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

NCT02400333 | Completed Phase 1 Results

• 1 other identifier: D5139C00003
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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

Conditions

Bioavailability; Healthy Subjects

Keywords

ticagrelor orodispersible tablet; ticagrelor immediate-release tablet; relative bioavailability; Phase I; healthy subjects

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.

  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).

  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.

  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).

  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 [0-∞]).

  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).

  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 (10)

• 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.

• 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.

• 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.

• 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.

Study Arms (4)

Treatments A-D-B-C sequence

EXPERIMENTAL

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

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without 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

Treatments B-A-C-D sequence

EXPERIMENTAL

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

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without 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

Treatments C-B-D-A sequence

EXPERIMENTAL

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

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without 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

Treatments D-C-A-B sequence

EXPERIMENTAL

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

Drug: Ticagrelor OD tablet (90 mg single dose) administered with 200 ml of water; Drug: Ticagrelor OD tablet (90 mg single dose) administered without 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

Interventions

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

90 mg single dose

Also known as: Treatment A

Treatments A-D-B-C sequence; Treatments B-A-C-D sequence; Treatments C-B-D-A sequence; Treatments D-C-A-B sequence

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

90 mg single dose

Also known as: Treatment B

Treatments A-D-B-C sequence; Treatments B-A-C-D sequence; Treatments C-B-D-A sequence; Treatments D-C-A-B sequence

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

90 mg single dose

Also known as: Treatment C

Treatments A-D-B-C sequence; Treatments B-A-C-D sequence; Treatments C-B-D-A sequence; Treatments D-C-A-B sequence

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

90 mg single dose

Also known as: Treatment D

Treatments A-D-B-C sequence; Treatments B-A-C-D sequence; Treatments C-B-D-A sequence; Treatments D-C-A-B sequence

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Berlin, Germany

Location

MeSH Terms

Interventions

Water; Excipients; Ticagrelor

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Pharmaceutical Vehicles; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses; 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

+46 31 7761000

Study Officials

• Rainard Fuhr, Dr. med.

  PAREXEL International GmbH, Berlin

  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: March 9, 2015
• First Posted: March 27, 2015
• Study Start: June 1, 2015
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: September 29, 2016
• Results First Posted: August 3, 2016

Record last verified: 2016-08

Locations

DE (1)