Trial Outcomes & Findings for Study to Assess the Bioequivalence Between Ticagrelor Orodispersible Tablets and Ticagrelor Immediate-release Tablets in Japanese Subjects (NCT NCT02436577)
NCT ID: NCT02436577
Last Updated: 2017-01-11
Results Overview
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).
COMPLETED
PHASE1
51 participants
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.
2017-01-11
Participant Flow
This study was conducted at PAREXEL International, Early Phase Clinical Unit London, Middlesex, United Kingdom.
Participants were randomized to a 6 sequence Williams square design for 3 periods and 3 treatments: 90 mg ticagrelor orodispersible (OD) tablet with water (Treatment A); 90 mg ticagrelor OD tablet without water (Treatment B); 90 mg ticagrelor immediate-release (IR) tablet with water (Treatment C).
Participant milestones
| Measure |
ABC Sequence
Subjects were administered a single dose of Treatment A, B and C as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
BCA Sequence
Subjects were administered a single dose of Treatment B, C and A as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
CAB Sequence
Subjects were administered a single dose of Treatment C, A and B as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
ACB Sequence
Subjects were administered a single dose of Treatment A, C and B as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
BAC Sequence
Subjects were administered a single dose of Treatment B, A and C as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
CBA Sequence
Subjects were administered a single dose of Treatment C, B and A as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
7
|
7
|
7
|
7
|
7
|
7
|
|
Overall Study
COMPLETED
|
7
|
6
|
7
|
7
|
7
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
ABC Sequence
Subjects were administered a single dose of Treatment A, B and C as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
BCA Sequence
Subjects were administered a single dose of Treatment B, C and A as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
CAB Sequence
Subjects were administered a single dose of Treatment C, A and B as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
ACB Sequence
Subjects were administered a single dose of Treatment A, C and B as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
BAC Sequence
Subjects were administered a single dose of Treatment B, A and C as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
CBA Sequence
Subjects were administered a single dose of Treatment C, B and A as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
|---|---|---|---|---|---|---|
|
Overall Study
Protocol Deviation
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Study to Assess the Bioequivalence Between Ticagrelor Orodispersible Tablets and Ticagrelor Immediate-release Tablets in Japanese Subjects
Baseline characteristics by cohort
| Measure |
ABC Sequence
n=7 Participants
Subjects were administered a single dose of Treatment A, B and C as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
BCA Sequence
n=7 Participants
Subjects were administered a single dose of Treatment B, C and A as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
CAB Sequence
n=7 Participants
Subjects were administered a single dose of Treatment C, A and B as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
ACB Sequence
n=7 Participants
Subjects were administered a single dose of Treatment A, C and B as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
BAC Sequence
n=7 Participants
Subjects were administered a single dose of Treatment B, A and C as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
CBA Sequence
n=7 Participants
Subjects were administered a single dose of Treatment C, B and A as first, second and third interventions (3 days each) respectively where each intervention is separated by the washout period of minimum 7 days.
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
28 years
STANDARD_DEVIATION 6 • n=5 Participants
|
32 years
STANDARD_DEVIATION 3 • n=7 Participants
|
32 years
STANDARD_DEVIATION 9 • n=5 Participants
|
32 years
STANDARD_DEVIATION 8 • n=4 Participants
|
31 years
STANDARD_DEVIATION 7 • n=21 Participants
|
29 years
STANDARD_DEVIATION 8 • n=10 Participants
|
31 years
STANDARD_DEVIATION 7 • n=115 Participants
|
|
Gender
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Gender
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
42 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Ticagrelor
|
529 ng/mL
Geometric Coefficient of Variation 38.4
|
534 ng/mL
Geometric Coefficient of Variation 29.8
|
569 ng/mL
Geometric Coefficient of Variation 37.0
|
|
Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
AR-C124910XX
|
165 ng/mL
Geometric Coefficient of Variation 31.4
|
158 ng/mL
Geometric Coefficient of Variation 36.5
|
170 ng/mL
Geometric Coefficient of Variation 35.5
|
PRIMARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
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
|
3462 h*ng/mL
Geometric Coefficient of Variation 43.8
|
3423 h*ng/mL
Geometric Coefficient of Variation 41.4
|
3546 h*ng/mL
Geometric Coefficient of Variation 45.0
|
|
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
|
1488 h*ng/mL
Geometric Coefficient of Variation 23.5
|
1441 h*ng/mL
Geometric Coefficient of Variation 24.5
|
1513 h*ng/mL
Geometric Coefficient of Variation 22.7
|
PRIMARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Ticagrelor
|
3520 ng*hr/mL
Geometric Coefficient of Variation 45.1
|
3485 ng*hr/mL
Geometric Coefficient of Variation 42.8
|
3606 ng*hr/mL
Geometric Coefficient of Variation 46.3
|
|
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC) of Ticagrelor and Its Active Metabolite AR-C124910XX.
