Cardiovascular DiseasePhase 1NCT04588727
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AZD3366 in Healthy Subjects, Japanese and Chinese Subjects
A Phase 1 study testing AZD3366, Ticagrelor and acetylsalicylic acid (ASA) in people with Cardiovascular Disease, run by AstraZeneca at 1 site in United States.
Trial summary
Part A of this study is a Phase 1, First-in-human (FiH), randomized, single-blind, placebo controlled study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD3366 following single intravenous (IV) ascending doses. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Disease
- What is being tested?
- AZD3366, Ticagrelor and acetylsalicylic acid (ASA)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2020to 19 Jan 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men and women of non-childbearing potential
- Females must have a negative pregnancy test at Screening and on admission to the study center, must not be lactating, and must be of non-childbearing potential, confirmed at Screening, by fulfilling one of the below criteria:
- Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and Follicle stimulating hormone levels in the postmenopausal range.
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not bilateral tubal ligation.
- Subjects described as healthy subjects are defined as not having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent [for example, Cambodia, China, India, Indonesia, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam] except for subjects enrolled into the Japanese (subject for whom both parents and all grandparents are Japanese; born in Japan and not lived outside Japan for more than 10 years) and Chinese (a subject for whom both parents and all grandparents are Chinese and not lived outside of China for more than 10 years) cohorts.
- Body mass index: 18 and 30 kg/m^2, and weigh minimum 50 kg and not >100 kg.
Who cannot join
- Subjects having history of the following are excluded:
- Any clinically important disease or disorder which, may put the subject at risk, or influence the results or the subject's ability to participate in the study.
- History or presence of gastrointestinal, hepatic or renal disease or other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
- Hemophilia, von Willebrand´s disease, lupus anticoagulant or other diseases/syndromes that can either alter or increase the propensity of bleeding.
- Any clinically significant non-traumatic bleed or clinically significant enhanced bleeding.
- Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
Show all 34Show fewer
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD3366 or to ASA or ticagrelor.
- Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results, coagulation parameters, including but not limited to the list below:
- Alanine aminotransferase > upper limit of normal (ULN)
- Aspartate aminotransferase > ULN
- Creatinine > ULN
- White blood cell count < lower limit of normal (LLN)
- Hemoglobin < LLN
- Platelet count < 150,000/µL
- Total bilirubin 1.2 x > ULN
- Subjects with positive serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus.
- Any abnormal vital signs, after 10 minutes supine rest, as defined in the list below, at the Screening Visit and/or Day -1:
- Systolic blood pressure (BP) < 90 mmHg or > 140 mmHg.
- Diastolic BP < 50 mmHg or > 90 mmHg.
- Heart rate <45 or >85 beats per minute.
- Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG, which may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology.
- Current smokers or those who have smoked or used nicotine products within the previous 3 months, or history of alcohol abuse or excessive intake of alcohol.
- Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega-dose vitamins and minerals during the 2 weeks prior to the first administration of IMP or 5 x the half-life of the drug (whichever is longer).
- Plasma donation within one month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
- COVID-19 vaccination has been administered and a period of less than 14 days has elapsed after the second dose of the vaccine prior to randomization.
- Received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days (or 5 half-lives, whichever is longer) of the first administration of IMP in this study.
- Scheduled surgery, including dental surgery, within 8 weeks of the scheduled completion date of the study.
- Anti-platelet therapy, anticoagulation therapy (i.e., warfarin, factor Xa inhibitors, direct thrombin inhibitors, or heparin), or thrombolytic use, in the past month prior to randomization or planned use during the duration of the study.
- Use of non-steroidal anti-inflammatory drugs (including ibuprofen) within 3 days prior to the randomization.
- Use of potent cytochrome 3A4/3A5 and/or P-glycoprotein inhibiting or inducing drugs during the 2 weeks prior to the first administration of IMP or 5 x the half-life of the drug (whichever is longer).
- Subjects who are vegans.
