BioequivalencePhase 1NCT02436577

Study to Assess the Bioequivalence Between Ticagrelor Orodispersible Tablets and Ticagrelor Immediate-release Tablets in Japanese Subjects

A Phase 1 study testing Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water, Ticagrelor OD tablet (90 mg single dose) administered without water and Ticagrelor IR tablet (90 mg) administered with 150 mL of water in people with Bioequivalence and Healthy Japanese Subjects, run by AstraZeneca at 1 site in United Kingdom.

Completed

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

Official record

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Trial summary

This study will be an open-label, randomised, three-period, three-treatment, crossover study in healthy Japanese male and female of non-childbearing potential subjects, performed at a single study centre. Read more about this study

Who is it for?: Ages 20 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Bioequivalence, Healthy Japanese Subjects, Pharmacokinetics
What is being tested?: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water, Ticagrelor OD tablet (90 mg single dose) administered without water and Ticagrelor IR tablet (90 mg) administered with 150 mL of water
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: 1 siteUnited Kingdom
Study dates: Jun 2015to Aug 2015
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 20 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male and female subjects aged 20 to 45 years with suitable veins for cannulation or repeated venepuncture.
Be Japanese. Japanese is defined as having both parents and four grandparents who are Japanese. This includes second and third generation Japanese whose parents or grandparents are living in a country other than Japan.
Females must have a negative pregnancy test at screening and on each admission to the clinical unit, must not be lactating, and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
Have a body mass index (BMI) between 18.0 and 27.0 kg/m2 inclusive and weigh at least 45 kg and no more than 85 kg inclusive.

Show all 14Show fewer

Be able and willing to communicate with the investigator and comply with all study procedures, including reproductive restrictions.
Exclusion Criteria: - History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influences the results or the potential subject's ability to participate in the study.
Current smokers or those who have smoked or used nicotine products within the previous 3 months.
History of hemophilia, von Willebrand's disease, lupus anticoagulant, or other diseases/syndromes that can either alter or increase the propensity for bleeding.
A personal history of vascular abnormalities including aneurysms; a personal history of severe hemorrhage, hematemesis, melena, hemoptysis, severe epistaxis, severe thrombocytopenia, intracranial hemorrhage; or rectal bleeding within 1 year prior to screening; or history suggestive of peptic ulcer disease; or at the discretion of the investigator.
History of a clinically significant non-traumatic bleed or clinically significant bleeding risk, as judged by the investigator.
Use of aspirin, ibuprofen, non-steroidal anti-inflammatory drugs (NSAIDs), or any other drug known to increase the propensity for bleeding for 2 weeks before randomization.
Platelet count less than 150 x 10^9/L.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Research Site
Harrow

Other trials in United Kingdom

About this study

Official title: An Open-label, Randomized, Three-period, Three-treatment, Crossover, Single-centre, Single-dose Study to Assess the Bioequivalence Between Ticagrelor Orodispersible Tablets and Ticagrelor Immediate-release Tablets in Healthy Japanese Subjects.

The objective of the study is to assess the bioequivalence of ticagrelor orodispersible (OD) tablets when administered with water and without water and ticagrelor immediate-release (IR) tablets.

Read the detailed description

Study to evaluate the bioequivalence of ticagrelor orodispersible (OD) tablets administered with water and without water and ticagrelor immediate-release (IR) tablets.

Conditions: Bioequivalence, Healthy Japanese Subjects, Pharmacokinetics
Being tested: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water, Ticagrelor OD tablet (90 mg single dose) administered without water, Ticagrelor IR tablet (90 mg) administered with 150 mL of water
Keywords: ticagrelor orodispersible tablet, ticagrelor immediate-release tablet, bioequivalence, Phase I, healthy Japanese subjects

What participants receive

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

Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of waterDrug
Also called Treatment A
Ticagrelor 90 mg OD tablet, single dose
Ticagrelor OD tablet (90 mg single dose) administered without waterDrug
Also called Treatment B
Ticagrelor 90 mg OD tablet, single dose
Ticagrelor IR tablet (90 mg) administered with 150 mL of waterDrug
Also called Treatment C
Ticagrelor 90 mg IR tablet, single dose

