ThrombosisPhase 1NCT02101112

Bioavailability of Apixaban Crushed Tablet

A Phase 1 study testing Apixaban in people with Thrombosis, run by Bristol-Myers Squibb.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to determine whether the bioavailability of apixaban crushed tablets suspended in water or mixed with applesauce is similar to the bioavailability of apixaban whole tablets administered orally. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Thrombosis
What is being tested?: Apixaban
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 69 participants
Where: No sites listed yet
Study dates: Mar 2014to May 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy participants as determined by no clinically significant deviation from normal in findings of medical history, physical examination, electrocardiograms, vital signs, and clinical laboratory tests.
Women of childbearing potential allowed. Must be following highly effective methods of contraception

Who cannot join

Any significant acute or chronic medical illness
History of significant head injury within the last 2 years, including individuals with base of skull fractures
Any major surgery within 4 weeks of study drug administration or anticipated within 2 weeks after completion of the study
Any gastrointestinal (GI) surgery or GI disease that could impact absorption of study drug
History of Gilbert's Syndrome
Inability to tolerate oral medication

Show all 18Show fewer

Inability to be venipunctured and/or tolerate venous access
Use of tobacco- or nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to study drug administration
Any laboratory test results outside of the range of normal, confirmed by repeat results of:
Platelet count <150,000 cells/µL
Activated partial thromboplastin time >upper limit of normal (ULN)
International normalized ratio >ULN
Alanine aminotransferase >ULN
Aspartate aminotransferase >ULN
Total bilirubin >ULN
Serum creatinine ≥1.5 mg/dL
Hemoglobin <lower limit of normal (LLN)
Hematocrit <LLN

About this study

Official title: Relative Bioavailability of Crushed Apixaban Tablets Administered With Water or Apple Sauce Compared With Intact Tablet in Healthy Subjects

Read the detailed description

This study will investigate the bioavailability of apixaban administered as crushed tablets suspended in water and as crushed tablets mixed with applesauce compared with that of whole tablets. The study results may allow enhancement of the apixaban label to include alternative methods of apixaban administration, which may be of benefit to patients who have difficulty swallowing.

Conditions: Thrombosis
Being tested: Apixaban
Medical subject headings: Thrombosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ApixabanDrug
Also called Eliquis®

Study groups in NCT02101112
Study group	Role	What they receive
Apixaban, 10 mg (whole tablets)	Experimental	Participants received a single dose of apixaban, 10 mg, given orally as 2 5-mg whole commercial tablets (reference) Receives: Drug: Apixaban
Apixaban, 10 mg (crushed and suspended in water)	Experimental	Participants received a single dose of apixaban, 10 mg, given by mouth as 2 5-mg whole commercial tablets crushed and suspended in 30 mL of water Receives: Drug: Apixaban
Apixaban, 10 mg (crushed and mixed with applesauce)	Experimental	Participants received a single dose of 10 mg, given by mouth as 2 5-mg apixaban commercial tablets crushed and mixed with 30 g of applesauce Receives: Drug: Apixaban

What is being measured

The primary outcome is the main question the study is designed to answer.

Adjusted Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Apixaban
Maximum observed plasma concentration (Cmax) measured in nanograms per milliliter (ng/mL)
Measured: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60 and 72 hours post dose
Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban
Area Under the Plasma Concentration-time Curve (AUC) From Time of Zero Extrapolated to Infinite Time (INF) [AUC (INF)] is measured as nanograms multiplied by hours per milliliter (ng*h/mL)
Measured: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 hours post dose
Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Concentration [AUC (0-T)] is measured as nanograms multiplied by hours per milliliter (ng*h/mL)
Measured: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 hours post dose

Secondary outcomes (4)

Number of Participants With Serious Adverse Events, Death, or Discontinuation Due to Adverse Events by Study Completion
Adverse Event (AE) = any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious Adverse Event (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.
Measured: Randomization to May 2014; approximately 6 weeks
Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban
Time of maximum observed plasma concentration (Tmax) measured in hours (h)
Measured: Days 1, 5 and 9 pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12 24, 36, 48, 60 and 72 hrs post dose
Terminal Plasma Half-life (T-HALF) of Apixaban
Terminal plasma half-life (T-HALF) was derived from plasma concentration versus time data. T-HALF was the time required for one half of the total amount of administered drug to be eliminated from the body.
Measured: Days 1, 5 and 9 pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12 24, 36, 48, 60 and 72 hrs post dose
Relative Bioavailability (Frel) of Apixaban
Frel is calculated using the treatment ratio of AUC(INF) where the denominator is the AUC(INF) of the reference therapy, 10mg of Apixaban (whole tablet).
Measured: Days 1, 5 and 9 pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12 24, 36, 48, 60 and 72 hrs post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2014May 2014