- Subjects who cannot communicate reliably with the investigator.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD3366 in Healthy Men and Women of Non-Childbearing Potential Following: Part A: Single Ascending Dose Administration (Including Populations of Japanese and Chinese Subjects) Part B: Single Dose Administration of AZD3366 at One Dose Level or Placebo With Concomitant Repeated Dosing of Ticagrelor and Acetylsalicylic Acid
Part A of this study is a Phase 1, First-in-human (FiH), randomized, single-blind, placebo controlled study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD3366 following single intravenous (IV) ascending doses.
Part B of this study is a randomized, single-blind, parallel group placebo-controlled study to assess the safety, tolerability and PD of a single IV administration of AZD3366 with concomitant loading doses followed by repeated maintenance dosing of ticagrelor and acetylsalicylic acid (ASA).
Read the detailed description
The study will provide data on safety, tolerability, PK, and PD of AZD3366 in healthy subjects. Three populations (healthy subjects, healthy Japanese subjects and healthy Chinese subjects) will be enrolled into this study.
This study will be conducted at a single study center in United States of America (USA).
Part A of the study will investigate the safety, tolerability, PK, and PD (inhibition of platelet aggregation and capillary bleeding time [CBT]) of an IV administration of single ascending doses (SAD) of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects.
Part B of the study will investigate the safety, tolerability, and PD (inhibition of platelet aggregation and CBT) of a single IV dose of AZD3366 or placebo with concomitant administration of ticagrelor and ASA by a parallel group cohort consisting of of healthy subjects. Furthermore, the potential effect of AZD3366 on the PK of ticagrelor will be investigated. Co-medication with ASA and ticagrelor is chosen based on the Standard of Care anti-platelet treatment regimen in patients with myocardial infarction.
- Conditions
- Cardiovascular Disease
- Being tested
- AZD3366, Placebo, Ticagrelor, acetylsalicylic acid (ASA)
- Keywords
- Pharmacokinetics, Cardiovascular disease, Acute myocardial infarction, Acute ischemic stroke, First in Human, Healthy subjects, Healthy Japanese subjects, Healthy Chinese subjects
- Medical subject headings
- Cardiovascular Diseases, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD3366Drug
In Part A, subjects will be randomized to receive intravenous infusion AZD3366 dose 1-7, single ascending dose (SAD). In Part A, Dose 2-7 may be adjusted based on PK data from previous cohort[s]. In Part B, subjects will be randomized to receive intravenous infusion AZD3366 dose X (a dose resulting in predicted therapeutic exposure).
PlaceboDrug
In Part A and Part B, subjects will be randomized to receive intravenous infusion of placebo (0.9% sodium chloride solution).
TicagrelorDrug
Also called Brilinta
In Part B, subjects will receive oral ticagrelor tablets.
acetylsalicylic acid (ASA)Drug
Also called Chewable aspirin
In Part B, subjects will receive oral ASA chewable tablets.
