Trial Outcomes & Findings for Phase 1 Bioavailability Study of Apixaban Solution Formulation Relative to Apixaban Tablets in Healthy Subjects (NCT NCT02034565)

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

48 participants

Primary outcome timeframe

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

Results posted on

2016-08-22

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Treatment A, Then Treatment B Each participant was given two interventions, one per period, with a 4 day washout in between periods. Treatment A: Single dose apixaban film-coated tablet, 10 milligrams (mg) via 2 x 5 mg tablets, administered orally Treatment B: Single dose apixaban solution, 10 milligrams (mg) via 25 milliliters (mL) x 0.4 mg/mL, administered orally	Treatment B, Then Treatment A Each participant was given two interventions, one per period, with a 4 day washout in between periods. Treatment A: Single dose apixaban film-coated tablet, 10 milligrams (mg) via 2 x 5 mg tablets, administered orally Treatment B: Single dose apixaban solution, 10 milligrams (mg) via 25 milliliters (mL) x 0.4 mg/mL, administered orally
Overall Study STARTED	7	7
Overall Study COMPLETED	6	7
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment A, Then Treatment B Each participant was given two interventions, one per period, with a 4 day washout in between periods. Treatment A: Single dose apixaban film-coated tablet, 10 milligrams (mg) via 2 x 5 mg tablets, administered orally Treatment B: Single dose apixaban solution, 10 milligrams (mg) via 25 milliliters (mL) x 0.4 mg/mL, administered orally	Treatment B, Then Treatment A Each participant was given two interventions, one per period, with a 4 day washout in between periods. Treatment A: Single dose apixaban film-coated tablet, 10 milligrams (mg) via 2 x 5 mg tablets, administered orally Treatment B: Single dose apixaban solution, 10 milligrams (mg) via 25 milliliters (mL) x 0.4 mg/mL, administered orally
Overall Study Adverse Event	1	0

Baseline Characteristics

Phase 1 Bioavailability Study of Apixaban Solution Formulation Relative to Apixaban Tablets in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Treatment Groups n=14 Participants All Randomized Participants
Age, Continuous	36 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Treatment A: Apixaban Tablet n=14 Participants Single dose apixaban 10 mg (film-coated tablet) administered orally	Treatment B: Apixaban Oral Solution n=13 Participants Single dose apixaban 10 mg (solution) administered orally
Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban	293.994 ng/mL Interval 245.998 to 351.354	287.164 ng/mL Interval 242.331 to 340.291

PRIMARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Treatment A: Apixaban Tablet n=13 Participants Single dose apixaban 10 mg (film-coated tablet) administered orally	Treatment B: Apixaban Oral Solution n=13 Participants Single dose apixaban 10 mg (solution) administered orally
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 Interval 2414.339 to 3047.432	2848.968 ng*h/mL Interval 2557.946 to 3173.101

PRIMARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Treatment A: Apixaban Tablet n=13 Participants Single dose apixaban 10 mg (film-coated tablet) administered orally	Treatment B: Apixaban Oral Solution n=13 Participants Single dose apixaban 10 mg (solution) administered orally
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 Interval 2372.198 to 3001.385	2784.366 ng*h/mL Interval 2497.506 to 3104.175

SECONDARY outcome

Timeframe: Day 1 to 30 days after last dose of study drug

Population: All treated participants

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).

Outcome measures

Outcome measures
Measure	Treatment A: Apixaban Tablet n=14 Participants Single dose apixaban 10 mg (film-coated tablet) administered orally	Treatment B: Apixaban Oral Solution n=13 Participants Single dose apixaban 10 mg (solution) administered orally
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	0 participants
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	1 participants
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	0 participants
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	0 participants
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	0 participants

SECONDARY outcome

Timeframe: Pre-study screen (Day -1) to Day 8 or day of study discharge

Population: All treated participants

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.

Outcome measures

Outcome measures
Measure	Treatment A: Apixaban Tablet n=14 Participants Single dose apixaban 10 mg (film-coated tablet) administered orally	Treatment B: Apixaban Oral Solution n=13 Participants Single dose apixaban 10 mg (solution) administered orally
Number of Participants With Marked Laboratory Abnormalities Leukocytes, Low	1 participants	1 participants
Number of Participants With Marked Laboratory Abnormalities Absolute Neutrophils + Bands, Low	1 participants	1 participants
Number of Participants With Marked Laboratory Abnormalities WBC, Urine, High	0 participants	1 participants

Adverse Events

Arm A: Apixaban Tablet

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Arm B: Apixaban Oral Solution

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Arm A: Apixaban Tablet n=14 participants at risk Single dose apixaban 10 mg (film-coated tablet) administered orally	Arm B: Apixaban Oral Solution n=13 participants at risk Single dose apixaban 10 mg (solution) administered orally
Gastrointestinal disorders Constipation	7.1% 1/14 • From first dose to last dose plus 30 days	0.00% 0/13 • From first dose to last dose plus 30 days
Nervous system disorders Headache	14.3% 2/14 • From first dose to last dose plus 30 days	7.7% 1/13 • From first dose to last dose plus 30 days
Gastrointestinal disorders Toothache	7.1% 1/14 • From first dose to last dose plus 30 days	0.00% 0/13 • From first dose to last dose plus 30 days
General disorders Vessel puncture site haematoma	7.1% 1/14 • From first dose to last dose plus 30 days	0.00% 0/13 • From first dose to last dose plus 30 days
General disorders Fatigue	7.1% 1/14 • From first dose to last dose plus 30 days	0.00% 0/13 • From first dose to last dose plus 30 days
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/14 • From first dose to last dose plus 30 days	7.7% 1/13 • From first dose to last dose plus 30 days
Gastrointestinal disorders Dyspepsia	7.1% 1/14 • From first dose to last dose plus 30 days	0.00% 0/13 • From first dose to last dose plus 30 days
Gastrointestinal disorders Eructation	7.1% 1/14 • From first dose to last dose plus 30 days	0.00% 0/13 • From first dose to last dose plus 30 days

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60