Sickle Cell DiseasePhase 1NCT03126695

A Study to Compare if the Uptake of Ticagrelor in the Body Differs When Different Tablets Are Administered

A Phase 1 study testing Ticagrelor granule, Ticagrelor pediatric tablets and Ticagrelor pediatric tablets suspended in water in people with Sickle Cell Disease, run by AstraZeneca at 1 site in Germany.

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

To evaluate the relative bioavailability of ticagrelor for the different formulations. A randomized cross-over design has been chosen to minimize the effects of between-subject variability and any period effects on the overall results. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Sickle Cell Disease
What is being tested?: Ticagrelor granule, Ticagrelor pediatric tablets and Ticagrelor pediatric tablets suspended in water
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 44 participants
Where: 1 siteGermany
Study dates: 12 May 2017to 24 Jul 2017
Phase: Phase 1
Are there results?: None posted in the registry

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 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Provision of signed and dated written informed consent prior to any study specific procedures.
Healthy male and female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
Females must have a negative pregnancy test at Screening and on each admission to the Clinical Unit, must not be lactating and if of non child-bearing 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 follicle-stimulating hormone (FSH) levels in the post-menopausal range (> 40 milli international units per milliliter (mIU/mL)). - Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. - Childbearing potential and are sexually active must use 1 highly effective method of birth control in combination with a barrier method, from the time of IMP administration until 3 months after the last dose of IMP.
Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
Able to understand, read and speak the German language.

Who cannot join

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 influence the results or the potential subject's ability to participate in the study.
History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
Any clinically significant abnormalities in hematology, clinical chemistry, coagulation or urinalysis results at Screening or Day -1 of Treatment Period 1, as judged by the Investigator.
Any clinically significant abnormal findings in vital signs at Screening or Day -1 of Treatment Period 1, as judged by the Investigator.
Any clinically significant abnormalities on 12-lead ECG at Screening, as judged by the Investigator.

Show all 21Show fewer

Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBcAb), hepatitis C antibodies (anti- HCV) and human immunodeficiency virus (HIV) antibodies.
Has received a new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest.
Plasma donation within 1 month of Screening or any blood donation/loss more than 500 mL during the 3 months prior to Screening. 10. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to ticagrelor.
11. Current smokers or those who have smoked or used nicotine products within the previous 3 months.
12. Positive screen for drugs of abuse or cotinine (cotinine level above 500 ng/mL) at Screening or on each admission to the Clinical Unit or positive screen for alcohol on each admission to the Clinical Unit.
13. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
14. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
15. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol, as judged by the Investigator.
16. Involvement of any AstraZeneca or Clinical Unit employee or their close relatives.
17. Judgment by the Investigator that the potential subject should not participate in the study if they have any ongoing or recent (i.e., during the Screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
18. Consumption of poppy seeds within 7 days of first admission to the Clinical Unit.
19. History of hemophilia, von Willebrand's disease, lupus anticoagulant, or other diseases/syndromes that can either alter or increase the propensity for bleeding. 20. 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.
21. History of a clinically significant non-traumatic bleed or clinically significant bleeding risk, as judged by the Investigator.
22. Use of aspirin, ibuprofen, NSAIDs, or any other drug known to increase the propensity for bleeding for 2 weeks before randomization. 23. Platelet count less than 150 x 109/L.
24. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship or committed to an institution by governmental or juridical order.

Trial locations and contacts

1 site in 1 country.

Germany1 site

Research Site
Berlin, 14050

Other trials in Germany

About this study

Official title: An Open-label, Randomized, 4-period, 4-treatment, Cross-over, Single-center, Single-dose Study to Assess the Relative Bioavailability of Ticagrelor in Different Formulations in Healthy Adult Subjects

Read the detailed description

This study will be an open-label, randomized, 4-period, 4-treatment, cross-over, single-center, single-dose study to assess the relative bioavailability of different formulations of ticagrelor in approximately 44 healthy adult subjects. Eligible subjects will be healthy male and female aged 18 to 55 years, with a body weight of 55 to 100 kg and a body mass index (BMI) of 18 to 30 kg/m2. Of the 44 randomized subjects, at least 36 evaluable subjects should be at the end of the last treatment period. Subjects will be randomized to 1 of 4 treatment sequences and will receive single oral doses of 4 different formulations of ticagrelor under fasted conditions. Subjects will fast for at least 10 hours prior to administration of Investigational Medicinal Products (IMPs). No fluids will be allowed apart from water which can be given until 1 hour prior to administration of the IMP and then from 2 hours after administration of the IMP. A meal can be given 4 hours after administration of the IMP.