AR-C124910XX
|
1547 ng*hr/mL
Geometric Coefficient of Variation 23.3
|
1503 ng*hr/mL
Geometric Coefficient of Variation 24.0
|
1573 ng*hr/mL
Geometric Coefficient of Variation 22.3
|
SECONDARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
AR-C124910XX
|
3.07 hours
Interval 2.0 to 6.0
|
3.00 hours
Interval 2.0 to 6.02
|
3.00 hours
Interval 1.0 to 8.0
|
|
Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Ticagrelor
|
3.00 hours
Interval 1.0 to 4.02
|
3.00 hours
Interval 1.02 to 5.97
|
2.00 hours
Interval 1.0 to 6.0
|
SECONDARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Ticagrelor
|
7.74 hours
Standard Deviation 1.19
|
7.94 hours
Standard Deviation 1.19
|
7.86 hours
Standard Deviation 1.09
|
|
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
|
9.13 hours
Standard Deviation 1.91
|
9.12 hours
Standard Deviation 1.81
|
9.05 hours
Standard Deviation 1.68
|
SECONDARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Terminal Elimination Rate Constant (λz) of Ticagrelor and Its Active Metabolite, AR-C124910XX.
Ticagrelor
|
0.0912 1/hour
Standard Deviation 0.0116
|
0.0889 1/hour
Standard Deviation 0.0116
|
0.0896 1/hour
Standard Deviation 0.0112
|
|
Terminal Elimination Rate Constant (λz) of Ticagrelor and Its Active Metabolite, AR-C124910XX.
AR-C124910XX
|
0.0792 1/hour
Standard Deviation 0.0170
|
0.0789 1/hour
Standard Deviation 0.0149
|
0.0794 1/hour
Standard Deviation 0.0160
|
SECONDARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Mean Residence Time (MRT) of Ticagrelor and Its Active Metabolite AR-C124910XX
Ticagrelor
|
9.66 hours
Standard Deviation 2.14
|
10.1 hours
Standard Deviation 2.32
|
9.68 hours
Standard Deviation 2.47
|
|
Mean Residence Time (MRT) of Ticagrelor and Its Active Metabolite AR-C124910XX
AR-C124910XX
|
13.3 hours
Standard Deviation 2.75
|
13.6 hours
Standard Deviation 2.90
|
13.2 hours
Standard Deviation 3.03
|
SECONDARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
MRCmax (Ratio of Metabolite Cmax to Parent Cmax, Adjusted for Differences in Molecular Weights) of Active Metabolite AR-C124910XX
|
0.340 ratio
Geometric Coefficient of Variation 41.4
|
0.322 ratio
Geometric Coefficient of Variation 44.8
|
0.327 ratio
Geometric Coefficient of Variation 43.2
|
SECONDARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
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
|
0.469 ratio
Geometric Coefficient of Variation 42.3
|
0.460 ratio
Geometric Coefficient of Variation 43.1
|
0.466 ratio
Geometric Coefficient of Variation 44.0
|
SECONDARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Ratio of Metabolite AUC to Parent AUC, Adjusted for Differences in Molecular Weights (MRAUC) of Active Metabolite AR-C124910XX
|
0.480 ratio
Geometric Coefficient of Variation 41.8
|
0.471 ratio
Geometric Coefficient of Variation 42.9
|
0.476 ratio
Geometric Coefficient of Variation 43.6
|
SECONDARY outcome
Timeframe: 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).Population: 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.
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.
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Participants with any AE
|
3 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events (AEs)
Participants with SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Elimination Rate Constant (Kel) of Ticagrelor and Its Active Metabolite AR-C124910XX
Ticagrelor
|
0.0904 1/hour
Standard Deviation 1.15
|
0.0881 1/hour
Standard Deviation 1.15
|
0.0889 1/hour
Standard Deviation 1.14
|
|
Elimination Rate Constant (Kel) of Ticagrelor and Its Active Metabolite AR-C124910XX
AR-C124910XX
|
0.0775 1/hour
Standard Deviation 1.23
|
0.0775 1/hour
Standard Deviation 1.21
|
0.0779 1/hour
Standard Deviation 1.21
|
SECONDARY outcome
Timeframe: Day 1 (pre dose, 2 hours, and 4 hours post dose) and Day 2 (24 hours post dose).Population: 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.