First posted1 Apr 2014 (estimated)
Study startMar 2014
Primary completionMay 2014
Study completionMay 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for ThrombosisStudies of the same condition, open and under way.
More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02101112
Sponsor's protocol ID: CV185-292
Status last verified: Feb 2016
First submitted: 28 Mar 2014
Last updated: 3 Mar 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Song Y, Chang M, Suzuki A, Frost RJ, Kelly A, LaCreta F, Frost C. Evaluation of Crushed Tablet for Oral Administration and the Effect of Food on Apixaban Pharmacokinetics in Healthy Adults. Clin Ther. 2016 Jul;38(7):1674-1685.e1. doi: 10.1016/j.clinthera.2016.05.004. Epub 2016 Jun 10.
PubMed 27292282

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Thrombosis trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Relative Bioavailability of Crushed Apixaban Tablets Administered With Water or Apple Sauce Compared With Intact Tablet in Healthy Subjects
ClinicalTrials.gov ID: NCT02101112
Acronym / sponsor ID: CV185-292
Conditions: Thrombosis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 69 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Study start: Mar 2014
Primary completion: May 2014 (actual)
Study completion: May 2014 (actual)
First posted: 1 Apr 2014 (estimated)
Results: Posted 3 Mar 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Apixaban, 10 mg (whole tablets)	Experimental	Drug: ApixabanParticipants received a single dose of apixaban, 10 mg, given orally as 2 5-mg whole commercial tablets (reference)
Apixaban, 10 mg (crushed and suspended in water)	Experimental	Drug: ApixabanParticipants received a single dose of apixaban, 10 mg, given by mouth as 2 5-mg whole commercial tablets crushed and suspended in 30 mL of water
Apixaban, 10 mg (crushed and mixed with applesauce)	Experimental	Drug: ApixabanParticipants received a single dose of 10 mg, given by mouth as 2 5-mg apixaban commercial tablets crushed and mixed with 30 g of applesauce

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (2 listed)

Healthy participants as determined by no clinically significant deviation from normal in findings of medical history, physical examination, electrocardiograms, vital signs, and clinical laboratory tests.
Women of childbearing potential allowed. Must be following highly effective methods of contraception

Key exclusion criteria (18 listed)

Any significant acute or chronic medical illness
History of significant head injury within the last 2 years, including individuals with base of skull fractures
Any major surgery within 4 weeks of study drug administration or anticipated within 2 weeks after completion of the study
Any gastrointestinal (GI) surgery or GI disease that could impact absorption of study drug
History of Gilbert's Syndrome

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ApixabanAlso: Eliquis®	Drug	Apixaban, 10 mg (crushed and mixed with applesauce), Apixaban, 10 mg (crushed and suspended in water), Apixaban, 10 mg (whole tablets)

Primary outcome

Adjusted Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Apixaban
Time frame: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60 and 72 hours post dose
Maximum observed plasma concentration (Cmax) measured in nanograms per milliliter (ng/mL)
Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban
Time frame: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 hours post dose
Area Under the Plasma Concentration-time Curve (AUC) From Time of Zero Extrapolated to Infinite Time (INF) [AUC (INF)] is measured as nanograms multiplied by hours per milliliter (ng*h/mL)
Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban
Time frame: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 hours post dose
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Concentration [AUC (0-T)] is measured as nanograms multiplied by hours per milliliter (ng*h/mL)

4 secondary outcomes

Number of Participants With Serious Adverse Events, Death, or Discontinuation Due to Adverse Events by Study Completion
Time frame: Randomization to May 2014; approximately 6 weeks
Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban
Time frame: Days 1, 5 and 9 pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12 24, 36, 48, 60 and 72 hrs post dose
Terminal Plasma Half-life (T-HALF) of Apixaban
Time frame: Days 1, 5 and 9 pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12 24, 36, 48, 60 and 72 hrs post dose
Relative Bioavailability (Frel) of Apixaban
Time frame: Days 1, 5 and 9 pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12 24, 36, 48, 60 and 72 hrs post dose

