Trial Outcomes & Findings for A Pharmacodynamic Study With Ticagrelor in African American Patients (NCT NCT01523392)

NCT ID: NCT01523392

Last Updated: 2014-10-08

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 50 participants
• Primary outcome timeframe: At 2 hours after the loading dose
• Results posted on: 2014-10-08

Participant Flow

Patients recruited from 8 participating centers in the United States from 28 March 2012 until 04 September 2013

50 patients screened; 34 patients randomized; 30 patients completed the study (7, 8, or 9 days of both treatments), and 31 completed follow-up

Participant milestones

Measure	Ticagrelor (Period 1) Then Clopidogrel (Period 2) Sequence Ticagrelor 180 milligrams (mg) loading dose followed by 90 mg twice daily (bd) for 7, 8 or 9 days (Period 1), and then clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 7, 8 or 9 days (Period 2)	Clopidogrel (Period 1) Then Ticagrelor (Period 2) Sequence Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days (Period 1), and then ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days (Period 2)
Treatment Period 1 STARTED	20	14
Treatment Period 1 COMPLETED	17	14
Treatment Period 1 NOT COMPLETED	3	0
Washout Period - 10 to 14 Days STARTED	18	14
Washout Period - 10 to 14 Days COMPLETED	17	14
Washout Period - 10 to 14 Days NOT COMPLETED	1	0
Treatment Period 2 STARTED	17	14
Treatment Period 2 COMPLETED	17	14
Treatment Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Ticagrelor (Period 1) Then Clopidogrel (Period 2) Sequence Ticagrelor 180 milligrams (mg) loading dose followed by 90 mg twice daily (bd) for 7, 8 or 9 days (Period 1), and then clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 7, 8 or 9 days (Period 2)	Clopidogrel (Period 1) Then Ticagrelor (Period 2) Sequence Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days (Period 1), and then ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days (Period 2)
Treatment Period 1 Withdrawal by Subject	2	0
Treatment Period 1 Did not complete 7-9 days of treatment.	1	0
Washout Period - 10 to 14 Days Adverse Event	1	0

Baseline Characteristics

A Pharmacodynamic Study With Ticagrelor in African American Patients

Baseline characteristics by cohort

Measure	Ticagrelor (Period 1) Then Clopidogrel (Period 2) Sequence n=20 Participants Ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days (Period 1), and then clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days (Period 2)	Clopidogrel (Period 1) Then Ticagrelor (Period 2) Sequence n=14 Participants Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days (Period 1), and then ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days (Period 2)	Total n=34 Participants Total of all reporting groups
Age, Customized <18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized >=18 to <65 years	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Age, Customized >= 65 years	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Region of Enrollment United States	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 2 hours after the loading dose

Population: Pharmacodynamic (PD) Analysis Set (N=32) - included all participants for whom PD data was available with no major protocol deviations thought to significantly affect the PD of ticagrelor or clopidogrel

Outcome measures

Measure	Ticagrelor n=29 Participants Ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days	Clopidogrel n=28 Participants Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days
Inhibition of the P2Y12 Receptor as Measured by Platelet Reaction Unit (PRU) From VerifyNow™ (a Platelet Function Test Developed by Accumetrics) at 2 Hours After Loading Dose	27.6 PRU Interval 4.9 to 50.2	211.2 PRU Interval 188.3 to 234.0

SECONDARY outcome

Timeframe: At 0.5 hour and 8 hours after the loading dose

Population: PD Analysis Set

Outcome measures

Measure	Ticagrelor n=29 Participants Ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days	Clopidogrel n=28 Participants Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days
Inhibition of the P2Y12 Receptor as Measured by PRU From VerifyNow™ at 0.5 Hour and 8 Hours After Loading Dose 0.5 hours	166.3 PRU Interval 137.9 to 194.8	270.1 PRU Interval 241.3 to 298.8
Inhibition of the P2Y12 Receptor as Measured by PRU From VerifyNow™ at 0.5 Hour and 8 Hours After Loading Dose 8 hours (N=28 ticagrelor, N=27 clopidogrel)	27.2 PRU Interval 4.3 to 50.2	192.6 PRU Interval 169.3 to 215.8

SECONDARY outcome

Timeframe: At 2 hours and 8 hours on Day 7 after multiple doses and at end of dosing interval on Day 8

Population: PD Analysis Set

Outcome measures

Measure	Ticagrelor n=28 Participants Ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days	Clopidogrel n=27 Participants Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days
Inhibition of the P2Y12 Receptor as Measured by PRU From VerifyNow™ at 2 Hours and 8 Hours on Day 7 After Multiple Doses and at End of Dosing Interval on Day 8 2 hours on Day 7 (N=27 for clopidogrel)	22.9 PRU Interval 1.4 to 44.4	157.8 PRU Interval 135.9 to 179.8
Inhibition of the P2Y12 Receptor as Measured by PRU From VerifyNow™ at 2 Hours and 8 Hours on Day 7 After Multiple Doses and at End of Dosing Interval on Day 8 8 hours on Day 7	28.5 PRU Interval 7.7 to 49.2	146.5 PRU Interval 125.6 to 167.4
Inhibition of the P2Y12 Receptor as Measured by PRU From VerifyNow™ at 2 Hours and 8 Hours on Day 7 After Multiple Doses and at End of Dosing Interval on Day 8 End of dosing interval on Day 8	39.3 PRU Interval 17.8 to 60.7	172.7 PRU Interval 151.2 to 194.2

