Trial Outcomes & Findings for Pharmacokinetics, Pharmacodynamics, and Safety Study of Ticagrelor in Hemodialysis Patients and Healthy Subjects (NCT NCT02022748)
NCT ID: NCT02022748
Last Updated: 2018-01-17
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
27 participants
Primary outcome timeframe
0, 1, 2, 4, 6, 12, 24, 36, 48 hours post-dose
Results posted on
2018-01-17
Participant Flow
56 subjects signed ICF, 34 Hemodialysis (HD) subjects and 22 Healthy subjects (HS) at 2 study centers in the US. 27 subjects received treatment (14 HD and 13 HS). First patient signed ICF on 29 December 2013. Due to protocol amendment, the first patient was randomized 22 months later on 20 October 2015, last patient last visit was 09 May 2016.
21 out of 34 HD subjects were randomized (13 failed to fulfill eligibility criteria) and 14 were eligible after eligibility re-assessment (5 no longer met the eligibility criteria and 2 experienced Adverse Events (AE) prior to treatment). 13 out of 22 HS were eligible to be treated (9 failed to meet the eligibility criteria).
Participant milestones
| Measure |
Sequence 1 (AB)
hemodialysis patients: subjects will receive treatment A (ticagrelor oral 90 mg 1 day following the dialysis session but 2 days before the next dialysis session) in period 1 and treatment B (ticagrelor oral 90 mg just prior to dialysis session) in period 2.
|
Sequence 2 (BA)
Hemodialysis patients: subjects will receive treatment B (ticagrelor oral 90 mg just prior to dialysis session) in period 1 and treatment A (ticagrelor oral 90 mg 1 day following the dialysis session but 2 days before the next dialysis session) in period 2.
|
Treatment H
Healthy subjects: ticagrelor oral 90 mg on 1 day of treatment
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
6
|
13
|
|
Overall Study
Subject Who Started Treatment
|
8
|
6
|
13
|
|
Overall Study
Subjects Who Completed Treatment
|
7
|
4
|
13
|
|
Overall Study
COMPLETED
|
7
|
4
|
13
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1 (AB)
hemodialysis patients: subjects will receive treatment A (ticagrelor oral 90 mg 1 day following the dialysis session but 2 days before the next dialysis session) in period 1 and treatment B (ticagrelor oral 90 mg just prior to dialysis session) in period 2.
|
Sequence 2 (BA)
Hemodialysis patients: subjects will receive treatment B (ticagrelor oral 90 mg just prior to dialysis session) in period 1 and treatment A (ticagrelor oral 90 mg 1 day following the dialysis session but 2 days before the next dialysis session) in period 2.
|
Treatment H
Healthy subjects: ticagrelor oral 90 mg on 1 day of treatment
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
Baseline Characteristics
Pharmacokinetics, Pharmacodynamics, and Safety Study of Ticagrelor in Hemodialysis Patients and Healthy Subjects
Baseline characteristics by cohort
| Measure |
HD Subjects
n=14 Participants
Hemodialysis subjects
|
HS Subjects
n=13 Participants
Healthy subjects
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.6 years
STANDARD_DEVIATION 12.5 • n=5 Participants
|
43.8 years
STANDARD_DEVIATION 10.4 • n=7 Participants
|
47.3 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Weight
|
85.1 kg
STANDARD_DEVIATION 18.3 • n=5 Participants
|
89.0 kg
STANDARD_DEVIATION 16.2 • n=7 Participants
|
87.0 kg
STANDARD_DEVIATION 17.1 • n=5 Participants
|
|
BMI
|
27.77 kg/m^2
STANDARD_DEVIATION 4.18 • n=5 Participants
|
28.27 kg/m^2
STANDARD_DEVIATION 3.75 • n=7 Participants
|
28.01 kg/m^2
STANDARD_DEVIATION 3.91 • n=5 Participants
|
PRIMARY outcome
Timeframe: 0, 1, 2, 4, 6, 12, 24, 36, 48 hours post-dosePopulation: The Pharmacokinetic (PK) analysis set included all subjects who received at least 1 dose of study medication and for whom PK data are available with no major protocol deviations thought to significantly affect the pharmacokinetics of ticagrelor or its active metabolite AR-C124910XX.