Study groups in NCT02436577
Study group	Role	What they receive
Sequence ABC	Experimental	Treatment A in Period 1, Treatment B in Period 2 and Treatment C in Period 3 Receives: Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without water; Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water
Sequence BCA	Experimental	Treatment B in Period 1, Treatment C in Period 2 and Treatment A in Period 3 Receives: Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without water; Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water
Sequence CAB	Experimental	Treatment C in Period 1, Treatment A in Period 2 and Treatment B in Period 3 Receives: Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without water; Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water
Sequence ACB	Experimental	Treatment A in Period 1, Treatment C in Period 2 and Treatment B in Period 3 Receives: Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without water; Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water
Sequence BAC	Experimental	Treatment B in Period 1, Treatment A in Period 2 and Treatment C in Period 3 Receives: Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without water; Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water
Sequence CBA	Experimental	Treatment C in Period 1, Treatment B in Period 2 and Treatment A in Period 3 Receives: Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without water; Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water

What is being measured

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

Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Comparison of Cmax (maximum observed plasma concentration) of ticagrelor and its active metabolite AR-C124910XX following single doses of the orodispersible (OD) tablet - when administered with and without water - and ticagrelor immediate-release (IR) tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte Concentration AUC (0-t) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Comparison of AUC(0-t) (Area under the plasma concentration-time curve from time zero to time of last quantifiable analyte concentration) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Comparison of AUC (Area under plasma concentration-time curve from zero to infinity) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.

Secondary outcomes (13)

Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Comparison of tmax (Time to reach maximum observed concentration) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Comparison of t½λz (half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Terminal Elimination Rate Constant (λz) of Ticagrelor and Its Active Metabolite, AR-C124910XX.
Comparison of terminal elimination rate constant (λz) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Mean Residence Time (MRT) of Ticagrelor and Its Active Metabolite AR-C124910XX
Comparison of MRT (mean residence time) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
MRCmax (Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights) of Active Metabolite AR-C124910XX
Assessment of MRCmax (ratio of metabolite Cmax to parent Cmax, adjusted for differences in molecular weights) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Ratio of Metabolite AUC(0-t) to Parent AUC(0-t), Adjusted for Differences in Molecular Weights (MRAUC [0-t]) of Active Metabolite AR-C124910XX
Assessment of MRAUC(0-t) (Ratio of metabolite AUC(0-t) to parent AUC(0-t), adjusted for differences in molecular weights) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Ratio of Metabolite AUC to Parent AUC, Adjusted for Differences in Molecular Weights (MRAUC) of Active Metabolite AR-C124910XX
Assessment of MRAUC (Ratio of metabolite AUC to parent AUC, adjusted for differences in molecular weights) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Number of Participants With Adverse Events (AEs)
An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The term AE is used generally to include any AE whether serious or non-serious. A serious AE (SAE) is an AE that fulfills one or more of the following criteria: results in death, is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above.
Measured: From the date of randomization (Day 1 of the first treatment period) until the final follow-up visit (5 to 10 days after last administration of IMP).
Elimination Rate Constant (Kel) of Ticagrelor and Its Active Metabolite AR-C124910XX
Comparison of kel (elimination rate constant) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Measured: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP)
The following variables were collected after the participants had rested in the supine position for at least 5 minutes: SBP and DBP.
Measured: Day 1 (pre dose, 2 hours, and 4 hours post dose) and Day 2 (24 hours post dose).
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Vital signs i.e. Pulse (beats per minute [bpm]) were collected after the participant has rested in the supine position for at least 5 minutes.
Measured: At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart) and during treatment periods at pre-dose and post-dose at 2, 4 and 24 hours.
Participants With Significant Findings in 12-Lead Electrocardiography (ECG).
A 12-lead ECG was obtained after the participant rested in supine position for at least 10 minutes. The study physician was to judge the overall interpretation as normal or abnormal. If abnormal, it was decided as to whether or not the abnormality was clinically significant and the reason for the abnormality was recorded.
Measured: At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart).
Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis.
Participants were assessed through each laboratory variables for any significant abnormalities. Hematology assessments included white blood cell count, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and others. Clinical chemistry assessment included testing levels of sodium, potassium, urea, creatinine, albumin, calcium, glucose (fasting) and others. Urinalysis assessment included glucose, protein, blood and microscopy (if positive for blood or protein).
Measured: At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart).