Conditions: Sickle Cell Disease
Being tested: Ticagrelor granule, Ticagrelor pediatric tablets, Ticagrelor pediatric tablets suspended in water, Ticagrelor immediate release (IR) tablets (Commercial tablet)
Keywords: Abnormal hemoglobin (called hemoglobin S or sickle hemoglobin) in the red blood cells, Thrombotic cardiovascular events, Acute coronary syndrome, P2Y12 platelet inhibitor, Brilinta
Medical subject headings: Anemia, Sickle Cell, Sickle Cell Trait, Acute Coronary Syndrome

What participants receive

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

Ticagrelor granuleDrug
A P2Y12 receptor inhibitor provided as granule for suspension.
Ticagrelor pediatric tabletsDrug
A P2Y12 receptor inhibitor provided as pediatric tablets to be swallowed whole.
Ticagrelor pediatric tablets suspended in waterDrug
A P2Y12 receptor inhibitor provided as pediatric tablets suspended in water.
Ticagrelor immediate release (IR) tablets (Commercial tablet)Drug
Also called Brilinta
A P2Y12 platelet inhibitor indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (unstable angina, non-ST (S and T waves) elevation MI or ST elevation MI) and in patients with a history of MI

Study groups in NCT03126695
Study group	Role	What they receive
Treatment Sequence 1 (ADBC)	Experimental	Subjects were randomized to treatment sequence ADBC: On Day 1, following an overnight fast of at least 10 hours, each subject will receive single dose of the treatment assigned to that treatment period. A =Ticagrelor granule for oral suspension equal to 90 mg. B = Ticagrelor pediatric tablets equal to 90 mg. C= Ticagrelor pediatric tablets suspended in water equal to 90 mg. D = Ticagrelor commercial IR (1 x 90 mg) tablet Receives: Drug: Ticagrelor granule; Drug: Ticagrelor pediatric tablets; Drug: Ticagrelor pediatric tablets suspended in water; Drug: Ticagrelor immediate release (IR) tablets (Commercial tablet)
Treatment Sequence 2 (BACD)	Experimental	Subjects were randomized to treatment sequence BACD: On Day 1, following an overnight fast of at least 10 hours, each subjects will receive single dose of the treatment assigned to that treatment period. A =Ticagrelor granule for oral suspension equal to 90 mg. B = Ticagrelor pediatric tablets equal to 90 mg. C= Ticagrelor pediatric tablets suspended in water equal to 90 mg. D = Ticagrelor commercial IR (1 x 90 mg) tablet Receives: Drug: Ticagrelor granule; Drug: Ticagrelor pediatric tablets; Drug: Ticagrelor pediatric tablets suspended in water; Drug: Ticagrelor immediate release (IR) tablets (Commercial tablet)
Treatment Sequence 3 (CBDA)	Experimental	Subjects were randomized to treatment sequence CBDA: On Day 1, following an overnight fast of at least 10 hours, each subjects will receive single dose of the treatment assigned to that treatment period. A =Ticagrelor granule for oral suspension equal to 90 mg. B = Ticagrelor pediatric tablets equal to 90 mg. C= Ticagrelor pediatric tablets suspended in water equal to 90 mg. D = Ticagrelor commercial IR (1 x 90 mg) tablet Receives: Drug: Ticagrelor granule; Drug: Ticagrelor pediatric tablets; Drug: Ticagrelor pediatric tablets suspended in water; Drug: Ticagrelor immediate release (IR) tablets (Commercial tablet)
Treatment Sequence 4 (DCAB)	Active comparator	Subjects were randomized to treatment sequence DCAB: On Day 1, following an overnight fast of at least 10 hours, each subjects will receive single dose of the treatment assigned to that treatment period. A =Ticagrelor granule for oral suspension equal to 90 mg. B = Ticagrelor pediatric tablets equal to 90 mg. C= Ticagrelor pediatric tablets suspended in water equal to 90 mg. D = Ticagrelor commercial IR (1 x 90 mg) tablet Receives: Drug: Ticagrelor granule; Drug: Ticagrelor pediatric tablets; Drug: Ticagrelor pediatric tablets suspended in water; Drug: Ticagrelor immediate release (IR) tablets (Commercial tablet)