SECONDARY outcome

Timeframe: Predose, 0.5 hour, 2 hours, 8 hours from loading dose; 0, 2 hours, 8 hours and 12 hours from last dose

Population: Pharmacokinetic (PK) Analysis Set - included all patients for whom at least one valid PK reading was available

The standard deviation (SD) is the geometric SD

Outcome measures

Measure	Ticagrelor n=20 Participants Ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days	Clopidogrel n=11 Participants Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days
Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses Baseline (0 pre-dose hours)	1.0 ng/mL Standard Deviation 1.0	1.2 ng/mL Standard Deviation 1.8
Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses 0.5 hours after the loading dose	206.6 ng/mL Standard Deviation 5.2	33.7 ng/mL Standard Deviation 8.2
Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses 2 hours after the loading dose	1167.3 ng/mL Standard Deviation 1.8	756.9 ng/mL Standard Deviation 1.9
Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses 8 hours after the loading dose - Period 1 N=19	395.9 ng/mL Standard Deviation 1.5	141.9 ng/mL Standard Deviation 12.1
Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses 0 hours after multiple doses - Period 1 N=18	168.4 ng/mL Standard Deviation 7.3	187.4 ng/mL Standard Deviation 2.1
Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses 2 hours after multiple doses - Period 1 N=18	324.6 ng/mL Standard Deviation 8.9	608.8 ng/mL Standard Deviation 1.9
Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses 8 hours after multiple doses - Period 1 N=18	179.2 ng/mL Standard Deviation 7.4	311.3 ng/mL Standard Deviation 1.7
Ticagrelor Plasma Concentrations After the Loading and Maintenance Doses End of dosing interval on Day 8 - Period 1 N=18	284.9 ng/mL Standard Deviation 2.2	295.7 ng/mL Standard Deviation 1.9

SECONDARY outcome

Timeframe: Predose, 0.5 hour, 2 hours, 8 hours from loading dose and 0, 2 hours, 8 hours and 12 hours from last dose

Population: Pharmacokinetic (PK) Analysis Set - included all patients for whom at least one valid PK reading was available

The standard deviation (SD) is the geometric SD

Outcome measures

Measure	Ticagrelor n=20 Participants Ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days	Clopidogrel n=11 Participants Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days
AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses Baseline (0 pre-dose hours)	1.0 ng/mL Standard Deviation 1.0	1.0 ng/mL Standard Deviation 1.0
AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses 0.5 hours after the loading dose	9.8 ng/mL Standard Deviation 4.9	2.3 ng/mL Standard Deviation 3.2
AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses 2 hours after the loading dose	222.6 ng/mL Standard Deviation 2.7	150.9 ng/mL Standard Deviation 2.5
AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses 8 hours after the loading dose - Period 1 N=19	119.0 ng/mL Standard Deviation 1.7	54.8 ng/mL Standard Deviation 7.5
AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses 0 hours after multiple doses - Period 1 N=18	93.2 ng/mL Standard Deviation 5.8	74.5 ng/mL Standard Deviation 2.0
AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses 2 hours after multiple doses - Period 1 N=18	136.7 ng/mL Standard Deviation 6.3	172.3 ng/mL Standard Deviation 1.7
AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses 8 hours after multiple doses - Period 1 N=18	89.8 ng/mL Standard Deviation 5.6	112.6 ng/mL Standard Deviation 1.3
AR-C124910XX (an Active Metabolite of Ticagrelor) Plasma Concentrations After the Loading and Maintenance Doses End of dosing interval on Day 8 - Period 1 N=18	140.8 ng/mL Standard Deviation 1.9	110.3 ng/mL Standard Deviation 1.4

Adverse Events

Ticagrelor

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Clopidogrel

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ticagrelor n=34 participants at risk Ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days	Clopidogrel n=31 participants at risk Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days
Cardiac disorders Acute Myocardial Infarction	2.9% 1/34 • Number of events 1 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	0.00% 0/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.

Other adverse events

Measure	Ticagrelor n=34 participants at risk Ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days	Clopidogrel n=31 participants at risk Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days
Gastrointestinal disorders Haemorroidal haemorrhage	2.9% 1/34 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	0.00% 0/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.9% 1/34 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	0.00% 0/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 2/34 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	0.00% 0/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.
General disorders Application site bruise	0.00% 0/34 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	3.2% 1/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.
General disorders Vessel puncture site bruise	0.00% 0/34 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	3.2% 1/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.
Investigations Blood glucose decreased	2.9% 1/34 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	0.00% 0/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.
Injury, poisoning and procedural complications Contusion	2.9% 1/34 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	0.00% 0/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/34 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	3.2% 1/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.
Reproductive system and breast disorders Vaginal haemmorhage	0.00% 0/34 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.	3.2% 1/31 • Adverse events were collected from the time of signature of the informed consent throughout the treatment period including the follow up visit (approximately 11 weeks for each participant). Adverse events were solicited at each scheduled visit and could be reported by the participant at any time during the study. When summarizing Treatment Period 1 and Treatment Period 2 totals, each participant was counted only once for an individual adverse event, regardless of whether it occurred on ticagrelor, clopidogrel or both.

Additional Information

Tomas LG Andersson, MD, PhD

AstraZeneca

Phone: 1-800-236-9933

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee An Investigator agrees to provide a copy of the publication to AstraZeneca (AZ) for review at least 60 days in advance of the submission for publication. The Investigators in the Multi-Center (MC) study agree to postpone MC publications until the earlier of the first AstraZeneca-authorized publication or up to eighteen months from study completion at all sites.
• Publication restrictions are in place

Restriction type: OTHER