Phase 1 Oral Solution Bioavailability Study of Apixaban When Administered Through a Nasogastric Tube in Healthy Subjects
- Registration Number
- NCT02034578
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to assess the bioavailability of Apixaban solution administered through NGT and washed with Dextrose 5% in water (D5W) or infant formula relative to Apixaban solution administered orally in healthy subjects
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
- Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
- Any significant acute or chronic medical illness
- Any history or evidence of abnormal bleeding or coagulation disorders, intracranial hemorrhage, or abnormal bleeding (including heavy menstrual bleeding that has resulted in anemia within the past 1 year) or coagulation disorders in a first degree relative
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Arm A: Apixaban Apixaban Single dose Apixaban 5 mg (0.4 mg/mL x 12.5 mL) oral solution via oral syringe Arm B: Apixaban Apixaban Single dose Apixaban 5 mg (0.4 mg/mL x 12.5 mL) oral solution via nasogastric tube (NGT) immediately followed by 60 mL of D5W via NGT Arm C: Apixaban Apixaban Single dose Apixaban 5 mg (0.4 mg/mL x 12.5 mL) oral solution via NGT immediately followed by 60 mL of infant formula via NGT
- Primary Outcome Measures
Name Time Method Adjusted Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Apixaban Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 Samples of plasma from participants were obtained at the following times: 0 hour (h) and post dose at 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h. Apixaban was assayed using a validated Liquid chromatography tandem mass spectrometry (LC-MS/MS) method during the period of known analyte stability. Maximum observed plasma concentration (Cmax) was measured in nanograms per milliliter (ng/mL).
- Secondary Outcome Measures
Name Time Method Median Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 Samples of plasma from participants were obtained at the following times: 0 hour (h), 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. Maximum observed plasma concentration (Tmax) was measured in hours (h).
Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings Screening, Day 1 of Periods, 1, 2, and 3, and Day 4 of Period 3 12-lead electrocardiograms (ECGs) and Vital Signs were performed at Screening, and Day 1 of Periods 1, 2 and 3 (pre-dose and prior to NGT placement, if done). Vital signs and ECGs were also performed on Day 4 of Period 3, prior to discharge from the study. Vital signs included body temperature, respiratory rate, seated blood pressure and heart rate. Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes. Participants had physical examinations on Period 1, Day 1 (pre-dose) and Day 4 of Period 3, prior to study discharge.
Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration, AUC(0-T), of Apixaban Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. AUC(0-T) was measured in nanograms\*hours per milliliter (ng\*h/mL).
Mean Plasma Elimination Half-Life (T-HALF) of Apixaban Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. T-HALF was measured in hours (h).
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death Day 1 to Day 12 AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time, AUC(INF), of Apixaban Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. AUC(0-INF) was measured in ng\*h/mL.
Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests Screening, Day -1, Day 4 of Periods, 1, 2, and 3 Participants were required to fast for at least 10 hours prior to the collection of specimens for clinical laboratory tests. Tests were performed at Screening, Day -1, and Day 4 of each period 1 - 3. Leukocyte criteria: Lower limits of normal (LLN), upper limits of normal (ULN), pre-treatment (preRX). Low Leukocytes: if value \< 0.9\*LLN, or if preRX \< LLN then use \< 0.85\* preRX. High lymphocytes: if value \> 7.500 10\^3 cells/ µL. Low neutrophils plus bands: if value \<= 1.500 10\^3 cells/µL. High creatine kinase: if value \> 1.5\* ULN. Blood in urine: if value \>= 2 plus, or if preRX \>= 1 plus then use \>= 2\*preRX.
Trial Locations
- Locations (1)
Parexel Baltimore Early Phase Clinical Unit
🇺🇸Baltimore, Maryland, United States