An Open-label, Randomised, Four-period, Four-treatment, Crossover, Single-centre, Single-dose Study to Assess the Bioavailability of Ticagrelor Orodispersible Tablets, Compared to Ticagrelor Immediate-release Tablets in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water
- Conditions
- Bioavailability
- Sponsor
- AstraZeneca
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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
Detailed 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.
Investigators
Eligibility 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.
Arms & Interventions
Treatments A-D-B-C sequence
Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water
Treatments A-D-B-C sequence
Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) administered without water
Treatments A-D-B-C sequence
Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube
Treatments A-D-B-C sequence
Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4
Intervention: Brilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water
Treatments B-A-C-D sequence
Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water
Treatments C-B-D-A sequence
Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) administered without water
Treatments B-A-C-D sequence
Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) administered without water
Treatments B-A-C-D sequence
Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube
Treatments B-A-C-D sequence
Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4
Intervention: Brilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water
Treatments C-B-D-A sequence
Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water
Treatments C-B-D-A sequence
Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube
Treatments C-B-D-A sequence
Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4
Intervention: Brilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water
Treatments D-C-A-B sequence
Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water
Treatments D-C-A-B sequence
Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) administered without water
Treatments D-C-A-B sequence
Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4
Intervention: Ticagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube
Treatments D-C-A-B sequence
Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4
Intervention: Brilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water
Outcomes
Primary Outcomes
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.
Blood samples for the determination of plasma concentrations of both ticagrelor and AR-C124910XX were collected at pre-dose (0 hours) and post-dose at 0.5, 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 [0-∞]).
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.
Blood samples for the determination of plasma concentrations of both ticagrelor and AR-C124910XX were collected at pre-dose (0 hours) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
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.
Blood samples for the determination of plasma concentrations of both ticagrelor and AR-C124910XX were collected at pre-dose (0 hours) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).
Secondary Outcomes
- Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX.(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 Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights (MRCmax) of Metabolite AR-C124910XX.(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 in Supine Pulse Rate.(Day 1 (2, 4 hours post-dose) and Day 2 (24 hours post-dose).)
- Ratio of Metabolite AUC(0-t) to Parent AUC(0-t), Adjusted for Differences in Molecular Weights (MRAUC[0-t]) of Metabolite AR-C124910XX.(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.)
- Participants With Significant Findings in 12-Lead Electrocardiography (ECG).(At screening and at follow-up.)
- Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.(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-∞] to Parent AUC [0-∞], Adjusted for Differences in Molecular Weights (MRAUC [0-∞]) of Metabolite AR-C124910XX.(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).(Day 1 (2, 4 hours post-dose) and Day 2 (24 hours post-dose).)
- Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis.(At screening, at admission on Day -1 to each treatment period and at follow-up.)
- Percentage of Participants With Adverse Events (AEs).(SAEs were recorded from the signing of informed consent and AEs were recorded from randomisation until the final follow-up visit.)