Study to Assess the Bioavailability of Ticagrelor OD Tablet vs. IR Tablet

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects; Bioavailability

Treatments: Drug: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water; Drug: Ticagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube; Drug: Brilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without water

Study type: Interventional

Funder types: Industry

Identifiers

NCT02400333

D5139C00003

Details and patient eligibility

About

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

The objective of the study is to assess the bioavailability of ticagrelor orodispersible (OD) tablets when administered with water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor immediate-release (IR) tablets

Full description

Study to evaluate the bioavailability of ticagrelor OD tablets administered with water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets.

Enrollment: 100 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Healthy male and female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venepuncture. - 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 amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range or Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. - Have a body mass index (BMI) between 18.5 and 29.9 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.

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 influence the results or the potential subject's ability to participate in the study.

• Any abnormalities in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), urea, creatinine, thyroid-stimulating hormone (TSH), International Normalised Ratio (INR), activated partial thromboplastin time (aPTT), white blood cell (WBC) count, haemoglobin (Hb) or platelet count. Any other abnormal haematology, clinical chemistry, coagulation or urinalysis results, as judged with an unacceptable deviation that is considered to be clinically significant by the investigator.

• Any clinically significant abnormal findings in vital signs, as judged by the investigator. at screening and at baseline (Day -1 of Treatment period 1), defined as:

  • Systolic blood pressure < 90mmHg or ≥ 140 mmHg
  • Diastolic blood pressure < 50mmHg or ≥ 90 mmHg
  • Pulse < 50 or > 85 beats per minute (bpm)

• Current smokers or those who have smoked or used nicotine products within the previous 3 months.

• History of haemophilia, 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 haemorrhage, hematemesis, melena, haemoptysis, severe epistaxis, severe thrombocytopenia, intracranial haemorrhage; 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 randomisation.

• Platelet count less than 150 x 109/L.

Criteria applicable to insertion of a nasogastric tube:

• History of severe midface trauma and/or recent nasal surgery.
• History of coagulation abnormality, oesophageal varices or stricture, recent banding or cautery of oesophageal varices, and/or alkaline ingestion, at the discretion of the investigator.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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100 participants in 4 patient groups

Treatments A-D-B-C sequence

Experimental group

Description:

Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4

Treatment:

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

Drug: Brilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water

Drug: Ticagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water

Treatments B-A-C-D sequence

Experimental group

Description:

Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4

Treatment:

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

Drug: Brilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water

Drug: Ticagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water

Treatments C-B-D-A sequence

Experimental group

Description:

Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4

Treatment:

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

Drug: Brilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water

Drug: Ticagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water

Treatments D-C-A-B sequence

Experimental group

Description:

Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4

Treatment:

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

Drug: Brilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water

Drug: Ticagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water