Healthy Subjects
Conditions
Brief summary
The purpose of this study is to assess the bioavailability of Apixaban oral solution administered through an Nasogastric Tube (NGT) in the presence of Boost® Plus and Apixaban administered as crushed tablet through a nasogastric tube relative to Apixaban solution administered orally in healthy subjects.
Interventions
DRUGApixaban
DIETARY_SUPPLEMENTBoost Plus
Sponsors
Pfizer
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention | Maximum observed plasma concentration (Cmax) is measured in nanograms per milliliter (ng/mL) |
| Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban | Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention | AUC(INF) is measured in nanogram hours per milliliter (ng\*h/mL) |
| Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban | Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention | AUC(0-T) is measured in nanogram hours per milliliter (ng\*h/mL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Day 1 to 30 days after last dose of study drug | 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. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 |
| Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention | Maximum observed plasma concentration (Cmax) is measured in nanograms per milliliter (ng/mL) |
| Number of Participants With Marked Laboratory Abnormalities | Day 1 to 30 days after last dose of study drug | Marked laboratory abnormalities were defined as laboratory assessments meeting the following investigator-specified criteria: Leukocytes \>1.2\* upper limits of normal (ULN) , Basophils \>3%, Eosinophils \>1.5\*ULN, Blood Urine \>=2, Red Blood Cell (RBC) Urine \>=2, White Blood Cell (WBC) Urine \>=2 |
| Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban | Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention | AUC(INF) is measured in nanogram hours per milliliter (ng\*h/mL) |
| Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban | Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention | AUC(0-T) is measured in nanogram hours per milliliter (ng\*h/mL) |
Countries
United States
Participant flow
Pre-assignment details
37 participants were enrolled; 21 were randomized and treated. Reasons for non-randomization include 11 no longer met study criteria, 1 withdrew consent and 4 for other, not specified reasons. 20 participants completed the study; 1 withdrew consent on day 4 of treatment.
Participants by arm
| Arm | Count |
|---|---|
| All Treatment Groups All Randomized Participants | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | All Treatment Groups |
|---|---|
| Age, Continuous | 36.7 years |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 20 | 3 / 20 | 1 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 1 / 21 |
Outcome results
Primary
Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban
AUC(INF) is measured in nanogram hours per milliliter (ng\*h/mL)
Time frame: Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention
Population: All randomized participants with available PK data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban | 1397.666 ng*h/mL |
| Treatment B | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban | 1136.380 ng*h/mL |
90% CI: [0.766, 0.863]
Primary
Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban
AUC(0-T) is measured in nanogram hours per milliliter (ng\*h/mL)
Time frame: Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention
Population: All randomized participants with available PK data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban | 1372.836 ng*h/mL |
| Treatment B | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban | 1112.493 ng*h/mL |
90% CI: [0.764, 0.86]
Primary
Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban
Maximum observed plasma concentration (Cmax) is measured in nanograms per milliliter (ng/mL)
Time frame: Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention
Population: All randomized participants with available pharmacokinetic (PK) data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | 179.116 ng/mL |
| Treatment B | Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | 122.145 ng/mL |
90% CI: [0.621, 0.748]
Secondary
Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban
AUC(INF) is measured in nanogram hours per milliliter (ng\*h/mL)
Time frame: Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention
Population: All randomized participants with available PK data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban | 1397.666 ng*h/mL |
| Treatment B | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban | 1327.248 ng*h/mL |
90% CI: [0.905, 0.997]
Secondary
Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban
AUC(0-T) is measured in nanogram hours per milliliter (ng\*h/mL)
Time frame: Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention
Population: All randomized participants with available PK data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban | 1372.836 ng*h/mL |
| Treatment B | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban | 1300.728 ng*h/mL |
90% CI: [0.903, 0.994]
Secondary
Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban
Maximum observed plasma concentration (Cmax) is measured in nanograms per milliliter (ng/mL)
Time frame: Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose for each intervention
Population: All randomized participants with available PK data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | 179.116 ng/mL |
| Treatment B | Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | 158.371 ng/mL |
90% CI: [0.83, 0.942]
Secondary
Number of Participants With Marked Laboratory Abnormalities
Marked laboratory abnormalities were defined as laboratory assessments meeting the following investigator-specified criteria: Leukocytes \>1.2\* upper limits of normal (ULN) , Basophils \>3%, Eosinophils \>1.5\*ULN, Blood Urine \>=2, Red Blood Cell (RBC) Urine \>=2, White Blood Cell (WBC) Urine \>=2
Time frame: Day 1 to 30 days after last dose of study drug
Population: All randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With Marked Laboratory Abnormalities | Leukocytes | 0 participants |
| Treatment A | Number of Participants With Marked Laboratory Abnormalities | Basophils | 1 participants |
| Treatment A | Number of Participants With Marked Laboratory Abnormalities | Eosinophils | 0 participants |
| Treatment A | Number of Participants With Marked Laboratory Abnormalities | Blood, Urine | 1 participants |
| Treatment A | Number of Participants With Marked Laboratory Abnormalities | RBC, Urine | 0 participants |
| Treatment A | Number of Participants With Marked Laboratory Abnormalities | WBC, Urine | 0 participants |
| Treatment B | Number of Participants With Marked Laboratory Abnormalities | WBC, Urine | 2 participants |
| Treatment B | Number of Participants With Marked Laboratory Abnormalities | Leukocytes | 1 participants |
| Treatment B | Number of Participants With Marked Laboratory Abnormalities | Blood, Urine | 1 participants |
| Treatment B | Number of Participants With Marked Laboratory Abnormalities | RBC, Urine | 2 participants |
| Treatment B | Number of Participants With Marked Laboratory Abnormalities | Basophils | 0 participants |
| Treatment B | Number of Participants With Marked Laboratory Abnormalities | Eosinophils | 1 participants |
| Treatment C | Number of Participants With Marked Laboratory Abnormalities | Basophils | 0 participants |
| Treatment C | Number of Participants With Marked Laboratory Abnormalities | Eosinophils | 0 participants |
| Treatment C | Number of Participants With Marked Laboratory Abnormalities | WBC, Urine | 1 participants |
| Treatment C | Number of Participants With Marked Laboratory Abnormalities | Blood, Urine | 0 participants |
| Treatment C | Number of Participants With Marked Laboratory Abnormalities | Leukocytes | 0 participants |
| Treatment C | Number of Participants With Marked Laboratory Abnormalities | RBC, Urine | 1 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs
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. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
Time frame: Day 1 to 30 days after last dose of study drug
Population: All randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related Deaths | 0 participants |
| Treatment A | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Deaths | 0 participants |
| Treatment A | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | SAE | 0 participants |
| Treatment A | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related AE | 0 participants |
| Treatment A | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Discontinuation of Study Drug Due to AEs | 0 participants |
| Treatment B | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Deaths | 0 participants |
| Treatment B | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | SAE | 0 participants |
| Treatment B | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related AE | 1 participants |
| Treatment B | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related Deaths | 0 participants |
| Treatment B | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Discontinuation of Study Drug Due to AEs | 0 participants |
| Treatment C | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Discontinuation of Study Drug Due to AEs | 0 participants |
| Treatment C | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related Deaths | 0 participants |
| Treatment C | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | SAE | 1 participants |
| Treatment C | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Deaths | 0 participants |
| Treatment C | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related AE | 1 participants |