Trial Outcomes & Findings for Study to Assess the Bioavailability of Ticagrelor OD Tablet vs. IR Tablet (NCT NCT02400333)
NCT ID: NCT02400333
Last Updated: 2016-09-29
Results Overview
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).
COMPLETED
PHASE1
100 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.
2016-09-29
Participant Flow
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.
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).
Participant milestones
| Measure |
ADBC Sequence
Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4.
|
BACD Sequence
Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4.
|
CBDA Sequence
Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4.
|
DCAB Sequence
Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
9
|
9
|
|
Overall Study
COMPLETED
|
8
|
8
|
7
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
2
|
2
|
Reasons for withdrawal
| Measure |
ADBC Sequence
Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4.
|
BACD Sequence
Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4.
|
CBDA Sequence
Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4.
|
DCAB Sequence
Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
2
|
1
|
Baseline Characteristics
Study to Assess the Bioavailability of Ticagrelor OD Tablet vs. IR Tablet
Baseline characteristics by cohort
| Measure |
ADBC Sequence
n=9 Participants
Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4.
|
BACD Sequence
n=9 Participants
Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4.
|
CBDA Sequence
n=9 Participants
Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4.
|
DCAB Sequence
n=9 Participants
Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4.
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
42 years
STANDARD_DEVIATION 12 • n=5 Participants
|
44 years
STANDARD_DEVIATION 12 • n=7 Participants
|
42 years
STANDARD_DEVIATION 13 • n=5 Participants
|
40 years
STANDARD_DEVIATION 13 • n=4 Participants
|
42 years
STANDARD_DEVIATION 12 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
32 Participants
n=21 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 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.
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).
Outcome measures
| Measure |
Treatment A
n=30 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=31 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=33 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Ticagrelor
|
428 ng/mL
Geometric Coefficient of Variation 25.0
|
499 ng/mL
Geometric Coefficient of Variation 34.0
|
479 ng/mL
Geometric Coefficient of Variation 32.1
|
520 ng/mL
Geometric Coefficient of Variation 29.0
|
|
Maximum Observed Plasma Concentration (Cmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
AR-C124910XX
|
118 ng/mL
Geometric Coefficient of Variation 26.5
|
126 ng/mL
Geometric Coefficient of Variation 24.7
|
126 ng/mL
Geometric Coefficient of Variation 30.4
|
129 ng/mL
Geometric Coefficient of Variation 31.8
|
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 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.
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).
Outcome measures
| Measure |
Treatment A
n=30 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=31 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=33 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 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
|
3023 h·ng/mL
Geometric Coefficient of Variation 28.6
|
3172 h·ng/mL
Geometric Coefficient of Variation 42.6
|
3174 h·ng/mL
Geometric Coefficient of Variation 40.9
|
3358 h·ng/mL
Geometric Coefficient of Variation 40.0
|
|
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
|
1087 h·ng/mL
Geometric Coefficient of Variation 19.7
|
1104 h·ng/mL
Geometric Coefficient of Variation 20.7
|
1101 h·ng/mL
Geometric Coefficient of Variation 24.4
|
1140 h·ng/mL
Geometric Coefficient of Variation 23.0
|
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 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.
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).
Outcome measures
| Measure |
Treatment A
n=30 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=31 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=33 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]).
Ticagrelor
|
3068 h·ng/mL
Geometric Coefficient of Variation 29.2
|
3228 h·ng/mL
Geometric Coefficient of Variation 44.2
|
3226 h·ng/mL
Geometric Coefficient of Variation 42.9
|
3423 h·ng/mL
Geometric Coefficient of Variation 41.8
|
|
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC [0-∞]).
AR-C124910XX
|
1138 h·ng/mL
Geometric Coefficient of Variation 19.1
|
1155 h·ng/mL
Geometric Coefficient of Variation 20.7
|
1154 h·ng/mL
Geometric Coefficient of Variation 23.6
|
1197 h·ng/mL
Geometric Coefficient of Variation 22.5
|
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 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.
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).
Outcome measures
| Measure |
Treatment A
n=30 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=31 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=33 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
Ticagrelor
|
2.02 h
Interval 1.0 to 4.02
|
2.00 h
Interval 1.0 to 4.0
|
2.00 h
Interval 0.98 to 4.0
|
2.00 h
Interval 0.98 to 4.0
|
|
Time to Reach Maximum Observed Concentration (Tmax) of Ticagrelor and Its Active Metabolite AR-C124910XX.
AR-C124910XX
|
3.00 h
Interval 1.98 to 6.0
|
3.00 h
Interval 1.98 to 4.0
|
2.00 h
Interval 1.98 to 4.02
|
2.00 h
Interval 1.98 to 4.0
|
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 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.
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).
Outcome measures
| Measure |
Treatment A
n=30 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=31 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=33 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 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
|
8.02 h
Standard Deviation 1.25 • Interval 1.0 to 4.02
|
8.21 h
Standard Deviation 1.46 • Interval 1.0 to 4.0
|
7.99 h
Standard Deviation 1.83 • Interval 0.98 to 4.0
|
8.18 h
Standard Deviation 1.71 • Interval 0.98 to 4.0
|
|
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 • Interval 1.98 to 6.0
|
9.35 h
Standard Deviation 1.81 • Interval 1.98 to 4.0
|
9.36 h
Standard Deviation 2.18 • Interval 1.98 to 4.02
|
9.47 h
Standard Deviation 2.02 • Interval 1.98 to 4.0
|
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 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.
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.
