Bioavailability, Healthy Subjects
Conditions
Keywords
ticagrelor orodispersible tablet, ticagrelor immediate-release tablet, relative bioavailability, Phase I, healthy subjects
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
Detailed 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.
Interventions
DRUGTicagrelor OD tablet (90 mg single dose) administered with 200 ml of water
90 mg single dose
90 mg single dose
DRUGTicagrelor OD tablet (90 mg single dose) suspended in water administered via nasogastric tube
90 mg single dose
DRUGBrilique®, Ticagrelor IR tablet (90 mg) administered with 200mL of water
90 mg single dose
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) 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. | 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). |
| 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. | 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. | 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). |
| Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]). | 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. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| 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. | Assesssment of MRAUC \[0-∞\] (Ratio of metabolite AUC \[0-∞\] to parent AUC \[0-∞\], 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. |
| Percentage of Participants With Adverse Events (AEs). | SAEs were recorded from the signing of informed consent and AEs were recorded from randomisation until the final follow-up visit. | An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The term AE is used generally to include any AE whether serious or non-serious. A serious AE (SAE) is an AE that fulfills one or more of the following criteria: results in death, is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. |
| 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. | 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). |
| Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 1 (2, 4 hours post-dose) and Day 2 (24 hours post-dose). | Vital signs were collected after the participant has rested in the supine position for at least 5 minutes. |
| Participants With Significant Findings in 12-Lead Electrocardiography (ECG). | At screening and at follow-up. | A 12-lead ECG was obtained after the participant rested in supine position for at least 10 minutes. The study physician was to judge the overall interpretation as normal or abnormal. If abnormal, it was decided as to whether or not the abnormality was clinically significant and the reason for the abnormality was recorded. |
| Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis. | At screening, at admission on Day -1 to each treatment period and at follow-up. | Participants were assessed through each laboratory variables for any significant abnormalities. Hematology assessments included white blood cell count, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and others. Clinical chemistry assessment included testing levels of sodium, potassium, urea, creatinine, albumin, calcium, glucose (fasting) and others. Urinalysis assessment included glucose, protein, blood and microscopy (if positive for blood or protein). |
| Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | Day 1 (2, 4 hours post-dose) and Day 2 (24 hours post-dose). | The following variables were collected after the participants had rested in the supine position for at least 5 minutes: SBP and DBP. |
| 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. | 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). |
| 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. | 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. |
Countries
Germany
Participant flow
Recruitment details
This study was conducted at PAREXEL International, Early Phase Clinical Unit Berlin, Berlin, Germany. In this study, 100 participants were screened, out of which 36 were randomized and treated.
Pre-assignment details
Participants were randomized in 4 sequence Williams design for 4 periods and 4 treatments:Ticagrelor orodispersible (OD) tablets with water (Treatment A);Ticagrelor OD tablets without water (Treatment B);Ticagrelor OD tablets suspended in water through nasogastric tube (Treatment C);Ticagrelor immediate-release (IR) tablets with water(Treatment D).
Participants by arm
| Arm | Count |
|---|---|
| ADBC Sequence Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4. | 9 |
| BACD Sequence Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4. | 9 |
| CBDA Sequence Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4. | 9 |
| DCAB Sequence Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4. | 9 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | ADBC Sequence | BACD Sequence | CBDA Sequence | DCAB Sequence | Total |
|---|---|---|---|---|---|
| Age, Continuous | 42 years STANDARD_DEVIATION 12 | 44 years STANDARD_DEVIATION 12 | 42 years STANDARD_DEVIATION 13 | 40 years STANDARD_DEVIATION 13 | 42 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 31 | 5 / 32 | 3 / 34 | 2 / 33 |
| serious Total, serious adverse events | 0 / 31 | 0 / 32 | 0 / 34 | 0 / 33 |
Outcome results
Primary
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).
Time frame: 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.
Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one of the primary PK parameters, for a given analyte, can be calculated for at least two treatment periods and who had no major protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]). | Ticagrelor | 3068 h·ng/mL | Geometric Coefficient of Variation 29.2 |
| Treatment A | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]). | AR-C124910XX | 1138 h·ng/mL | Geometric Coefficient of Variation 19.1 |
| Treatment B | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]). | AR-C124910XX | 1155 h·ng/mL | Geometric Coefficient of Variation 20.7 |
| Treatment B | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]). | Ticagrelor | 3228 h·ng/mL | Geometric Coefficient of Variation 44.2 |
| Treatment C | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]). | Ticagrelor | 3226 h·ng/mL | Geometric Coefficient of Variation 42.9 |
| Treatment C | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]). | AR-C124910XX | 1154 h·ng/mL | Geometric Coefficient of Variation 23.6 |
| Treatment D | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]). | Ticagrelor | 3423 h·ng/mL | Geometric Coefficient of Variation 41.8 |
| Treatment D | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]). | AR-C124910XX | 1197 h·ng/mL | Geometric Coefficient of Variation 22.5 |
Comparison: Statistical assessment of ticagrelor relative bioavailability following ticagrelor OD tablets administered with water compared to ticagrelor IR tablets.95% CI: [90.27, 99.89]
Comparison: Statistical assessment of ticagrelor relative bioavailability following ticagrelor OD tablets administered without water compared to ticagrelor IR tablets.95% CI: [89.81, 100.99]
Comparison: Statistical assessment of ticagrelor relative bioavailability following ticagrelor OD tablets suspended in water and administered through NG tube compared to ticagrelor IR tablets.95% CI: [90.26, 98.73]
Comparison: Statistical assessment of metabolite AR-C124910XX relative bioavailability following ticagrelor OD tablets administered with water compared to ticagrelor IR tablets.95% CI: [91.36, 98.42]
Comparison: Statistical assessment of metabolite AR-C124910XX relative bioavailability following ticagrelor OD tablets administered without water compared to ticagrelor IR tablets.95% CI: [91.78, 99.82]
Comparison: Statistical assessment of metabolite AR-C124910XX relative bioavailability following ticagrelor OD tablets suspended in water and administered through NG tube compared to ticagrelor IR tablets.95% CI: [93.26, 99.87]
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.
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).
Time frame: 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.
Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one of the primary PK parameters, for a given analyte, can be calculated for at least two treatment periods and who had no major protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | 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. | Ticagrelor | 3023 h·ng/mL | Geometric Coefficient of Variation 28.6 |
| Treatment A | 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. | AR-C124910XX | 1087 h·ng/mL | Geometric Coefficient of Variation 19.7 |
| Treatment B | 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. | AR-C124910XX | 1104 h·ng/mL | Geometric Coefficient of Variation 20.7 |
| Treatment B | 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. | Ticagrelor | 3172 h·ng/mL | Geometric Coefficient of Variation 42.6 |
| Treatment C | 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. | Ticagrelor | 3174 h·ng/mL | Geometric Coefficient of Variation 40.9 |
| Treatment C | 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. | AR-C124910XX | 1101 h·ng/mL | Geometric Coefficient of Variation 24.4 |
| Treatment D | 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. | Ticagrelor | 3358 h·ng/mL | Geometric Coefficient of Variation 40 |
| Treatment D | 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. | AR-C124910XX | 1140 h·ng/mL | Geometric Coefficient of Variation 23 |
Comparison: Statistical assessment of ticagrelor relative bioavailability following ticagrelor OD tablets administered with water compared to ticagrelor IR tablets.95% CI: [90.33, 99.99]
Comparison: Statistical assessment of ticagrelor relative bioavailability following ticagrelor OD tablets administered without water compared to ticagrelor IR tablets.95% CI: [89.94, 101.21]
Comparison: Statistical assessment of ticagrelor relative bioavailability following ticagrelor OD tablets suspended in water and administered through NG tube compared to ticagrelor IR tablets.95% CI: [90.53, 98.98]
Comparison: Statistical assessment of metabolite AR-C124910XX relative bioavailability following ticagrelor OD tablets administered with water compared to ticagrelor IR tablets.95% CI: [90.94, 98.56]
Comparison: Statistical assessment of metabolite AR-C124910XX relative bioavailability following ticagrelor OD tablets administered without water compared to ticagrelor IR tablets.95% CI: [91.87, 100.33]
Comparison: Statistical assessment of metabolite AR-C124910XX relative bioavailability following ticagrelor OD tablets suspended in water and administered through NG tube compared to ticagrelor IR tablets.95% CI: [93.08, 100.17]
Primary
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).
Time frame: 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.