Timeline

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

Jun 2015Aug 2015

First posted7 May 2015 (estimated)
Study startJun 2015
Primary completionAug 2015
Study completionAug 2015

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.
Other trials for BioequivalenceStudies of the same condition, open and under way.
More trials run by AstraZenecaThe 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
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02436577
Sponsor's protocol ID: D5139C00004
Status last verified: Nov 2016
First submitted: 7 Apr 2015
Last updated: 11 Jan 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Randomized, Three-period, Three-treatment, Crossover, Single-centre, Single-dose Study to Assess the Bioequivalence Between Ticagrelor Orodispersible Tablets and Ticagrelor Immediate-release Tablets in Healthy Japanese Subjects.
ClinicalTrials.gov ID: NCT02436577
Acronym / sponsor ID: D5139C00004
Conditions: Bioequivalence, Healthy Japanese Subjects, Pharmacokinetics
Keywords: ticagrelor orodispersible tablet, ticagrelor immediate-release tablet, bioequivalence, Phase I, healthy Japanese subjects
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 51 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Jun 2015
Primary completion: Aug 2015 (actual)
Study completion: Aug 2015 (actual)
First posted: 7 May 2015 (estimated)
Results: Posted 11 Jan 2017

Clinical summary

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

The objective of the study is to assess the bioequivalence of ticagrelor orodispersible (OD) tablets when administered with water and without water and ticagrelor immediate-release (IR) tablets.

Detailed description

Study to evaluate the bioequivalence of ticagrelor orodispersible (OD) tablets administered with water and without water and ticagrelor immediate-release (IR) tablets.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Sequence ABC	Experimental	Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water, Drug: Ticagrelor OD tablet (90 mg single dose) administered without water, Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of waterTreatment A in Period 1, Treatment B in Period 2 and Treatment C in Period 3
Sequence BCA	Experimental	Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water, Drug: Ticagrelor OD tablet (90 mg single dose) administered without water, Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of waterTreatment B in Period 1, Treatment C in Period 2 and Treatment A in Period 3
Sequence CAB	Experimental	Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water, Drug: Ticagrelor OD tablet (90 mg single dose) administered without water, Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of waterTreatment C in Period 1, Treatment A in Period 2 and Treatment B in Period 3
Sequence ACB	Experimental	Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water, Drug: Ticagrelor OD tablet (90 mg single dose) administered without water, Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of waterTreatment A in Period 1, Treatment C in Period 2 and Treatment B in Period 3
Sequence BAC	Experimental	Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water, Drug: Ticagrelor OD tablet (90 mg single dose) administered without water, Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of waterTreatment B in Period 1, Treatment A in Period 2 and Treatment C in Period 3
Sequence CBA	Experimental	Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water, Drug: Ticagrelor OD tablet (90 mg single dose) administered without water, Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of waterTreatment C in Period 1, Treatment B in Period 2 and Treatment A in Period 3

Who may qualify

Ages: 20 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (14 listed)

Healthy male and female subjects aged 20 to 45 years with suitable veins for cannulation or repeated venepuncture.
Be Japanese. Japanese is defined as having both parents and four grandparents who are Japanese. This includes second and third generation Japanese whose parents or grandparents are living in a country other than Japan.
Females must have a negative pregnancy test at screening and on each admission to the clinical unit, must not be lactating, and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
Have a body mass index (BMI) between 18.0 and 27.0 kg/m2 inclusive and weigh at least 45 kg and no more than 85 kg inclusive.
Be able and willing to communicate with the investigator and comply with all study procedures, including reproductive restrictions.

Key exclusion criteria (0 listed)

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
Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of waterAlso: Treatment ATicagrelor 90 mg OD tablet, single dose	Drug	Sequence ABC, Sequence ACB, Sequence BAC, Sequence BCA, Sequence CAB, Sequence CBA
Ticagrelor OD tablet (90 mg single dose) administered without waterAlso: Treatment BTicagrelor 90 mg OD tablet, single dose	Drug	Sequence ABC, Sequence ACB, Sequence BAC, Sequence BCA, Sequence CAB, Sequence CBA
Ticagrelor IR tablet (90 mg) administered with 150 mL of waterAlso: Treatment CTicagrelor 90 mg IR tablet, single dose	Drug	Sequence ABC, Sequence ACB, Sequence BAC, Sequence BCA, Sequence CAB, Sequence CBA

Primary outcome

Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Comparison of Cmax (maximum observed plasma concentration) of ticagrelor and its active metabolite AR-C124910XX following single doses of the orodispersible (OD) tablet - when administered with and without water - and ticagrelor immediate-release (IR) tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte Concentration AUC (0-t) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Comparison of AUC(0-t) (Area under the plasma concentration-time curve from time zero to time of last quantifiable analyte concentration) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Comparison of AUC (Area under plasma concentration-time curve from zero to infinity) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).

