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

NCT02436577 | Completed Phase 1 Results

• 1 other identifier: D5139C00004
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bioequivalence; Healthy Japanese Subjects; Pharmacokinetics

Keywords

ticagrelor orodispersible tablet; ticagrelor immediate-release tablet; bioequivalence; Phase I; healthy Japanese subjects

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (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. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).

  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.

• 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.

  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. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).

  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.

• Area Under Plasma Concentration-time Curve From Zero to Infinity (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. Blood samples for the determination of plasma concentrations of both ticagrelor and its active metabolite AR-C124910XX will be collected for each treatment period: 0 hours (pre-dose) and post-dose at 0.5 (30 minutes), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours (14 samples per treatment period).

  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.

Secondary Outcomes (13)

• 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.

• 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.

• Terminal Elimination Rate Constant (λz) 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.

• Mean Residence Time (MRT) 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.

• MRCmax (Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights) of 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.

Study Arms (6)

Sequence ABC

EXPERIMENTAL

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

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

Sequence BCA

EXPERIMENTAL

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

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

Sequence CAB

EXPERIMENTAL

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

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

Sequence ACB

EXPERIMENTAL

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

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

Sequence BAC

EXPERIMENTAL

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

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

Sequence CBA

EXPERIMENTAL

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

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

Interventions

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

Ticagrelor 90 mg OD tablet, single dose

Also known as: Treatment A

Sequence ABC; Sequence ACB; Sequence BAC; Sequence BCA; Sequence CAB; Sequence CBA

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

Ticagrelor 90 mg OD tablet, single dose

Also known as: Treatment B

Sequence ABC; Sequence ACB; Sequence BAC; Sequence BCA; Sequence CAB; Sequence CBA

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

Ticagrelor 90 mg IR tablet, single dose

Also known as: Treatment C

Sequence ABC; Sequence ACB; Sequence BAC; Sequence BCA; Sequence CAB; Sequence CBA

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Harrow, United Kingdom

Location

MeSH Terms

Interventions

Water; Ticagrelor

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Brilinta Global Clinical Leader
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

+46317761000

Study Officials

• Annelize Koch, Dr.

  PAREXEL Early Phase Clinical Unit London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2015
• First Posted: May 7, 2015
• Study Start: June 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: January 11, 2017
• Results First Posted: January 11, 2017

Record last verified: 2016-11

Locations

GB (1)