What is being measured

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

Maximum observed plasma concentration (Cmax)
- To determine the relative bioavailability of ticagrelor granule for oral suspension and the pediatric ticagrelor tablet to the commercial ticagrelor tablet in healthy subjects.
- To determine the relative bioavailability of ticagrelor pediatric tablet taken whole and the pediatric tablet dispersed in water to the granule for oral suspension in healthy subjects.
- To evaluate the bioequivalence between the pediatric ticagrelor tablet taken whole and the pediatric ticagrelor tablet dispersed in water in healthy subjects.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Area under plasma concentration-time curve from zero to infinity (AUC)
- To determine the relative bioavailability of ticagrelor granule for oral suspension and the pediatric ticagrelor tablet to the commercial ticagrelor tablet in healthy subjects.
- To determine the relative bioavailability of ticagrelor pediatric tablet taken whole and the pediatric tablet dispersed in water to the granule for oral suspension in healthy subjects.
- To evaluate the bioequivalence between the pediatric ticagrelor tablet taken whole and the pediatric ticagrelor tablet dispersed in water in healthy subjects.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose.

Secondary outcomes (16)

Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC(0-t))
To compare the pharmacokinetic (PK) profiles of ticagrelor and its active metabolite (AR-C124910XX) in healthy subjects when administered as granule for oral suspension, pediatric ticagrelor tablet, pediatric ticagrelor tablet suspended in water and commercial ticagrelor tablet.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Time to reach maximum observed plasma concentration, taken directly from the individual concentration-time curve (tmax).
To compare the PK profiles of ticagrelor and its active metabolite (AR-C124910XX) in healthy subjects when administered as granule for oral suspension, pediatric ticagrelor tablet, pediatric ticagrelor tablet suspended in water and commercial ticagrelor tablet.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz).
To compare the PK profiles of ticagrelor and its active metabolite (AR-C124910XX) in healthy subjects when administered as granule for oral suspension, pediatric ticagrelor tablet, pediatric ticagrelor tablet suspended in water and commercial ticagrelor tablet.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Terminal rate constant, estimated by log-linear regression of the terminal part of the concentration-time curve (λz).
To compare the PK profiles of ticagrelor and its active metabolite (AR-C124910XX) in healthy subjects when administered as granule for oral suspension, pediatric ticagrelor tablet, pediatric ticagrelor tablet suspended in water and commercial ticagrelor tablet.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Apparent clearance, estimated as dose divided by AUC (ticagrelor only) (CL/F).
To compare the PK profiles of ticagrelor and its active metabolite (AR-C124910XX) in healthy subjects when administered as granule for oral suspension, pediatric ticagrelor tablet, pediatric ticagrelor tablet suspended in water and commercial ticagrelor tablet.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Apparent volume of distribution at the terminal phase, estimated by dividing the apparent clearance (CL/F) by λz (ticagrelor only) (Vz/F).
To compare the PK profiles of ticagrelor and its active metabolite (AR-C124910XX) in healthy subjects when administered as granule for oral suspension, pediatric ticagrelor tablet, pediatric ticagrelor tablet suspended in water and commercial ticagrelor tablet.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Ratio of metabolite Cmax to parent Cmax, adjusted for differences in molecular weights (MRCmax).
To compare the PK profiles of ticagrelor and its active metabolite (AR-C124910XX) in healthy subjects when administered as granule for oral suspension, pediatric ticagrelor tablet, pediatric ticagrelor tablet suspended in water and commercial ticagrelor tablet.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Ratio of metabolite AUC(0-t) to parent AUC(0-t), adjusted for differences in molecular weights (MRAUC(0-t)).
To compare the PK profiles of ticagrelor and its active metabolite (AR-C124910XX) in healthy subjects when administered as granule for oral suspension, pediatric ticagrelor tablet, pediatric ticagrelor tablet suspended in water and commercial ticagrelor tablet.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Ratio of metabolite AUC to parent AUC, adjusted for differences in molecular weights (MRAUC)
To compare the PK profiles of ticagrelor and its active metabolite (AR-C124910XX) in healthy subjects when administered as granule for oral suspension, pediatric ticagrelor tablet, pediatric ticagrelor tablet suspended in water and commercial ticagrelor tablet.
Measured: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Number of patients with Adverse Events (AEs)
To assess the adverse events as a criteria of safety and tolerability variables.
Measured: From screening (day -28) until follow-up/early termination (ET) (Day 5 to Day 10 (after treatment Period 4/ET))
Vital sign (systolic and diastolic blood pressure [BP])
To assess the vital signs as a criteria of safety and tolerability variables.
Measured: At screening (Day -28), admission (Day -1), treatment periods 1, 2, 3, 4 (Day 1 - 3) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Vital sign (pulse rate)
To assess the vital signs as a criteria of safety and tolerability variables.
Measured: At screening (Day -28), admission (Day -1), treatment periods 1, 2, 3, 4 (Day 1 - 3) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Twelve-lead electrocardiograms (ECGs)
To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.
Measured: At screening (Day -28) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Physical examination
To assess the physical examination as a criteria of safety and tolerability variables.
Measured: At screening (Day -28) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Laboratory assessments (hematology and clinical chemistry)
To assess the hematology and clinical chemistry as a criteria of safety and tolerability variables.
Measured: At screening (Day -28), admission (day -1) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Laboratory assessments (Urinalysis (dipstick))
To assess the urinalysis as a criteria of safety and tolerability variables.
Measured: At screening (Day -28), admission (day -1) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))