Population: The Pharmacokinetic (PK) analysis set consisted of all participants in the safety analysis set for whom at least one of the primary PK parameters, for a given analyte, can be calculated for at least two treatment periods and who had no major protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 428 ng/mL | Geometric Coefficient of Variation 25 |
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 118 ng/mL | Geometric Coefficient of Variation 26.5 |
| Treatment B | Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 126 ng/mL | Geometric Coefficient of Variation 24.7 |
| Treatment B | Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 499 ng/mL | Geometric Coefficient of Variation 34 |
| Treatment C | Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 479 ng/mL | Geometric Coefficient of Variation 32.1 |
| Treatment C | Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 126 ng/mL | Geometric Coefficient of Variation 30.4 |
| Treatment D | Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 520 ng/mL | Geometric Coefficient of Variation 29 |
| Treatment D | Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 129 ng/mL | Geometric Coefficient of Variation 31.8 |
Comparison: Statistical assessment of ticagrelor relative bioavailability following ticagrelor OD tablets administered with water compared to ticagrelor IR tablets.90% CI: [76.77, 93.78]
Comparison: Statistical assessment of ticagrelor relative bioavailability following ticagrelor OD tablets administered without water compared to ticagrelor IR tablets.95% CI: [88.22, 105.79]
Comparison: Statistical assessment of ticagrelor relative bioavailability following ticagrelor OD tablets suspended in water and administered through NG tube compared to ticagrelor IR tablets.95% CI: [85.59, 99.25]
Comparison: Statistical assessment of metabolite AR-C124910XX relative bioavailability following ticagrelor OD tablets administered with water compared to ticagrelor IR tablets.95% CI: [82.03, 98.39]
Comparison: Statistical assessment of metabolite AR-C124910XX relative bioavailability following ticagrelor OD tablets administered without water compared to ticagrelor IR tablets.95% CI: [90.53, 104.9]
Comparison: Statistical assessment of metabolite AR-C124910XX relative bioavailability following ticagrelor OD tablets suspended in water and administered through NG tube compared to ticagrelor IR tablets.95% CI: [90.83, 103.74]
Secondary
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) 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).
Time frame: 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.
Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one of the primary PK parameters, for a given analyte, can be calculated for at least two treatment periods and who had no major protocol deviations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 8.02 h | Standard Deviation 1.25 |
| Treatment A | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 9.48 h | Standard Deviation 1.43 |
| Treatment B | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 9.35 h | Standard Deviation 1.81 |
| Treatment B | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 8.21 h | Standard Deviation 1.46 |
| Treatment C | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 7.99 h | Standard Deviation 1.83 |
| Treatment C | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 9.36 h | Standard Deviation 2.18 |
| Treatment D | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 8.18 h | Standard Deviation 1.71 |
| Treatment D | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 9.47 h | Standard Deviation 2.02 |
Secondary
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Vital signs were collected after the participant has rested in the supine position for at least 5 minutes.
Time frame: Day 1 (2, 4 hours post-dose) and Day 2 (24 hours post-dose).
Population: The safety analysis set included all participants who received at least one dose of ticagrelor and for whom any safety post-dose data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 1, 2h Post-dose | 0 bpm | Standard Deviation 5 |
| Treatment A | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 2, 24h Post-dose | 0 bpm | Standard Deviation 6 |
| Treatment A | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 1, 4 Post-dose | 1 bpm | Standard Deviation 6 |
| Treatment B | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 1, 2h Post-dose | -1 bpm | Standard Deviation 5 |
| Treatment B | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 2, 24h Post-dose | 1 bpm | Standard Deviation 7 |
| Treatment B | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 1, 4 Post-dose | -1 bpm | Standard Deviation 6 |
| Treatment C | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 1, 4 Post-dose | -1 bpm | Standard Deviation 7 |
| Treatment C | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 1, 2h Post-dose | -1 bpm | Standard Deviation 6 |
| Treatment C | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 2, 24h Post-dose | 1 bpm | Standard Deviation 7 |
| Treatment D | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 1, 2h Post-dose | 0 bpm | Standard Deviation 5 |
| Treatment D | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 2, 24h Post-dose | 1 bpm | Standard Deviation 7 |
| Treatment D | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Day 1, 4 Post-dose | 2 bpm | Standard Deviation 5 |
Secondary
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP).
The following variables were collected after the participants had rested in the supine position for at least 5 minutes: SBP and DBP.
Time frame: Day 1 (2, 4 hours post-dose) and Day 2 (24 hours post-dose).