Outcome measures
| Measure |
Treatment A
n=30 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=31 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=33 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
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 • Interval 1.98 to 6.0
|
0.277 ratio
Geometric Coefficient of Variation 40.1 • Interval 1.98 to 4.0
|
0.286 ratio
Geometric Coefficient of Variation 33.3 • Interval 1.98 to 4.02
|
0.271 ratio
Geometric Coefficient of Variation 32.6 • Interval 1.98 to 4.0
|
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 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.
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.
Outcome measures
| Measure |
Treatment A
n=30 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=31 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=33 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
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 • Interval 1.98 to 6.0
|
0.380 ratio
Geometric Coefficient of Variation 42.7 • Interval 1.98 to 4.0
|
0.379 ratio
Geometric Coefficient of Variation 43.2 • Interval 1.98 to 4.02
|
0.371 ratio
Geometric Coefficient of Variation 43.4 • Interval 1.98 to 4.0
|
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 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.
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.
Outcome measures
| Measure |
Treatment A
n=30 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=31 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=33 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
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 30.0 • Interval 1.98 to 6.0
|
0.391 ratio
Geometric Coefficient of Variation 42.4 • Interval 1.98 to 4.0
|
0.391 ratio
Geometric Coefficient of Variation 42.2 • Interval 1.98 to 4.02
|
0.382 ratio
Geometric Coefficient of Variation 43.1 • Interval 1.98 to 4.0
|
SECONDARY outcome
Timeframe: 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.
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=31 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=32 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=34 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
Percentage of Participants With Adverse Events (AEs).
AEs
|
9.7 percentage of participants
|
15.6 percentage of participants
|
8.8 percentage of participants
|
6.1 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs).
SAEs
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 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.
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=31 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=32 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=34 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
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
|
-2 mmHg
Standard Deviation 7
|
-1 mmHg
Standard Deviation 8
|
3 mmHg
Standard Deviation 8
|
|
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
|
1 mmHg
Standard Deviation 8
|
-1 mmHg
Standard Deviation 9
|
2 mmHg
Standard Deviation 8
|
|
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
|
-1 mmHg
Standard Deviation 9
|
-3 mmHg
Standard Deviation 8
|
1 mmHg
Standard Deviation 10
|
|
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
|
-1 mmHg
Standard Deviation 5
|
-4 mmHg
Standard Deviation 6
|
0 mmHg
Standard Deviation 5
|
|
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
|
-1 mmHg
Standard Deviation 4
|
-3 mmHg
Standard Deviation 5
|
0 mmHg
Standard Deviation 5
|
|
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
|
-3 mmHg
Standard Deviation 5
|
-3 mmHg
Standard Deviation 6
|
-1 mmHg
Standard Deviation 6
|
SECONDARY outcome
Timeframe: 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.
Vital signs were collected after the participant has rested in the supine position for at least 5 minutes.
Outcome measures
| Measure |
Treatment A
n=31 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=32 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=34 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Day 1, 2h Post-dose
|
0 bpm
Standard Deviation 5
|
-1 bpm
Standard Deviation 5
|
-1 bpm
Standard Deviation 6
|
0 bpm
Standard Deviation 5
|
|
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Day 1, 4 Post-dose
|
1 bpm
Standard Deviation 6
|
-1 bpm
Standard Deviation 6
|
-1 bpm
Standard Deviation 7
|
2 bpm
Standard Deviation 5
|
|
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Day 2, 24h Post-dose
|
0 bpm
Standard Deviation 6
|
1 bpm
Standard Deviation 7
|
1 bpm
Standard Deviation 7
|
1 bpm
Standard Deviation 7
|
SECONDARY outcome
Timeframe: 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.
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=31 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=32 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=34 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
Participants With Significant Findings in 12-Lead Electrocardiography (ECG).
|
0 participants
6
|
0 participants
7
|
0 participants
7
|
0 participants
7
|
SECONDARY outcome
Timeframe: 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.
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=31 Participants
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=32 Participants
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=34 Participants
Participants received Ticagrelor OD tablets suspended in water to be administered through a nasogastric tube (NG) tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 Participants
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
Participants With Clinically Significant Findings in Hematology, Clinical Chemistry and Urinalysis.
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Treatment A
Treatment B
Treatment C
Treatment D
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=31 participants at risk
Participants received Ticagrelor OD tablets administered with water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with 200 mL noncarbonated water at room temperature.
|
Treatment B
n=32 participants at risk
Participants received Ticagrelor OD tablets administered without water. The OD tablet was placed on the tongue to disintegrate and be swallowed subsequently with saliva.
|
Treatment C
n=34 participants at risk
Participants received Ticagrelor OD tablets suspended in water to be administered through a NG tube into the stomach (total of 200 mL of water).
|
Treatment D
n=33 participants at risk
Participants received Ticagrelor IR tablets administered orally with 200 mL of water.
|
|---|---|---|---|---|
|
Nervous system disorders
Dizziness
|
3.2%
1/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
3.1%
1/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
Nervous system disorders
Headache
|
0.00%
0/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
3.1%
1/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
Nervous system disorders
Paraesthesia
|
3.2%
1/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
2.9%
1/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
Gastrointestinal disorders
Nausea
|
3.2%
1/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
General disorders
Chest pain
|
0.00%
0/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
2.9%
1/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
General disorders
Fatigue
|
0.00%
0/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
3.1%
1/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.2%
1/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
3.0%
1/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
2.9%
1/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
6.2%
2/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
3.0%
1/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
Vascular disorders
Haematoma
|
0.00%
0/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
3.0%
1/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/31 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/32 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
0.00%
0/34 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
3.0%
1/33 • Serious adverse events were recorded from the signing of the informed consent and adverse events were recorded from randomization until the final follow-up visit.
|
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