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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Bioequivalence; Healthy Japanese Subjects; Pharmacokinetics

Treatments: Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water; 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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02436577

D5139C00004

Details and patient eligibility

About

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.

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.

Full description

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

Enrollment: 51 patients

Sex: All

Ages: 20 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• 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.

• 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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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51 participants in 6 patient groups

Sequence ABC

Experimental group

Description:

Treatment A in Period 1, Treatment B in Period 2 and Treatment C in Period 3

Treatment:

Drug: Ticagrelor OD tablet (90 mg single dose) administered without water

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water

Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water

Sequence BCA

Experimental group

Description:

Treatment B in Period 1, Treatment C in Period 2 and Treatment A in Period 3

Treatment:

Drug: Ticagrelor OD tablet (90 mg single dose) administered without water

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water

Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water

Sequence CAB

Experimental group

Description:

Treatment C in Period 1, Treatment A in Period 2 and Treatment B in Period 3

Treatment:

Drug: Ticagrelor OD tablet (90 mg single dose) administered without water

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water

Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water

Sequence ACB

Experimental group

Description:

Treatment A in Period 1, Treatment C in Period 2 and Treatment B in Period 3

Treatment:

Drug: Ticagrelor OD tablet (90 mg single dose) administered without water

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water

Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water

Sequence BAC

Experimental group

Description:

Treatment B in Period 1, Treatment A in Period 2 and Treatment C in Period 3

Treatment:

Drug: Ticagrelor OD tablet (90 mg single dose) administered without water

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water

Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water

Sequence CBA

Experimental group

Description:

Treatment C in Period 1, Treatment B in Period 2 and Treatment A in Period 3

Treatment:

Drug: Ticagrelor OD tablet (90 mg single dose) administered without water

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water

Drug: Ticagrelor IR tablet (90 mg) administered with 150 mL of water