4
Enoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH
干预措施: unfractionated heparin (UFH) (Drug)
Dose Sequence 4
Enoxaparin, BMS-986177 - dose 2, BMS-986177 - dose 1, UFH
干预措施: BMS-986177 (Drug)
结局指标
主要结局
The Number of Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Discontinuation and Death
时间窗: 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 Marked Abnormalities in Clinical Laboratory Tests (Cont.) : Liver and Kidney Function
时间窗: 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 Participants Marked Abnormalities in Clinical Laboratory Tests : Hematology I; Hematology II; Coagulation
时间窗: 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.): Electrolytes
时间窗: 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.): Other Chemistry Testing
时间窗: 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.): Electrolytes (Cont.)
时间窗: 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 Change From Baseline in Vital Signs: Systolic Blood Pressure (mm Hg)
时间窗: Days -3 to -1, 1, 5, 8, 12 and at study discharge on day 13 to day 15
The Number of Marked Abnormalities in Clinical Laboratory Tests (Cont.) : Urinalysis I, Special Studies
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: Days -3 to -1, 1, 5, 8, 12 and at study discharge on day 13 to day 15
次要结局
- 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: 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: Cmaxfu(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(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)(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)