Timeline

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

12 May 201724 Jul 2017

First posted24 Apr 2017
Study start12 May 2017
Primary completion24 Jul 2017
Study completion24 Jul 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Sickle Cell DiseaseStudies 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: Other
Allocation: Randomised
Intervention model: Crossover
Model description: A randomized cross-over design has been chosen to minimize the effects of between-subject variability and any period effects on the overall results.
Masking: None (open label)
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03126695
Sponsor's protocol ID: D5136C00011
Status last verified: Jul 2017
First submitted: 20 Apr 2017
Last updated: 2 Aug 2017
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Niazi M, Wissmar J, Berggren AR, Karlsson C, Johanson P. Development Strategy and Relative Bioavailability of a Pediatric Tablet Formulation of Ticagrelor. Clin Drug Investig. 2019 Aug;39(8):765-773. doi: 10.1007/s40261-019-00800-w.
PubMed 31140114

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?

See locations

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All Sickle Cell Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Randomized, 4-period, 4-treatment, Cross-over, Single-center, Single-dose Study to Assess the Relative Bioavailability of Ticagrelor in Different Formulations in Healthy Adult Subjects
ClinicalTrials.gov ID: NCT03126695
Acronym / sponsor ID: D5136C00011
Conditions: Sickle Cell Disease
Keywords: Abnormal hemoglobin (called hemoglobin S or sickle hemoglobin) in the red blood cells, Thrombotic cardiovascular events, Acute coronary syndrome, P2Y12 platelet inhibitor, Brilinta
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Parexel
Study start: 12 May 2017 (actual)
Primary completion: 24 Jul 2017 (actual)
Study completion: 24 Jul 2017 (actual)
First posted: 24 Apr 2017 (actual)
Results: Not posted in the source record

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

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 4
Model description: A randomized cross-over design has been chosen to minimize the effects of between-subject variability and any period effects on the overall results.

