Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to assess the oral bioavailability of Apixaban solution formulation (Treatment B, 10 mg as 25 mL x 0.4 mg/mL) relative to Apixaban tablets (Treatment A, 10 mg as 2 x 5 mg tablets) in healthy subjects.
Interventions
DRUGApixaban
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 or relevant trauma (e.g., history of chronic hypertension, bacterial endocarditis, hemorrhagic stroke, motor vehicle accident resulting in significant head trauma or internal injuries) * History or evidence of abnormal bleeding or coagulation disorder (e.g., easy bruising or gingival bleeding, prolonged bleeding after dental extraction, postpartum, or after trauma, wounds or surgery)
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 per intervention | Serial blood samples for pharmacokinetic analysis were collected at selected times up to 72 hours after each dose. 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 per intervention | Serial blood samples for pharmacokinetic analysis were collected at selected times up to 72 hours after each dose. 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 per intervention | Serial blood samples for pharmacokinetic analysis were collected at selected times up to 72 hours after each dose. 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 Adverse Events (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, v13). |
| Number of Participants With Marked Laboratory Abnormalities | Pre-study screen (Day -1) to Day 8 or day of study discharge | Clinical laboratory tests were performed pre-study and at selected times throughout the study. Marked laboratory abnormalities were defined as laboratory assessments meeting the following investigator-specified criteria: Leukocytes \< 0.9\* lower limits of normal (LLN), absolute neutrophils + bands \<= 1.500 10\*3 cells/microliter, white blood cells (WBC) urine value \>= 2+. These laboratory abnormalities were not considered clinically significant and therefore not adverse events. |
Countries
United States
Participant flow
Pre-assignment details
48 participants were enrolled; 14 were randomized and treated. Reasons for non-randomization include 23 no longer met study criteria, 4 withdrew consent, 6 due to study being full, and 1 completed an alternate treatment. 13 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| All Treatment Groups All Randomized Participants | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | All Treatment Groups |
|---|---|
| Age, Continuous | 36 years |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 14 | 2 / 13 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 |
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
Serial blood samples for pharmacokinetic analysis were collected at selected times up to 72 hours after each dose. 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 per intervention
Population: All treated participants with available pk data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A: Apixaban Tablet | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban | 2712.477 ng*h/mL |
| Treatment B: Apixaban Oral Solution | Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban | 2848.968 ng*h/mL |
90% CI: [0.938, 1.176]
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
Serial blood samples for pharmacokinetic analysis were collected at selected times up to 72 hours after each dose. 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 per intervention
Population: All treated participants with available pk data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A: Apixaban Tablet | 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 | 2668.310 ng*h/mL |
| Treatment B: Apixaban Oral Solution | 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 | 2784.366 ng*h/mL |
90% CI: [0.933, 1.167]
Primary
Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban
Serial blood samples for pharmacokinetic analysis were collected at selected times up to 72 hours after each dose. 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 per intervention
Population: All treated participants with available pharmacokinetic (pk) data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A: Apixaban Tablet | Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | 293.994 ng/mL |
| Treatment B: Apixaban Oral Solution | Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | 287.164 ng/mL |
90% CI: [0.756, 1.261]
Secondary
Number of Participants With Marked Laboratory Abnormalities
Clinical laboratory tests were performed pre-study and at selected times throughout the study. Marked laboratory abnormalities were defined as laboratory assessments meeting the following investigator-specified criteria: Leukocytes \< 0.9\* lower limits of normal (LLN), absolute neutrophils + bands \<= 1.500 10\*3 cells/microliter, white blood cells (WBC) urine value \>= 2+. These laboratory abnormalities were not considered clinically significant and therefore not adverse events.
Time frame: Pre-study screen (Day -1) to Day 8 or day of study discharge
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Apixaban Tablet | Number of Participants With Marked Laboratory Abnormalities | Leukocytes, Low | 1 participants |
| Treatment A: Apixaban Tablet | Number of Participants With Marked Laboratory Abnormalities | Absolute Neutrophils + Bands, Low | 1 participants |
| Treatment A: Apixaban Tablet | Number of Participants With Marked Laboratory Abnormalities | WBC, Urine, High | 0 participants |
| Treatment B: Apixaban Oral Solution | Number of Participants With Marked Laboratory Abnormalities | Leukocytes, Low | 1 participants |
| Treatment B: Apixaban Oral Solution | Number of Participants With Marked Laboratory Abnormalities | Absolute Neutrophils + Bands, Low | 1 participants |
| Treatment B: Apixaban Oral Solution | Number of Participants With Marked Laboratory Abnormalities | WBC, Urine, High | 1 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (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, v13).
Time frame: Day 1 to 30 days after last dose of study drug
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Apixaban Tablet | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related AE | 0 participants |
| Treatment A: Apixaban Tablet | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related Deaths | 0 participants |
| Treatment A: Apixaban Tablet | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | Deaths | 0 participants |
| Treatment A: Apixaban Tablet | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | Discontinuation of Study Drug Due to AEs | 1 participants |
| Treatment A: Apixaban Tablet | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | SAE | 0 participants |
| Treatment B: Apixaban Oral Solution | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | Discontinuation of Study Drug Due to AEs | 0 participants |
| Treatment B: Apixaban Oral Solution | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | SAE | 0 participants |
| Treatment B: Apixaban Oral Solution | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related AE | 1 participants |
| Treatment B: Apixaban Oral Solution | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | Deaths | 0 participants |
| Treatment B: Apixaban Oral Solution | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | Treatment-Related Deaths | 0 participants |