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

Healthy Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02400333
• Other study ID #: D5139C00003
• Status: Completed
• Phase: Phase 1
• First received: March 9, 2015
• Last updated: August 4, 2015
• Start date: June 2015
• Est. completion date: July 2015

Study information

• Verified date: August 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bioavailability
• Healthy Subjects

Intervention

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

Locations

Country	Name	City	State
Germany	Research Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rate and extent of absorption of ticagrelor following single dose administration of the OD tablet compared to the IR tablet by assessment of 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 OD tablet when administered with water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets	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	No
Primary	rate and extent of absorption of ticagrelor following single dose administration of the OD tablet compared to the IR tablet by assessment of 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 water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets	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	No
Primary	rate and extent of absorption of ticagrelor following single dose administration of the OD tablet compared to the IR tablet by assessment of 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 water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets	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	No
Secondary	pharmacokinetic profile of ticagrelor following single dose administration of the OD tablet compared to the IR tablet by assessment of 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 water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets	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	No
Secondary	pharmacokinetic profile of ticagrelor following single dose administration of the OD tablet compared to the IR tablet by assessment of t½?z of ticagrelor and its active metabolite AR-C124910XX	comparison of t½?z (half-life associated with terminal slope (?z) 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 water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets	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	No
Secondary	pharmacokinetic profile of ticagrelor following single dose administration of the OD tablet compared to the IR tablet by assessment of MRCmax of ticagrelor and its active metabolite AR-C124910XX	assesssment 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 water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets	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	No
Secondary	pharmacokinetic profile of ticagrelor following single dose administration of the OD tablet compared to the IR tablet by assessment of MRAUC(0-t) of ticagrelor and its active metabolite AR-C124910XX	assesssment 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 water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets	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	No
Secondary	pharmacokinetic profile of ticagrelor following single dose administration of the OD tablet compared to the IR tablet by assessment of MRAUC of ticagrelor and its active metabolite AR-C124910XX	assesssment 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 water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets	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	No
Secondary	Safety of ticagrelor by assessing adverse events	To assess safety and tolerability of ticagrelor OD tablets when administered with water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets; (Participants will stay at the clinic at 4 different periods, each period spanning over 3 days and with 7 days wash-out between the periods. Thus the overall period, incl. wash-out, is approximately 3+3+3+3+7+7+7=33 days).	from baseline to Day 33	Yes
Secondary	Safety of ticagrelor by assessing vital signs (blood pressure and pulse)	To assess safety and tolerability of ticagrelor OD tablets when administered with water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets (Participants will stay at the clinic at 4 different periods, each period spanning over 3 days and with 7 days wash-out between the periods. Thus the overall period, incl. wash-out, is approximately 3+3+3+3+7+7+7=33 days).	from baseline to Day 33	Yes
Secondary	Safety of ticagrelor by assessing Electrocardiogram (ECG)	To assess safety and tolerability of ticagrelor OD tablets when administered with water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets. (The Participants will be involved in the study for 7 to 8 weeks and ECGs are performed at the beginning (Screening) and end (Follow-up)).	at screening and at follow-up (these two examinations are 7 to 8 weeks apart)	Yes
Secondary	Safety of ticagrelor by laboratory assessments (haematology, clinical chemistry and urinalysis).	To assess safety and tolerability of ticagrelor OD tablets when administered with water, without water and suspended in water to be administered through nasogastric tubes, compared to ticagrelor IR tablets (The Participants will be involved in the study for 7 to 8 weeks and safety laboratory assessments are performed at the beginning (Screening), at admission on Day -1 to each treatment period and end (Follow-up).	at screening, at admission on Day -1 to each treatment period and at follow-up (the first and last examination are 7 to 8 weeks apart)	Yes