Results and safety

Results posted to the registry on 3 Mar 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment A Then Treatment B Then Treatment C	6	6
Treatment A Then Treatment C Then Treatment B	5	5
Treatment B Then Treatment C Then Treatment A	6	5
Treatment B Then Treatment A Then Treatment C	5	5
Treatment C Then Treatment A Then Treatment B	6	5
Treatment C Then Treatment B Then Treatment A	5	5

Primary outcome: Adjusted Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Apixaban

Time frame: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60 and 72 hours post dose. Geometric mean (90% Confidence Interval). Unit: ng/mL

Measure	Apixaban, 10 mg (Whole Tablets) n = 32	Apixaban, 10 mg (Crushed and Suspended in Water) n = 33	Apixaban, 10 mg (Crushed and Mixed With Applesauce) n = 32
Value	236 (217 to 256)	249 (232 to 266)	186 (174 to 199)

Apixaban, 10 mg (Whole Tablets) vs Apixaban, 10 mg (Crushed and Suspended in Water): Ratio of Adjusted Geometric Means: 1.054 (90% CI 0.994 to 1.118)
Apixaban, 10 mg (Whole Tablets) vs Apixaban, 10 mg (Crushed and Mixed With Applesauce): Ratio of Adjusted Geometric Means: 0.788 (90% CI 0.741 to 0.839)

Population analysed: All evaluable pharmacokinetic (PK) participants who were treated with apixaban

Primary outcome: Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban

Time frame: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 hours post dose. Geometric mean (90% Confidence Interval). Unit: ng*h/mL

Measure	Apixaban, 10 mg (Whole Tablets) n = 32	Apixaban, 10 mg (Crushed and Suspended in Water) n = 33	Apixaban, 10 mg (Crushed and Mixed With Applesauce) n = 32
Value	2461 (2273 to 2664)	2528 (2375 to 2692)	2055 (1915 to 2206)

Apixaban, 10 mg (Whole Tablets) vs Apixaban, 10 mg (Crushed and Suspended in Water): Ratio of Adjusted Geometric Means: 1.027 (90% CI 0.981 to 1.076)
Apixaban, 10 mg (Whole Tablets) vs Apixaban, 10 mg (Crushed and Mixed With Applesauce): Ratio of Adjusted Geometric Means: 0.835 (90% CI 0.797 to 0.875)

Population analysed: All evaluable pharmacokinetic (PK) participants who were treated with apixaban

Primary outcome: Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban

Time frame: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 hours post dose. Geometric mean (90% Confidence Interval). Unit: ng*h/mL

Measure	Apixaban, 10 mg (Whole Tablets) n = 32	Apixaban, 10 mg (Crushed and Suspended in Water) n = 33	Apixaban, 10 mg (Crushed and Mixed With Applesauce) n = 32
Value	2423 (2238 to 2623)	2488 (2336 to 2651)	2015 (1876 to 2165)

Apixaban, 10 mg (Whole Tablets) vs Apixaban, 10 mg (Crushed and Suspended in Water): Ratio of Adjusted Geometric Means: 1.027 (90% CI 0.981 to 1.075)
Apixaban, 10 mg (Whole Tablets) vs Apixaban, 10 mg (Crushed and Mixed With Applesauce): Ratio of Adjusted Geometric Means: 0.832 (90% CI 0.794 to 0.871)

Population analysed: All evaluable pharmacokinetic (PK) participants who were treated with apixaban

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 1 to May 2014; approximately 6 weeks F. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Apixaban, 10 mg (Whole Tablets)	0 of 32 (0%)	0 of 32 (0%)	Not reported
Apixaban, 10 mg (Crushed and Suspended in Water)	0 of 33 (0%)	0 of 33 (0%)	Not reported
Apixaban, 10 mg (Crushed and Mixed With Applesauce)	0 of 32 (0%)	0 of 32 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27292282Song Y, Chang M, Suzuki A, Frost RJ, Kelly A, LaCreta F, Frost C. Evaluation of Crushed Tablet for Oral Administration and the Effect of Food on Apixaban Pharmacokinetics in Healthy Adults. Clin Ther. 2016 Jul;38(7):1674-1685.e1. doi: 10.1016/j.clinthera.2016.05.004. Epub 2016 Jun 10.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bristol-Myers Squibb study director

Bristol-Myers Squibb

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Apixaban in people with Thrombosis, run by Bristol-Myers Squibb.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adjusted Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Apixaban (time frame: Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60 and 72 hours post dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02101112, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2016.