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Phase 1 Completed N=36 Randomized Basic Science

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

Bioavailability · Healthy Subjects
Source: ClinicalTrials.gov NCT02400333 ↗
Enrolled (actual)
36
Serious AEs
0.0%
Results posted
Aug 2016
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. — 428; 499; 479; 520 ng/mL

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

Outcome Measures

OutcomeResultp-value
PRIMARY
Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
428; 499; 479; 520; 118; 126
PRIMARY
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.
3023; 3172; 3174; 3358; 1087; 1104
PRIMARY
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]).
3068; 3228; 3226; 3423; 1138; 1155
SECONDARY
Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
2.02; 2.00; 2.00; 2.00; 3.00; 3.00
SECONDARY
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX.
8.02; 8.21; 7.99; 8.18; 9.48; 9.35
SECONDARY
Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights (MRCmax) of Metabolite AR-C124910XX.
0.300; 0.277; 0.286; 0.271
SECONDARY
Ratio of Metabolite AUC(0-t) to Parent AUC(0-t), Adjusted for Differences in Molecular Weights (MRAUC[0-t]) of Metabolite AR-C124910XX.
0.393; 0.380; 0.379; 0.371
SECONDARY
Ratio of Metabolite AUC [0-∞] to Parent AUC [0-∞], Adjusted for Differences in Molecular Weights (MRAUC [0-∞]) of Metabolite AR-C124910XX.
0.405; 0.391; 0.391; 0.382
SECONDARY
Percentage of Participants With Adverse Events (AEs).
9.7; 15.6; 8.8; 6.1; 0; 0
SECONDARY
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP).
-2; -2; -1; 3; 0; 1
SECONDARY
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
0; -1; -1; 0; 1; -1
SECONDARY
Participants With Significant Findings in 12-Lead Electrocardiography (ECG).
0; 0; 0; 0
SECONDARY
Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis.
0; 0; 0; 0

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 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02400333). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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