Outcome measures
| Measure |
Treatment A
n=12 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session;
|
Treatment B
n=13 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet just prior to dialysis session.
|
Treatment H
n=13 Participants
Healthy subjects (HS) with normal renal function (CrCL of ≥90 mL/min) received one oral 90 mg ticagrelor tablet
|
|---|---|---|---|
|
Pharmacokinetic Parameter Cmax of Ticagrelor
|
560.32 ng/mL
Geometric Coefficient of Variation 54.0
|
598.35 ng/mL
Geometric Coefficient of Variation 47.9
|
370.76 ng/mL
Geometric Coefficient of Variation 37.3
|
PRIMARY outcome
Timeframe: 0, 1, 2, 4, 6, 12, 24, 36, 48 hours post-dosePopulation: The PK analysis set included all subjects who received at least 1 dose of study medication and for whom PK data are available with no major protocol deviations thought to significantly affect the pharmacokinetics of ticagrelor or its active metabolite AR-C124910XX.
Outcome measures
| Measure |
Treatment A
n=12 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session;
|
Treatment B
n=13 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet just prior to dialysis session.
|
Treatment H
n=13 Participants
Healthy subjects (HS) with normal renal function (CrCL of ≥90 mL/min) received one oral 90 mg ticagrelor tablet
|
|---|---|---|---|
|
Pharmacokinetic Parameter Cmax of AR-C124910XX
|
130.82 ng/mL
Geometric Coefficient of Variation 38.3
|
152.25 ng/mL
Geometric Coefficient of Variation 54.3
|
111.73 ng/mL
Geometric Coefficient of Variation 60.0
|
PRIMARY outcome
Timeframe: 0, 1, 2, 4, 6, 12, 24, 36, 48 hours post-dosePopulation: The PK analysis set included all subjects who received at least 1 dose of study medication and for whom PK data are available with no major protocol deviations thought to significantly affect the pharmacokinetics of ticagrelor or its active metabolite AR-C124910XX.
Outcome measures
| Measure |
Treatment A
n=12 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session;
|
Treatment B
n=13 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet just prior to dialysis session.
|
Treatment H
n=13 Participants
Healthy subjects (HS) with normal renal function (CrCL of ≥90 mL/min) received one oral 90 mg ticagrelor tablet
|
|---|---|---|---|
|
Pharmacokinetic Parameter AUC0-∞ (Area Under the Plasma Concentration-time Curve From Time Zero to Infinity) of Ticagrelor
|
3015.1 ng*h/mL
Geometric Coefficient of Variation 54.2
|
3256.1 ng*h/mL
Geometric Coefficient of Variation 52.5
|
2188.8 ng*h/mL
Geometric Coefficient of Variation 22.6
|
PRIMARY outcome
Timeframe: 0, 1, 2, 4, 6, 12, 24, 36, 48 hours post-dosePopulation: The PK analysis set included all subjects who received at least 1 dose of study medication and for whom PK data are available with no major protocol deviations thought to significantly affect the pharmacokinetics of ticagrelor or its active metabolite AR-C124910XX.
Outcome measures
| Measure |
Treatment A
n=12 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session;
|
Treatment B
n=13 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet just prior to dialysis session.
|
Treatment H
n=13 Participants
Healthy subjects (HS) with normal renal function (CrCL of ≥90 mL/min) received one oral 90 mg ticagrelor tablet
|
|---|---|---|---|
|
Pharmacokinetic Parameter AUC0-∞ of AR-C124910XX
|
1127.8 ng*h/mL
Geometric Coefficient of Variation 39.3
|
1144.2 ng*h/mL
Geometric Coefficient of Variation 36.2
|
1000.4 ng*h/mL
Geometric Coefficient of Variation 33.2
|
SECONDARY outcome
Timeframe: 3 daysPopulation: The PK analysis set included all subjects who received at least 1 dose of study medication and for whom PK data are available with no major protocol deviations thought to significantly affect the pharmacokinetics of ticagrelor or its active metabolite AR-C124910XX.