Arm	Type	Receives
Treatment Sequence 1 (ADBC)	Experimental	Drug: Ticagrelor granule, Drug: Ticagrelor pediatric tablets, Drug: Ticagrelor pediatric tablets suspended in water, Drug: Ticagrelor immediate release (IR) tablets (Commercial tablet)Subjects were randomized to treatment sequence ADBC: On Day 1, following an overnight fast of at least 10 hours, each subject will receive single dose of the treatment assigned to that treatment period. A =Ticagrelor granule for oral suspension equal to 90 mg. B = Ticagrelor pediatric tablets equal to 90 mg. C= Ticagrelor pediatric tablets suspended in water equal to 90 mg. D = Ticagrelor commercial IR (1 x 90 mg) tablet
Treatment Sequence 2 (BACD)	Experimental	Drug: Ticagrelor granule, Drug: Ticagrelor pediatric tablets, Drug: Ticagrelor pediatric tablets suspended in water, Drug: Ticagrelor immediate release (IR) tablets (Commercial tablet)Subjects were randomized to treatment sequence BACD: On Day 1, following an overnight fast of at least 10 hours, each subjects will receive single dose of the treatment assigned to that treatment period. A =Ticagrelor granule for oral suspension equal to 90 mg. B = Ticagrelor pediatric tablets equal to 90 mg. C= Ticagrelor pediatric tablets suspended in water equal to 90 mg. D = Ticagrelor commercial IR (1 x 90 mg) tablet
Treatment Sequence 3 (CBDA)	Experimental	Drug: Ticagrelor granule, Drug: Ticagrelor pediatric tablets, Drug: Ticagrelor pediatric tablets suspended in water, Drug: Ticagrelor immediate release (IR) tablets (Commercial tablet)Subjects were randomized to treatment sequence CBDA: On Day 1, following an overnight fast of at least 10 hours, each subjects will receive single dose of the treatment assigned to that treatment period. A =Ticagrelor granule for oral suspension equal to 90 mg. B = Ticagrelor pediatric tablets equal to 90 mg. C= Ticagrelor pediatric tablets suspended in water equal to 90 mg. D = Ticagrelor commercial IR (1 x 90 mg) tablet
Treatment Sequence 4 (DCAB)	Active comparator	Drug: Ticagrelor granule, Drug: Ticagrelor pediatric tablets, Drug: Ticagrelor pediatric tablets suspended in water, Drug: Ticagrelor immediate release (IR) tablets (Commercial tablet)Subjects were randomized to treatment sequence DCAB: On Day 1, following an overnight fast of at least 10 hours, each subjects will receive single dose of the treatment assigned to that treatment period. A =Ticagrelor granule for oral suspension equal to 90 mg. B = Ticagrelor pediatric tablets equal to 90 mg. C= Ticagrelor pediatric tablets suspended in water equal to 90 mg. D = Ticagrelor commercial IR (1 x 90 mg) tablet

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Provision of signed and dated written informed consent prior to any study specific procedures.
Healthy male and female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
Females must have a negative pregnancy test at Screening and on each admission to the Clinical Unit, must not be lactating and if of non child-bearing potential, confirmed at Screening by fulfilling one of the following criteria:
Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
Able to understand, read and speak the German language.

Key exclusion criteria (21 listed)

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 influence the results or the potential subject's ability to participate in the study.
History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
Any clinically significant abnormalities in hematology, clinical chemistry, coagulation or urinalysis results at Screening or Day -1 of Treatment Period 1, as judged by the Investigator.
Any clinically significant abnormal findings in vital signs at Screening or Day -1 of Treatment Period 1, as judged by the Investigator.

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 granuleA P2Y12 receptor inhibitor provided as granule for suspension.	Drug	Treatment Sequence 1 (ADBC), Treatment Sequence 2 (BACD), Treatment Sequence 3 (CBDA), Treatment Sequence 4 (DCAB)
Ticagrelor pediatric tabletsA P2Y12 receptor inhibitor provided as pediatric tablets to be swallowed whole.	Drug	Treatment Sequence 1 (ADBC), Treatment Sequence 2 (BACD), Treatment Sequence 3 (CBDA), Treatment Sequence 4 (DCAB)
Ticagrelor pediatric tablets suspended in waterA P2Y12 receptor inhibitor provided as pediatric tablets suspended in water.	Drug	Treatment Sequence 1 (ADBC), Treatment Sequence 2 (BACD), Treatment Sequence 3 (CBDA), Treatment Sequence 4 (DCAB)
Ticagrelor immediate release (IR) tablets (Commercial tablet)Also: BrilintaA P2Y12 platelet inhibitor indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (unstable angina, non-ST (S and T waves) elevation MI or ST elevation MI) and in patients with a history of MI	Drug	Treatment Sequence 1 (ADBC), Treatment Sequence 2 (BACD), Treatment Sequence 3 (CBDA), Treatment Sequence 4 (DCAB)