| Study group | Role | What they receive |
|---|---|---|
| AZD3366 Dose 1 Part A | Experimental | Randomized healthy subjects will receive Dose 1 of AZD3366. Receives: Drug: AZD3366 |
| AZD3366 Dose 2 Part A | Experimental | Randomized healthy subjects will receive Dose 2 of AZD3366. Receives: Drug: AZD3366 |
| AZD3366 Dose 3 Part A | Experimental | Randomized healthy subjects will receive Dose 3 of AZD3366. Receives: Drug: AZD3366 |
| AZD3366 Dose 4 Part A | Experimental | Randomized healthy subjects will receive Dose 4 of AZD3366. Receives: Drug: AZD3366 |
| AZD3366 Dose 5 Part A | Experimental | Randomized healthy subjects and healthy Japanese subjects will receive Dose 5 of AZD3366. Receives: Drug: AZD3366 |
| AZD3366 Dose 6 Part A | Experimental | Randomized healthy subjects and healthy Japanese subjects will receive Dose 6 of AZD3366. Receives: Drug: AZD3366 |
| AZD3366 Dose 7 Part A | Experimental | Randomized healthy subjects, healthy Japanese subjects, and healthy Chinese subjects will receive Dose 7 of AZD3366. Receives: Drug: AZD3366 |
| Placebo Part A | Placebo comparator | Randomized healthy subjects, healthy Japanese subjects, and healthy Chinese subjects will receive Placebo matched to AZD3366. Receives: Drug: Placebo |
| AZD3366 Dose X Part B | Experimental | Randomized healthy subjects will receive Dose X of AZD3366 in conjunction with concomitant administration of ticagrelor and ASA. Receives: Drug: AZD3366; Drug: Ticagrelor; Drug: acetylsalicylic acid (ASA) |
| Placebo Dose X Part B | Placebo comparator | Randomized healthy subjects will receive Dose X of placebo in conjunction with concomitant administration of ticagrelor and ASA. Receives: Drug: Placebo; Drug: Ticagrelor; Drug: acetylsalicylic acid (ASA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with adverse events and serious adverse events in both Part A and Part B
Adverse events will be assessed to investigate the safety and tolerability of intravenous administration of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects.
Measured: From screening (Day -21) to follow-up (Day 60 for Part A and Day 50 for Part B)
Secondary outcomes (26)
Area under plasma concentration-time curve from time zero extrapolated to infinity (AUCinf) to characterize the PK of AZD3366 in Part A
To characterize the PK of AZD3366 following IV administration of single doses of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose, and post-dose (Day 1 to Day 60)
Terminal half life (t½λz), estimated as (ln2)/λz to characterize the PK of AZD3366 in Part A
To characterize the PK of AZD3366 following IV administration of single doses of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose, and post-dose (Day 1 to Day 60)
Total body clearance of drug from plasma after intravascular administration (CL) to characterize the PK of AZD3366 in Part A
To characterize the PK of AZD3366 following IV administration of single doses of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose, and post-dose (Day 1 to Day 60)
Volume of distribution at steady state from a systemic dose (Vss) to characterize the PK of AZD3366 in Part A
To characterize the PK of AZD3366 following IV administration of single doses of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose, and post-dose (Day 1 to Day 60)
Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast) to characterize the PK of AZD3366 in Part A
To characterize the PK of AZD3366 following IV administration of single doses of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose, and post-dose (Day 1 to Day 60)
Area under the plasma concentration-time curve from time zero to 48 hours after dosing [AUC(0-48)] to characterize the PK of AZD3366 in Part A
To characterize the PK of AZD3366 following IV administration of single doses of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose, and post-dose (Day 1 to Day 60)
Observed maximum plasma concentration (Cmax) to characterize the PK of AZD3366 in Part A
To characterize the PK of AZD3366 following IV administration of single doses of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose, and post-dose (Day 1 to Day 60)
Time to reach peak or maximum observed concentration following drug administration (tmax) to characterize the PK of AZD3366 in Part A
To characterize the PK of AZD3366 following IV administration of single doses of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose, and post-dose (Day 1 to Day 60)
To study the platelet aggregration of AZD3366 in Part A
To study platelet aggregation by Light Transmision Aggregometry (LTA) in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose, and post-dose (Day 1 to Day 60)
Assessment of the duration of capillary bleeding time (CBT) to characterize the PD of AZD3366 in Part A
To characterize the PD of AZD3366 following IV administration of single doses of AZD3366 with respect to inhibition of CBT in healthy subjects, healthy Japanese subjects and healthy Chinese subjects in Part A.
Measured: Pre-dose and post-dose (Day 1)
Collection of blood samples for the analyses of antidrug antibodies (ADAs) in both Part A and Part B
To explore immunogenicity following IV administration of AZD3366 in both Part A and Part B.