Population: The safety analysis set included all participants who received at least one dose of ticagrelor and for whom any safety post-dose data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 1, 2h Post-dose | -2 mmHg | Standard Deviation 8 |
| Treatment A | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 1, 2h Post-dose | -1 mmHg | Standard Deviation 6 |
| Treatment A | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 1, 4 Post-dose | 0 mmHg | Standard Deviation 5 |
| Treatment A | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 1, 4 Post-dose | 0 mmHg | Standard Deviation 9 |
| Treatment A | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 2, 24h Post-dose | 0 mmHg | Standard Deviation 6 |
| Treatment A | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 2, 24h Post-dose | -2 mmHg | Standard Deviation 6 |
| Treatment B | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 2, 24h Post-dose | -1 mmHg | Standard Deviation 9 |
| Treatment B | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 1, 4 Post-dose | -1 mmHg | Standard Deviation 4 |
| Treatment B | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 1, 4 Post-dose | 1 mmHg | Standard Deviation 8 |
| Treatment B | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 1, 2h Post-dose | -1 mmHg | Standard Deviation 5 |
| Treatment B | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 1, 2h Post-dose | -2 mmHg | Standard Deviation 7 |
| Treatment B | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 2, 24h Post-dose | -3 mmHg | Standard Deviation 5 |
| Treatment C | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 2, 24h Post-dose | -3 mmHg | Standard Deviation 6 |
| Treatment C | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 1, 2h Post-dose | -4 mmHg | Standard Deviation 6 |
| Treatment C | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 1, 2h Post-dose | -1 mmHg | Standard Deviation 8 |
| Treatment C | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 1, 4 Post-dose | -1 mmHg | Standard Deviation 9 |
| Treatment C | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 2, 24h Post-dose | -3 mmHg | Standard Deviation 8 |
| Treatment C | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 1, 4 Post-dose | -3 mmHg | Standard Deviation 5 |
| Treatment D | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 2, 24h Post-dose | 1 mmHg | Standard Deviation 10 |
| Treatment D | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 2, 24h Post-dose | -1 mmHg | Standard Deviation 6 |
| Treatment D | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 1, 4 Post-dose | 0 mmHg | Standard Deviation 5 |
| Treatment D | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 1, 4 Post-dose | 2 mmHg | Standard Deviation 8 |
| Treatment D | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | SBP - Day 1, 2h Post-dose | 3 mmHg | Standard Deviation 8 |
| Treatment D | Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP). | DBP - Day 1, 2h Post-dose | 0 mmHg | Standard Deviation 5 |
Secondary
Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis.
Participants were assessed through each laboratory variables for any significant abnormalities. Hematology assessments included white blood cell count, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and others. Clinical chemistry assessment included testing levels of sodium, potassium, urea, creatinine, albumin, calcium, glucose (fasting) and others. Urinalysis assessment included glucose, protein, blood and microscopy (if positive for blood or protein).
Time frame: At screening, at admission on Day -1 to each treatment period and at follow-up.
Population: The safety analysis set included all participants who received at least one dose of ticagrelor and for whom any safety post-dose data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A | Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis. | 0 participants |
| Treatment B | Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis. | 0 participants |
| Treatment C | Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis. | 0 participants |
| Treatment D | Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis. | 0 participants |
Secondary
Participants With Significant Findings in 12-Lead Electrocardiography (ECG).
A 12-lead ECG was obtained after the participant rested in supine position for at least 10 minutes. The study physician was to judge the overall interpretation as normal or abnormal. If abnormal, it was decided as to whether or not the abnormality was clinically significant and the reason for the abnormality was recorded.
Time frame: At screening and at follow-up.
Population: The safety analysis set included all participants who received at least one dose of ticagrelor and for whom any safety post-dose data were available.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Treatment A | Participants With Significant Findings in 12-Lead Electrocardiography (ECG). | 0 participants | 6 |
| Treatment B | Participants With Significant Findings in 12-Lead Electrocardiography (ECG). | 0 participants | 7 |
| Treatment C | Participants With Significant Findings in 12-Lead Electrocardiography (ECG). | 0 participants | 7 |
| Treatment D | Participants With Significant Findings in 12-Lead Electrocardiography (ECG). | 0 participants | 7 |
Secondary
Percentage of Participants With Adverse Events (AEs).
An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The term AE is used generally to include any AE whether serious or non-serious. A serious AE (SAE) is an AE that fulfills one or more of the following criteria: results in death, is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above.
Time frame: SAEs were recorded from the signing of informed consent and AEs were recorded from randomisation until the final follow-up visit.