Primary outcome

Maximum observed plasma concentration (Cmax)
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
* To determine the relative bioavailability of ticagrelor granule for oral suspension and the pediatric ticagrelor tablet to the commercial ticagrelor tablet in healthy subjects. * To determine the relative bioavailability of ticagrelor pediatric tablet taken whole and the pediatric tablet dispersed in water to the granule for oral suspension in healthy subjects. * To evaluate the bioequivalence between the pediatric ticagrelor tablet taken whole and the pediatric ticagrelor tablet dispersed in water in healthy subjects.
Area under plasma concentration-time curve from zero to infinity (AUC)
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose.
* To determine the relative bioavailability of ticagrelor granule for oral suspension and the pediatric ticagrelor tablet to the commercial ticagrelor tablet in healthy subjects. * To determine the relative bioavailability of ticagrelor pediatric tablet taken whole and the pediatric tablet dispersed in water to the granule for oral suspension in healthy subjects. * To evaluate the bioequivalence between the pediatric ticagrelor tablet taken whole and the pediatric ticagrelor tablet dispersed in water in healthy subjects.

16 secondary outcomes

Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC(0-t))
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Time to reach maximum observed plasma concentration, taken directly from the individual concentration-time curve (tmax).
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz).
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Terminal rate constant, estimated by log-linear regression of the terminal part of the concentration-time curve (λz).
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Apparent clearance, estimated as dose divided by AUC (ticagrelor only) (CL/F).
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Apparent volume of distribution at the terminal phase, estimated by dividing the apparent clearance (CL/F) by λz (ticagrelor only) (Vz/F).
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Ratio of metabolite Cmax to parent Cmax, adjusted for differences in molecular weights (MRCmax).
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Ratio of metabolite AUC(0-t) to parent AUC(0-t), adjusted for differences in molecular weights (MRAUC(0-t)).
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Ratio of metabolite AUC to parent AUC, adjusted for differences in molecular weights (MRAUC)
Time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period
Number of patients with Adverse Events (AEs)
Time frame: From screening (day -28) until follow-up/early termination (ET) (Day 5 to Day 10 (after treatment Period 4/ET))
Vital sign (systolic and diastolic blood pressure [BP])
Time frame: At screening (Day -28), admission (Day -1), treatment periods 1, 2, 3, 4 (Day 1 - 3) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Vital sign (pulse rate)
Time frame: At screening (Day -28), admission (Day -1), treatment periods 1, 2, 3, 4 (Day 1 - 3) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Twelve-lead electrocardiograms (ECGs)
Time frame: At screening (Day -28) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Physical examination
Time frame: At screening (Day -28) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Laboratory assessments (hematology and clinical chemistry)
Time frame: At screening (Day -28), admission (day -1) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))
Laboratory assessments (Urinalysis (dipstick))
Time frame: At screening (Day -28), admission (day -1) and follow-up/ET (Day 5 to Day 10 (after treatment Period 4/ET))

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2017.
Derived from this study: PubMed 31140114Niazi M, Wissmar J, Berggren AR, Karlsson C, Johanson P. Development Strategy and Relative Bioavailability of a Pediatric Tablet Formulation of Ticagrelor. Clin Drug Investig. 2019 Aug;39(8):765-773. doi: 10.1007/s40261-019-00800-w.

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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.

Rainard Fuhr, Dr. med. principal investigator

PAREXEL Early Phase Clinical Unit Berlin

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 6 inclusion and 21 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 2 Aug 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 Germany. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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) (time frame: At 0 hours (pre-dose) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose in each treatment period). The study lists 2 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 NCT03126695, 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 2 Aug 2017.