13 secondary outcomes

Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Terminal Elimination Rate Constant (λz) of Ticagrelor and Its Active Metabolite, AR-C124910XX.
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Mean Residence Time (MRT) of Ticagrelor and Its Active Metabolite AR-C124910XX
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
MRCmax (Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights) of Active Metabolite AR-C124910XX
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Ratio of Metabolite AUC(0-t) to Parent AUC(0-t), Adjusted for Differences in Molecular Weights (MRAUC [0-t]) of Active Metabolite AR-C124910XX
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Ratio of Metabolite AUC to Parent AUC, Adjusted for Differences in Molecular Weights (MRAUC) of Active Metabolite AR-C124910XX
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Number of Participants With Adverse Events (AEs)
Time frame: From the date of randomization (Day 1 of the first treatment period) until the final follow-up visit (5 to 10 days after last administration of IMP).
Elimination Rate Constant (Kel) of Ticagrelor and Its Active Metabolite AR-C124910XX
Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP)
Time frame: Day 1 (pre dose, 2 hours, and 4 hours post dose) and Day 2 (24 hours post dose).
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Time frame: At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart) and during treatment periods at pre-dose and post-dose at 2, 4 and 24 hours.
Participants With Significant Findings in 12-Lead Electrocardiography (ECG).
Time frame: At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart).
Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis.
Time frame: At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart).

Results and safety

Results posted to the registry on 11 Jan 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ABC Sequence	7	7
BCA Sequence	7	6
CAB Sequence	7	7
ACB Sequence	7	7
BAC Sequence	7	7
CBA Sequence	7	7

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.

Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Treatment A n = 41	Treatment B n = 41	Treatment C n = 41
Ticagrelor	529 (38.4)	534 (29.8)	569 (37.0)
AR-C124910XX	165 (31.4)	158 (36.5)	170 (35.5)

Treatment A vs Treatment C: Geometric Mean Ratio: 93.16 (90% CI 85.80 to 101.15), ANOVA
Treatment B vs Treatment C: Geometric mean ratio: 93.67 (90% CI 87.88 to 99.84), ANOVA
Treatment A vs Treatment C: Geometric mean ratio: 96.79 (90% CI 88.27 to 106.14), ANOVA

Population analysed: The pharmacokinetic (PK) analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product \[Treatment C\]) and who had no major protocol deviations.

Primary outcome: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte Concentration AUC (0-t) of Ticagrelor and Its Active Metabolite AR-C124910XX.

Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.. Geometric mean (Geometric Coefficient of Variation). Unit: h*ng/mL

Measure	Treatment A n = 41	Treatment B n = 41	Treatment C n = 41
Ticagrelor	3462 (43.8)	3423 (41.4)	3546 (45.0)
AR-C124910XX	1488 (23.5)	1441 (24.5)	1513 (22.7)

Treatment A vs Treatment C: Geometric Mean Ratio: 97.76 (90% CI 94.46 to 101.18), ANOVA
Treatment B vs Treatment C: Geometric Mean ratio: 96.38 (90% CI 93.24 to 99.63), ANOVA
Treatment A vs Treatment C: Geometric mean ratio: 98.43 (90% CI 94.75 to 102.25), ANOVA

Population analysed: The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product \[Treatment C\]) and who had no major protocol deviations.

Primary outcome: Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC) of Ticagrelor and Its Active Metabolite AR-C124910XX.

Time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	Treatment A n = 41	Treatment B n = 41	Treatment C n = 41
Ticagrelor	3520 (45.1)	3485 (42.8)	3606 (46.3)
AR-C124910XX	1547 (23.3)	1503 (24.0)	1573 (22.3)

Treatment A vs Treatment C: Geometric Mean Ratio: 97.75 (90% CI 94.40 to 101.21), ANOVA
Treatment B vs Treatment C: Geometric mean ratio: 96.50 (90% CI 93.31 to 99.80), ANOVA
Treatment A vs Treatment C: Geometric mean ratio: 98.46 (90% CI 94.85 to 102.20), ANOVA

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment A	0 of 41 (0%)	3 of 41 (7.3%)	Not reported
Treatment B	0 of 41 (0%)	4 of 41 (9.8%)	Not reported
Treatment C	0 of 41 (0%)	3 of 41 (7.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Annelize Koch, Dr. principal investigator

PAREXEL Early Phase Clinical Unit London

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 14 inclusion and 0 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 11 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

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 11 Jan 2017). 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?

Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. (time frame: 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours in each treatment period.). 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 NCT02436577.

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 11 Jan 2017.