Measured: At Day -1, Day 15, Day 23 and Day 44 in Part A, and pre-dose (Day 1), Day 15, Day 29 and Day 50 in Part B
Collection of blood samples for adenosine diphosphate-induced associated periodic-induced platelet aggregation in platelet-rich plasma to characterize the PD of AZD3366 in Part B
To study the plasma exposure and characterize the PD of AZD3366 with respect to inhibition of platelet aggregation LTA, following IV administration of AZD3366 at one dose level in healthy subjects with concomitant loading dose and repeated dosing of ticagrelor and ASA in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
Collection of blood samples for tumor necrosis factor receptor associated periodic-induced platelet aggregation in platelet-rich plasma to characterize the PD of AZD3366 in Part B
To study the plasma exposure and characterize the PD of AZD3366 with respect to inhibition of platelet aggregation LTA, following IV administration of AZD3366 at one dose level in healthy subjects with concomitant loading dose and repeated dosing of ticagrelor and ASA in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
CBT to characterize the PD of AZD3366 in Part B
To study the PD (inhibition of CBT) of AZD3366 at 1 dose level in healthy subjects with concomitant loading dose and repeated dosing of ticagrelor and ASA in Part B.
Measured: Pre- dose and post-dose (Day 1 and Day 3)
AUClast to characterize the plasma exposure and PD of AZD3366 in Part B
To study the plasma exposure, and PD (inhibition of platelet aggregation and CBT) of AZD3366 at 1 dose level in healthy subjects with concomitant loading dose and repeated dosing of ticagrelor and ASA in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
AUC(0-48) to characterize the plasma exposure and PD of AZD3366 in Part B
To study the plasma exposure, and PD (inhibition of platelet aggregation and CBT) of AZD3366 at 1 dose level in healthy subjects with concomitant loading dose and repeated dosing of ticagrelor and ASA in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
Cmax to characterize the plasma exposure and PD of AZD3366 in Part B
To study the plasma exposure, and PD (inhibition of platelet aggregation and CBT) of AZD3366 at 1 dose level in healthy subjects with concomitant loading dose and repeated dosing of ticagrelor and ASA in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
tmax to characterize the plasma exposure and PD of AZD3366 in Part B
To study the plasma exposure, and PD (inhibition of platelet aggregation and CBT) of AZD3366 at 1 dose level in healthy subjects with concomitant loading dose and repeated dosing of ticagrelor and ASA in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
AUCinf to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
To study the effect of AZD3366 on the PK of ticagrelor in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3)
AUClast to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
To study the effect of AZD3366 on the PK of ticagrelor in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3)
tmax to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
To study the effect of AZD3366 on the PK of ticagrelor in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3)
t½λz to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
To study the effect of AZD3366 on the PK of ticagrelor in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3)
Area under the plasma concentration-time curve from time zero to 12 hours after dosing [AUC(0-12)] to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
To study the effect of AZD3366 on the PK of ticagrelor in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3)
Cmax to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
To study the effect of AZD3366 on the PK of ticagrelor in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3)
Observed trough plasma concentration after the first dose (Ctrough) to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
To study the effect of AZD3366 on the PK of ticagrelor in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3)
Arithmetic mean of plasma concentration (C) at 12, 24, 36 and 48 hrs post-dose [Cmean (12, 24, 36, 48 hrs)] to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
To study the effect of AZD3366 on the PK of ticagrelor in Part B.
Measured: Pre-dose and post-dose (Day 1 to Day 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start15 Oct 2020
- Primary completion19 Jan 2022
- Study completion19 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Han, Principal investigator, PAREXEL Early Phase Clinical Unit Los Angeles 1560 Chevy Chase Drive, Suite 140 Glendale, CA 91206 United States of America
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04588727
- Sponsor's protocol ID
- D2911C00001
- Status last verified
- Dec 2023
- First submitted
- 9 Oct 2020
- Last updated
- 18 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. 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 shared.