The following variables were collected after the participants had rested in the supine position for at least 5 minutes: SBP and DBP.
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP)
SBP: Day 1, 2 hours post dose
|
0 mmHg
Standard Deviation 8
|
0 mmHg
Standard Deviation 7
|
0 mmHg
Standard Deviation 8
|
|
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP)
SBP: Day 1, 4 hours post dose
|
3 mmHg
Standard Deviation 8
|
0 mmHg
Standard Deviation 8
|
3 mmHg
Standard Deviation 7
|
|
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP)
SBP: Day 2, 24 hours post dose
|
2 mmHg
Standard Deviation 8
|
1 mmHg
Standard Deviation 7
|
1 mmHg
Standard Deviation 8
|
|
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP)
DBP: Day 1, 2 hours post dose
|
-3 mmHg
Standard Deviation 5
|
-2 mmHg
Standard Deviation 6
|
-2 mmHg
Standard Deviation 6
|
|
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP)
DBP: Day 1, 4 hours post dose
|
-1 mmHg
Standard Deviation 6
|
0 mmHg
Standard Deviation 5
|
-1 mmHg
Standard Deviation 6
|
|
Mean Change From Baseline for Vital Signs of Supine Blood Pressure (SBP) and Diastolic BP (DBP)
DBP: Day 2, 24 hours post dose
|
1 mmHg
Standard Deviation 6
|
1 mmHg
Standard Deviation 6
|
-2 mmHg
Standard Deviation 6
|
SECONDARY outcome
Timeframe: 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.Population: 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.
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.
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Day 1, 2 hours post dose
|
1 bpm
Standard Deviation 5
|
3 bpm
Standard Deviation 7
|
1 bpm
Standard Deviation 4
|
|
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Day 1, 4 hours post dose
|
2 bpm
Standard Deviation 6
|
4 bpm
Standard Deviation 6
|
4 bpm
Standard Deviation 6
|
|
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Day 2, 24 hours post dose
|
1 bpm
Standard Deviation 5
|
2 bpm
Standard Deviation 5
|
1 bpm
Standard Deviation 4
|
SECONDARY outcome
Timeframe: At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart).Population: 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.
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.
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Participants With Significant Findings in 12-Lead Electrocardiography (ECG).
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: At Screening and at Follow-up (these two examinations are 7 to 8 weeks apart).Population: 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.
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).
Outcome measures
| Measure |
Treatment A
n=41 Participants
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.
|
Treatment B
n=41 Participants
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.
|
Treatment C
n=41 Participants
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis.
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Treatment A
Treatment B
Treatment C
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=41 participants at risk
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.
|
Treatment B
n=41 participants at risk
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.
|
Treatment C
n=41 participants at risk
Participants received Ticagrelor IR tablets administered orally with 150 mL of water.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
2.4%
1/41 • Number of events 1 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
4.9%
2/41 • Number of events 2 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
|
Nervous system disorders
Dizziness
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
2.4%
1/41 • Number of events 1 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
2.4%
1/41 • Number of events 1 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
|
Nervous system disorders
Headache
|
4.9%
2/41 • Number of events 2 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
|
Nervous system disorders
Presyncope
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
2.4%
1/41 • Number of events 1 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
4.9%
2/41 • Number of events 2 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
2.4%
1/41 • Number of events 1 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
|
General disorders
Feeling hot
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
2.4%
1/41 • Number of events 1 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
|
General disorders
Pyrexia
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
2.4%
1/41 • Number of events 1 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
|
Infections and infestations
Infected bites
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
0.00%
0/41 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
2.4%
1/41 • Number of events 1 • From the date of signing of informed consent (Day -28) up to 5-10 days after last administration of IMP (approximately 7-8 weeks).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a publication (e.g., in a scientific journal) based on the results of this study is envisaged, approval from AstraZeneca will be obtained and a draft manuscript will be submitted to AstraZeneca for scrutiny and comment. The choice of conduit will be mutually agreed on by the Principal Investigator and AstraZeneca.
- Publication restrictions are in place
Restriction type: OTHER