Outcome measures
| Measure |
Treatment A
n=12 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session;
|
Treatment B
n=13 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet just prior to dialysis session.
|
Treatment H
n=13 Participants
Healthy subjects (HS) with normal renal function (CrCL of ≥90 mL/min) received one oral 90 mg ticagrelor tablet
|
|---|---|---|---|
|
Pharmacokinetic Parameter t1/2 of Ticagrelor
|
8.303 hour
Standard Deviation 1.250
|
8.691 hour
Standard Deviation 2.298
|
8.412 hour
Standard Deviation 1.248
|
SECONDARY outcome
Timeframe: 3 daysPopulation: The PK analysis set included all subjects who received at least 1 dose of study medication and for whom PK data are available with no major protocol deviations thought to significantly affect the pharmacokinetics of ticagrelor or its active metabolite AR-C124910XX.
Outcome measures
| Measure |
Treatment A
n=12 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session;
|
Treatment B
n=13 Participants
HD subjects were dosed with an oral 90 mg ticagrelor tablet just prior to dialysis session.
|
Treatment H
n=13 Participants
Healthy subjects (HS) with normal renal function (CrCL of ≥90 mL/min) received one oral 90 mg ticagrelor tablet
|
|---|---|---|---|
|
Pharmacokinetic Parameter t1/2 of AR-C124910XX
|
7.574 hour
Standard Deviation 2.079
|
7.596 hour
Standard Deviation 1.757
|
8.644 hour
Standard Deviation 2.414
|
Adverse Events
Treatment A
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Treatment B
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Treatment H
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment A
n=12 participants at risk
HD subjects were dosed with an oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session;
|
Treatment B
n=13 participants at risk
HD subjects were dosed with an oral 90 mg ticagrelor tablet just prior to dialysis session.
|
Treatment H
n=13 participants at risk
Healthy subjects (HS) with normal renal function (CrCL of ≥90 mL/min) received one oral 90 mg ticagrelor tablet
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.00%
0/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Number of events 1 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
Other adverse events
| Measure |
Treatment A
n=12 participants at risk
HD subjects were dosed with an oral 90 mg ticagrelor tablet 1 day following the dialysis session but 2 days before the next dialysis session;
|
Treatment B
n=13 participants at risk
HD subjects were dosed with an oral 90 mg ticagrelor tablet just prior to dialysis session.
|
Treatment H
n=13 participants at risk
Healthy subjects (HS) with normal renal function (CrCL of ≥90 mL/min) received one oral 90 mg ticagrelor tablet
|
|---|---|---|---|
|
Metabolism and nutrition disorders
Fluid overload
|
8.3%
1/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Nervous system disorders
Headache
|
0.00%
0/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Nervous system disorders
Migraine
|
0.00%
0/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Nervous system disorders
Restless legs syndrome
|
0.00%
0/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
8.3%
1/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.00%
0/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
General disorders
Tenderness
|
0.00%
0/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/12 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
0.00%
0/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
7.7%
1/13 • Starting from the date of first dose of study medication to follow-up (5-10 days post discharge unit). For HD Subjects, events that occurred during the washout or follow-up periods are attributed to the previous treatment taken.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PIs shall be entitled to publish or make presentations related to the Study within 2 years of completion of the Study with Sponsor's prior written consent. PIs shall provide the Sponsor with copies of any materials at least thirty (30) days in advance of publication, submission or presentation. All such publications or presentations shall be consistent with applicable standards, guidelines and laws, not be false or misleading, and not be made for any commercial purpose.
- Publication restrictions are in place
Restriction type: OTHER