Publications
Kardassis D, Egnell AC, Astrand M, Daniels SJ, Whatling C, Fjellstrom O, Gabrielsen A. Safety, Tolerability, and Pharmacodynamics of AZD3366 (Optimized Human CD39L3 Apyrase) Alone and in Combination With Ticagrelor and Acetylsalicylic Acid: A Phase 1, Randomized, Placebo-Controlled Study. J Am Heart Assoc. 2024 Jun 4;13(11):e033985. doi: 10.1161/JAHA.123.033985. Epub 2024 May 28.
PubMed 38804212
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD3366 in Healthy Men and Women of Non-Childbearing Potential Following: Part A: Single Ascending Dose Administration (Including Populations of Japanese and Chinese Subjects) Part B: Single Dose Administration of AZD3366 at One Dose Level or Placebo With Concomitant Repeated Dosing of Ticagrelor and Acetylsalicylic Acid
- ClinicalTrials.gov ID
- NCT04588727
- Acronym / sponsor ID
- D2911C00001
- Conditions
- Cardiovascular Disease
- Keywords
- Pharmacokinetics, Cardiovascular disease, Acute myocardial infarction, Acute ischemic stroke, First in Human, Healthy subjects, Healthy Japanese subjects, Healthy Chinese subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 15 Oct 2020 (actual)
- Primary completion
- 19 Jan 2022 (actual)
- Study completion
- 19 Jan 2022 (actual)
- First posted
- 19 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Part A of this study is a Phase 1, First-in-human (FiH), randomized, single-blind, placebo controlled study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD3366 following single intravenous (IV) ascending doses.
Part B of this study is a randomized, single-blind, parallel group placebo-controlled study to assess the safety, tolerability and PD of a single IV administration of AZD3366 with concomitant loading doses followed by repeated maintenance dosing of ticagrelor and acetylsalicylic acid (ASA).
Detailed description
The study will provide data on safety, tolerability, PK, and PD of AZD3366 in healthy subjects. Three populations (healthy subjects, healthy Japanese subjects and healthy Chinese subjects) will be enrolled into this study.
This study will be conducted at a single study center in United States of America (USA).
Part A of the study will investigate the safety, tolerability, PK, and PD (inhibition of platelet aggregation and capillary bleeding time [CBT]) of an IV administration of single ascending doses (SAD) of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects.
Part B of the study will investigate the safety, tolerability, and PD (inhibition of platelet aggregation and CBT) of a single IV dose of AZD3366 or placebo with concomitant administration of ticagrelor and ASA by a parallel group cohort consisting of of healthy subjects. Furthermore, the potential effect of AZD3366 on the PK of ticagrelor will be investigated. Co-medication with ASA and ticagrelor is chosen based on the Standard of Care anti-platelet treatment regimen in patients with myocardial infarction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| AZD3366 Dose 1 Part A | Experimental | Drug: AZD3366Randomized healthy subjects will receive Dose 1 of AZD3366. |
| AZD3366 Dose 2 Part A | Experimental | Drug: AZD3366Randomized healthy subjects will receive Dose 2 of AZD3366. |
| AZD3366 Dose 3 Part A | Experimental | Drug: AZD3366Randomized healthy subjects will receive Dose 3 of AZD3366. |
| AZD3366 Dose 4 Part A | Experimental | Drug: AZD3366Randomized healthy subjects will receive Dose 4 of AZD3366. |
| AZD3366 Dose 5 Part A | Experimental | Drug: AZD3366Randomized healthy subjects and healthy Japanese subjects will receive Dose 5 of AZD3366. |
| AZD3366 Dose 6 Part A | Experimental | Drug: AZD3366Randomized healthy subjects and healthy Japanese subjects will receive Dose 6 of AZD3366. |
| AZD3366 Dose 7 Part A | Experimental | Drug: AZD3366Randomized healthy subjects, healthy Japanese subjects, and healthy Chinese subjects will receive Dose 7 of AZD3366. |
| Placebo Part A | Placebo comparator | Drug: PlaceboRandomized healthy subjects, healthy Japanese subjects, and healthy Chinese subjects will receive Placebo matched to AZD3366. |
| AZD3366 Dose X Part B | Experimental | Drug: AZD3366, Drug: Ticagrelor, Drug: acetylsalicylic acid (ASA)Randomized healthy subjects will receive Dose X of AZD3366 in conjunction with concomitant administration of ticagrelor and ASA. |
| Placebo Dose X Part B | Placebo comparator | Drug: Placebo, Drug: Ticagrelor, Drug: acetylsalicylic acid (ASA)Randomized healthy subjects will receive Dose X of placebo in conjunction with concomitant administration of ticagrelor and ASA. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Healthy men and women of non-childbearing potential
- Females must have a negative pregnancy test at Screening and on admission to the study center, must not be lactating, and must be of non-childbearing potential, confirmed at Screening, by fulfilling one of the below criteria:
- Subjects described as healthy subjects are defined as not having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent [for example, Cambodia, China, India, Indonesia, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam] except for subjects enrolled into the Japanese (subject for whom both parents and all grandparents are Japanese; born in Japan and not lived outside Japan for more than 10 years) and Chinese (a subject for whom both parents and all grandparents are Chinese and not lived outside of China for more than 10 years) cohorts.
- Body mass index: 18 and 30 kg/m^2, and weigh minimum 50 kg and not >100 kg.
Key exclusion criteria (34 listed)
- Subjects having history of the following are excluded:
- Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results, coagulation parameters, including but not limited to the list below:
- Subjects with positive serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus.
- Any abnormal vital signs, after 10 minutes supine rest, as defined in the list below, at the Screening Visit and/or Day -1:
- Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG, which may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD3366In Part A, subjects will be randomized to receive intravenous infusion AZD3366 dose 1-7, single ascending dose (SAD). In Part A, Dose 2-7 may be adjusted based on PK data from previous cohort[s]. In Part B, subjects will be randomized to receive intravenous infusion AZD3366 dose X (a dose resulting in predicted therapeutic exposure). | Drug | AZD3366 Dose 1 Part A, AZD3366 Dose 2 Part A, AZD3366 Dose 3 Part A, AZD3366 Dose 4 Part A, AZD3366 Dose 5 Part A, AZD3366 Dose 6 Part A, AZD3366 Dose 7 Part A, AZD3366 Dose X Part B |
| PlaceboIn Part A and Part B, subjects will be randomized to receive intravenous infusion of placebo (0.9% sodium chloride solution). | Drug | Placebo Dose X Part B, Placebo Part A |
| TicagrelorAlso: BrilintaIn Part B, subjects will receive oral ticagrelor tablets. | Drug | AZD3366 Dose X Part B, Placebo Dose X Part B |
| acetylsalicylic acid (ASA)Also: Chewable aspirinIn Part B, subjects will receive oral ASA chewable tablets. | Drug | AZD3366 Dose X Part B, Placebo Dose X Part B |
Primary outcome
Number of subjects with adverse events and serious adverse events in both Part A and Part B
Time frame: From screening (Day -21) to follow-up (Day 60 for Part A and Day 50 for Part B)
Adverse events will be assessed to investigate the safety and tolerability of intravenous administration of AZD3366 in healthy subjects, healthy Japanese subjects and healthy Chinese subjects.