Population: The safety analysis set included all participants who received at least one dose of ticagrelor and for whom any safety post-dose data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Percentage of Participants With Adverse Events (AEs). | AEs | 9.7 percentage of participants |
| Treatment A | Percentage of Participants With Adverse Events (AEs). | SAEs | 0 percentage of participants |
| Treatment B | Percentage of Participants With Adverse Events (AEs). | SAEs | 0 percentage of participants |
| Treatment B | Percentage of Participants With Adverse Events (AEs). | AEs | 15.6 percentage of participants |
| Treatment C | Percentage of Participants With Adverse Events (AEs). | AEs | 8.8 percentage of participants |
| Treatment C | Percentage of Participants With Adverse Events (AEs). | SAEs | 0 percentage of participants |
| Treatment D | Percentage of Participants With Adverse Events (AEs). | AEs | 6.1 percentage of participants |
| Treatment D | Percentage of Participants With Adverse Events (AEs). | SAEs | 0 percentage of participants |
Secondary
Ratio of Metabolite AUC [0-∞] to Parent AUC [0-∞], Adjusted for Differences in Molecular Weights (MRAUC [0-∞]) of Metabolite AR-C124910XX.
Assesssment of MRAUC \[0-∞\] (Ratio of metabolite AUC \[0-∞\] to parent AUC \[0-∞\], 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.
Time frame: 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.
Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one of the primary PK parameters, for a given analyte, can be calculated for at least two treatment periods and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Ratio of Metabolite AUC [0-∞] to Parent AUC [0-∞], Adjusted for Differences in Molecular Weights (MRAUC [0-∞]) of Metabolite AR-C124910XX. | 0.405 ratio | Geometric Coefficient of Variation 30 |
| Treatment B | Ratio of Metabolite AUC [0-∞] to Parent AUC [0-∞], Adjusted for Differences in Molecular Weights (MRAUC [0-∞]) of Metabolite AR-C124910XX. | 0.391 ratio | Geometric Coefficient of Variation 42.4 |
| Treatment C | Ratio of Metabolite AUC [0-∞] to Parent AUC [0-∞], Adjusted for Differences in Molecular Weights (MRAUC [0-∞]) of Metabolite AR-C124910XX. | 0.391 ratio | Geometric Coefficient of Variation 42.2 |
| Treatment D | Ratio of Metabolite AUC [0-∞] to Parent AUC [0-∞], Adjusted for Differences in Molecular Weights (MRAUC [0-∞]) of Metabolite AR-C124910XX. | 0.382 ratio | Geometric Coefficient of Variation 43.1 |
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.
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.
Time frame: 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.
Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one of the primary PK parameters, for a given analyte, can be calculated for at least two treatment periods and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | 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 ratio | Geometric Coefficient of Variation 29.8 |
| Treatment B | Ratio of Metabolite AUC(0-t) to Parent AUC(0-t), Adjusted for Differences in Molecular Weights (MRAUC[0-t]) of Metabolite AR-C124910XX. | 0.380 ratio | Geometric Coefficient of Variation 42.7 |
| Treatment C | Ratio of Metabolite AUC(0-t) to Parent AUC(0-t), Adjusted for Differences in Molecular Weights (MRAUC[0-t]) of Metabolite AR-C124910XX. | 0.379 ratio | Geometric Coefficient of Variation 43.2 |
| Treatment D | Ratio of Metabolite AUC(0-t) to Parent AUC(0-t), Adjusted for Differences in Molecular Weights (MRAUC[0-t]) of Metabolite AR-C124910XX. | 0.371 ratio | Geometric Coefficient of Variation 43.4 |
Secondary
Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights (MRCmax) of 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.
Time frame: 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.
Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one of the primary PK parameters, for a given analyte, can be calculated for at least two treatment periods and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights (MRCmax) of Metabolite AR-C124910XX. | 0.300 ratio | Geometric Coefficient of Variation 27.5 |
| Treatment B | Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights (MRCmax) of Metabolite AR-C124910XX. | 0.277 ratio | Geometric Coefficient of Variation 40.1 |
| Treatment C | Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights (MRCmax) of Metabolite AR-C124910XX. | 0.286 ratio | Geometric Coefficient of Variation 33.3 |
| Treatment D | Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights (MRCmax) of Metabolite AR-C124910XX. | 0.271 ratio | Geometric Coefficient of Variation 32.6 |
Secondary
Time to Reach Maximum Observed Concentration (Tmax) 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).
Time frame: 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.
Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one of the primary PK parameters, for a given analyte, can be calculated for at least two treatment periods and who had no major protocol deviations.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A | Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 2.02 h |
| Treatment A | Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 3.00 h |
| Treatment B | Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 3.00 h |
| Treatment B | Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 2.00 h |
| Treatment C | Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 2.00 h |
| Treatment C | Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 2.00 h |
| Treatment D | Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Ticagrelor | 2.00 h |
| Treatment D | Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX. | AR-C124910XX | 2.00 h |