| Primary | 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). | The pharmacokinetic (PK) analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with saliva. | | OG002 | Treatment C | Participants received Ticagrelor IR tablets administered orally with 150 mL of water. |
| | | Title | Denominators | Categories |
|---|
| Ticagrelor | | | Title | Measurements |
|---|
| - OG000529± 38.4
- OG001534± 29.8
- OG002569± 37.0
|
| | AR-C124910XX |
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| Statistical Assessment of Bioequivalence for Ticagrelor Following Ticagrelor OD Tablets Compared to Ticagrelor IR Tablets. | ANOVA | | | | Geometric Mean Ratio | 93.16 | | | 2-Sided | 90 | 85.80 | 101.15 | | | | No | Superiority or Other | | | | Statistical Assessment of Bioequivalence for Ticagrelor Following Ticagrelor OD Tablets Compared to Ticagrelor IR Tablets. |
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| 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. | 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 |
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| Primary | 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | |
|
| Secondary | Time to Reach Maximum Observed Concentration (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. 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Median | Full Range | hours | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with saliva. |
|
| Secondary | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX. | Comparison of t½λz (half-life associated with terminal slope (λz) 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. 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Mean | Standard Deviation | hours | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B |
|
| Secondary | Terminal Elimination Rate Constant (λz) of Ticagrelor and Its Active Metabolite, AR-C124910XX. | Comparison of terminal elimination rate constant (λz) 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Mean | Standard Deviation | 1/hour | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with saliva. |
|
| Secondary | 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. 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Geometric Mean | Standard Deviation | hours | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with saliva. |
|
| Secondary | MRCmax (Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights) of 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. 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ratio | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B |
|
| Secondary | Ratio of Metabolite AUC(0-t) to Parent AUC(0-t), Adjusted for Differences in Molecular Weights (MRAUC [0-t]) of 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. 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ratio | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B |
|
| Secondary | Ratio of Metabolite AUC to Parent AUC, Adjusted for Differences in Molecular Weights (MRAUC) of 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. 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ratio | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | |
|
| Secondary | Number 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. | The safety analysis set included all participants who received at least 1 dose of ticagrelor and for whom any safety post-dose data were available. | Posted | | Number | | Participants | | From the date of randomization (Day 1 of the first treatment period) until the final follow-up visit (5 to 10 days after last administration of IMP). | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B |
|
| Secondary | Elimination Rate Constant (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. 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). | The PK analysis set consisted of all participants for whom at least 1 of the primary PK parameters, for a given analyte, was calculated for at least 2 treatment periods (where 1 of the treatment periods was the period in which the participant received the reference product [Treatment C]) and who had no major protocol deviations. | Posted | | Geometric Mean | Standard Deviation | 1/hour | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with saliva. |
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| 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. | The safety analysis set included all participants who received at least 1 dose of ticagrelor and for whom any safety post-dose data were available. | Posted | | Mean | Standard Deviation | mmHg | | Day 1 (pre dose, 2 hours, and 4 hours post dose) and Day 2 (24 hours post dose). | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with saliva. | | OG002 | Treatment C | Participants received Ticagrelor IR tablets administered orally with 150 mL of water. |
| |
| Secondary | Mean Change From Baseline for Vital Signs in Supine Pulse Rate. | Vital signs i.e. Pulse (beats per minute [bpm]) were collected after the participant has rested in the supine position for at least 5 minutes. | The safety analysis set included all participants who received at least 1 dose of ticagrelor and for whom any safety post-dose data were available. | Posted | | Mean | Standard Deviation | bpm | | 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. | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with saliva. | | OG002 | Treatment C | Participants received Ticagrelor IR tablets administered orally with 150 mL of water. |
|
| 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. | The safety analysis set included all participants who received at least 1 dose of ticagrelor and for whom any safety post-dose data were available. | Posted | | Number | | participants | | At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart). | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with saliva. | | OG002 | Treatment C | Participants received Ticagrelor IR tablets administered orally with 150 mL of water. |
|
| 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). | The safety analysis set included all participants who received at least 1 dose of ticagrelor and for whom any safety post-dose data were available. | Posted | | Number | | participants | | At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart). | | | | ID | Title | Description |
|---|
| OG000 | Treatment A | Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with 150 mL non-carbonated water at room temperature. | | OG001 | Treatment B | Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed with dry hands on the tongue for disintegration and was swallowed subsequently with saliva. | | OG002 |
|