26 secondary outcomes
Area under plasma concentration-time curve from time zero extrapolated to infinity (AUCinf) to characterize the PK of AZD3366 in Part A
Time frame: Pre-dose, and post-dose (Day 1 to Day 60)
Terminal half life (t½λz), estimated as (ln2)/λz to characterize the PK of AZD3366 in Part A
Time frame: Pre-dose, and post-dose (Day 1 to Day 60)
Total body clearance of drug from plasma after intravascular administration (CL) to characterize the PK of AZD3366 in Part A
Time frame: Pre-dose, and post-dose (Day 1 to Day 60)
Volume of distribution at steady state from a systemic dose (Vss) to characterize the PK of AZD3366 in Part A
Time frame: Pre-dose, and post-dose (Day 1 to Day 60)
Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast) to characterize the PK of AZD3366 in Part A
Time frame: Pre-dose, and post-dose (Day 1 to Day 60)
Area under the plasma concentration-time curve from time zero to 48 hours after dosing [AUC(0-48)] to characterize the PK of AZD3366 in Part A
Time frame: Pre-dose, and post-dose (Day 1 to Day 60)
Observed maximum plasma concentration (Cmax) to characterize the PK of AZD3366 in Part A
Time frame: Pre-dose, and post-dose (Day 1 to Day 60)
Time to reach peak or maximum observed concentration following drug administration (tmax) to characterize the PK of AZD3366 in Part A
Time frame: Pre-dose, and post-dose (Day 1 to Day 60)
To study the platelet aggregration of AZD3366 in Part A
Time frame: Pre-dose, and post-dose (Day 1 to Day 60)
Assessment of the duration of capillary bleeding time (CBT) to characterize the PD of AZD3366 in Part A
Time frame: Pre-dose and post-dose (Day 1)
Collection of blood samples for the analyses of antidrug antibodies (ADAs) in both Part A and Part B
Time frame: At Day -1, Day 15, Day 23 and Day 44 in Part A, and pre-dose (Day 1), Day 15, Day 29 and Day 50 in Part B
Collection of blood samples for adenosine diphosphate-induced associated periodic-induced platelet aggregation in platelet-rich plasma to characterize the PD of AZD3366 in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
Collection of blood samples for tumor necrosis factor receptor associated periodic-induced platelet aggregation in platelet-rich plasma to characterize the PD of AZD3366 in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
CBT to characterize the PD of AZD3366 in Part B
Time frame: Pre- dose and post-dose (Day 1 and Day 3)
AUClast to characterize the plasma exposure and PD of AZD3366 in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
AUC(0-48) to characterize the plasma exposure and PD of AZD3366 in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
Cmax to characterize the plasma exposure and PD of AZD3366 in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
tmax to characterize the plasma exposure and PD of AZD3366 in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3, Day 15, Day 29, and Day 50)
AUCinf to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3)
AUClast to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3)
tmax to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3)
t½λz to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3)
Area under the plasma concentration-time curve from time zero to 12 hours after dosing [AUC(0-12)] to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3)
Cmax to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3)
Observed trough plasma concentration after the first dose (Ctrough) to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3)
Arithmetic mean of plasma concentration (C) at 12, 24, 36 and 48 hrs post-dose [Cmean (12, 24, 36, 48 hrs)] to characterize the PK of ticagrelor and ticagrelor active metabolite, AR-C124910XX in Part B
Time frame: Pre-dose and post-dose (Day 1 to Day 3)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2023.
- Derived from this study: PubMed 38804212Kardassis D, Egnell AC, Astrand M, Daniels SJ, Whatling C, Fjellstrom O, Gabrielsen A. Safety, Tolerability, and Pharmacodynamics of AZD3366 (Optimized Human CD39L3 Apyrase) Alone and in Combination With Ticagrelor and Acetylsalicylic Acid: A Phase 1, Randomized, Placebo-Controlled Study. J Am Heart Assoc. 2024 Jun 4;13(11):e033985. doi: 10.1161/JAHA.123.033985. Epub 2024 May 28.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. 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 shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Han principal investigator
PAREXEL Early Phase Clinical Unit Los Angeles 1560 Chevy Chase Drive, Suite 140 Glendale, CA 91206 United States of America
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD3366, Ticagrelor and acetylsalicylic acid (ASA) in people with Cardiovascular Disease, run by AstraZeneca at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects with adverse events and serious adverse events in both Part A and Part B (time frame: From screening (Day -21) to follow-up (Day 60 for Part A and Day 50 for Part B)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04588727, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2023.