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

• ClinicalTrials.gov Identifier: NCT02034565
• Recruitment Status: Completed
• First Posted: January 13, 2014
• Results First Posted: August 22, 2016
• Last Update Posted: August 22, 2016
• Sponsor: Bristol-Myers Squibb
• Collaborator: Pfizer
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: Apixaban	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Study of Bioavailability of Apixaban Solution Formulation Relative to Apixaban Tablets in Healthy Subjects
• Study Start Date: February 2010
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: March 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment A: Apixaban tablet; Apixaban Film coated Tablet Single dose 10 mg orally	Drug: Apixaban; Other Name: BMS - 562247
Experimental: Treatment B: Apixaban oral solution; Apixaban Solution Single dose 10 mg orally	Drug: Apixaban; Other Name: BMS - 562247

Outcome Measures

Primary Outcome Measures :

1. Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban [ 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 ]
   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)
2. Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban [ 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 ]
   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)
3. 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 [ 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 ]
   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 Outcome Measures :

1. Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs [ Time Frame: 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).
2. Number of Participants With Marked Laboratory Abnormalities [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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)

Contacts and Locations

Locations

United States, New Jersey

Mds Pharma Services

Neptune, New Jersey, United States, 07753

Sponsors and Collaborators

Bristol-Myers Squibb

Pfizer

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

More Information

Additional Information:

BMS clinical trial educational resource 

Investigator Inquiry form 

Publications of Results:

Song Y, Wang X, Perlstein I, Wang J, Badawy S, Frost C, LaCreta F. Relative Bioavailability of Apixaban Solution or Crushed Tablet Formulations Administered by Mouth or Nasogastric Tube in Healthy Subjects. Clin Ther. 2015 Aug;37(8):1703-12. doi: 10.1016/j.clinthera.2015.05.497. Epub 2015 Jul 15.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02034565
• Other Study ID Numbers: CV185-029
• First Posted: January 13, 2014
• Results First Posted: August 22, 2016
• Last Update Posted: August 22, 2016
• Last Verified: July 2016

Additional relevant MeSH terms:

Apixaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants