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

Pharmacokinetics Clinical Trial

Official title:

An Open-label, Randomized, Three-period, Three-treatment, Crossover, Single-centre, Single-dose Study to Assess the Bioequivalence Between Ticagrelor Orodispersible Tablets and Ticagrelor Immediate-release Tablets in Healthy Japanese Subjects.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02436577
• Other study ID #: D5139C00004
• Status: Completed
• Phase: Phase 1
• First received: April 7, 2015
• Last updated: September 7, 2015
• Start date: June 2015
• Est. completion date: August 2015

Study information

• Verified date: September 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 45 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Bioequivalence
• Healthy Japanese Subjects
• Pharmacokinetics

Intervention

Drug:
• Ticagrelor OD tablet (90 mg single dose) administered with 150 mL of water
Ticagrelor 90 mg OD tablet, single dose
• Ticagrelor OD tablet (90 mg single dose) administered without water
Ticagrelor 90 mg OD tablet, single dose
• Ticagrelor IR tablet (90 mg) administered with 200 mL of water
Ticagrelor 90 mg IR tablet, single dose

Locations

Country	Name	City	State
United Kingdom	Research Site	Harrow

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United Kingdom, 

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 orodispersible (OD) tablet - when administered with and without water - and ticagrelor immediate-release (IR) tablet	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 and without water - and ticagrelor IR tablet	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 and without water - and ticagrelor IR tablet	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 and without water - and ticagrelor IR tablet	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 and without water - and ticagrelor IR tablet	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 mean residence time (MRT) of ticagrelor and its active metabolite AR-C124910XX	Comparison of MRT (mean residence time) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet	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	Assessment 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 and without water - and ticagrelor IR tablet	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	Assessment 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 and without water - and ticagrelor IR tablet	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	Assessment 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 and without water - and ticagrelor IR tablet	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 kel of ticagrelor and its active metabolite AR-C124910XX	Comparison of kel (elimination rate constant) of ticagrelor and its active metabolite AR-C124910XX following single doses of the OD tablet - when administered with and without water - and ticagrelor IR tablet	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 and without water - and ticagrelor IR tablets	At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart) and as applicable, in each period between Day -1 and Day 3	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 and without water - and ticagrelor IR tablets	At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart) and during treatment periods at pre-dose and post-dose at 2, 4 and 24 hours	Yes
Secondary	Safety of ticagrelor by assessing Electrocardiogram (ECG)	To assess safety and tolerability of ticagrelor OD tablets - when administered with and without water - and ticagrelor IR tablets	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 and without water - and ticagrelor IR tablets	At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart)	Yes