A Study to Investigate the Effect of Oral Ticagrelor on the Pharmacokinetics of Oral Rosuvastatin When Given in Healthy Participants

An Open-label, Randomised, Parallel-group, Fixed-sequence Study to Assess the Effect of Oral Ticagrelor on the Pharmacokinetics of Oral Rosuvastatin in Healthy Participants

The purpose of this study is to measure the effect of ticagrelor on the pharmacokinetics (PK) of rosuvastatin in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Ticagrelor

Detailed Description

This study will be conducted at a single Clinical Unit. It includes 2 parallel arms (one for each rosuvastatin dose) and 2 treatment periods.

The study will comprise:

• A Screening Period of maximum 28 days.
• Period 1: It will start on Day -1. A single dose of rosuvastatin (dose 1 or dose 2) will be administered on Day 1 followed by PK sampling of rosuvastatin for 96 hours. Participants will be admitted to the Clinical Unit on Study Day -1. Period 1 will end on Study Day 5.
• Period 2: It will start on Study Day 6. A second single dose of rosuvastatin (dose 1 or dose 2) will be administered on Day 6 followed by PK sampling of rosuvastatin for 120 hours. Ticagrelor 90 mg, twice a day will be started on Day 6 (administered concomitantly with rosuvastatin) and administered through Day 10. Period 2 will end on Study Day 12.
• A Follow-up Visit, 4 to 7 days after discharge.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy participants with suitable veins for cannulation or repeated venipuncture.
• All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
• Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception, to avoid pregnancy from the time of first administration of study intervention until 1 month after the study Follow-up Visit.

• Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria:

  1. Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range.
  2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation or tubal occlusion.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the specified contraception methods from the time of first administration of study intervention administration until 2 weeks after the study Follow-up Visit.
• Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

Exclusion Criteria:

• History of any clinically important disease or disorder which may either put the participant at risk or influence the results or the participant's ability to participate in the study.
• History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
• Any clinically important abnormal laboratory values or vital signs.
• Any positive result on Screening for serum HBsAg OR anti-HBc antibody, indicative of active hepatitis B (i.e., participants with positive anti HBc antibody result are acceptable if anti HBc IgM antibodies are negative).
• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months prior to screening.
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol. Excessive intake of alcohol defined as the regular consumption of more than 24 g of alcohol per day for men or 12 g of alcohol per day for females.
• Positive screen for drugs of abuse, or alcohol or cotinine at screening or on admission to the Clinical Unit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin (Dose 1) + Ticagrelor; Participants will receive rosuvastatin (dose 1) orally as a single dose on Day 1 in Period 1 and Day 6 in Period 2. During Period 2, participants will also receive ticagrelor 90 mg BID (twice a day) on Day 6 through Day 10.	Drug: Rosuvastatin; Participants will receive rosuvastatin (dose 1 or dose 2) orally as a single dose on Day 1 in Period 1 and Day 6 in Period 2.; Other Names: CRESTOR; Drug: Ticagrelor; Participants in each arm will receive ticagrelor 90 mg orally BID from Day 6 to Day 10.; Other Names: BRILIQUE
Experimental: Rosuvastatin (Dose 2) + Ticagrelor; Participants will receive rosuvastatin (dose 2) orally as a single dose on Day 1 in Period 1 and Day 6 in Period 2. During Period 2, participants will also receive ticagrelor 90 mg BID on Day 6 through Day 10.	Drug: Rosuvastatin; Participants will receive rosuvastatin (dose 1 or dose 2) orally as a single dose on Day 1 in Period 1 and Day 6 in Period 2.; Other Names: CRESTOR; Drug: Ticagrelor; Participants in each arm will receive ticagrelor 90 mg orally BID from Day 6 to Day 10.; Other Names: BRILIQUE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under concentration-time curve from time 0 to infinity (AUCinf)	To assess the effect of ticagrelor on plasma PK (AUCinf) of rosuvastatin dose 1 and dose 2 separately, in healthy participants.	From Day 1 to Day 11
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)	To assess the effect of ticagrelor on plasma PK (AUClast) of rosuvastatin dose 1 and dose 2 separately, in healthy participants.	From Day 1 to Day 11
Maximum observed drug concentration (Cmax)	To assess the effect of ticagrelor on plasma PK (Cmax) of rosuvastatin dose 1 and dose 2 separately, in healthy participants.	From Day 1 to Day 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	To examine the safety and tolerability of rosuvastatin alone and in combination with ticagrelor.	Approximately 7 weeks
Terminal elimination half-life (t1/2)	To assess the effect of ticagrelor on the PK (t1/2) of rosuvastatin in healthy participants.	From Day 1 to Day 11
Terminal rate constant (parent only) (λz)	To assess the effect of ticagrelor on the PK (λz) of rosuvastatin in healthy participants.	From Day 1 to Day 11
Time to reach maximum observed concentration (tmax)	To assess the effect of ticagrelor on the PK (tmax) of rosuvastatin in healthy participants.	From Day 1 to Day 11
Amount of drug excreted (Ae)	To assess the effect of ticagrelor on the urine PK (Ae) of rosuvastatin in healthy participants.	From Day 1 to Day 11
Renal clearance (Clrenal)	To assess the effect of ticagrelor on the urine PK (Clrenal) of rosuvastatin in healthy participants.	From Day 1 to Day 11
Percent of dose excreted	To assess the effect of ticagrelor on the urine PK of rosuvastatin in healthy participants.	From Day 1 to Day 11

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2024
• Primary Completion (Actual): October 8, 2024
• Study Completion (Actual): October 8, 2024

Study Registration Dates

• First Submitted: August 2, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Ticagrelor; Pharmacokinetics; Rosuvastatin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Neurotransmitter Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ticagrelor; Rosuvastatin Calcium
• Other Study ID Numbers: D3560C00817

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No