Coronary Artery DiseasePhase 1NCT03400488

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5718 After Single and Multiple Ascending Dose Administration to Healthy Japanese Men

A Phase 1 study testing AZD5718 oral suspension in people with Coronary Artery Disease, run by AstraZeneca at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a Phase I study to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the novel compound, AZD5718 in healthy Japanese men. The results from this study will form the basis for decisions on future studies. Read more about this study

Who is it for?: Ages 18 to 50 years, men onlyHealthy volunteers can take part
Conditions the study is for: Coronary Artery Disease
What is being tested?: AZD5718 oral suspension
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 32 participants
Where: 1 siteUnited States
Study dates: 16 Jan 2018to 12 Jun 2018
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 50 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

Provision of signed and dated, written informed consent prior to any study specific procedures
Healthy male Japanese subjects aged 18-50 years with suitable veins for cannulation or repeated venipuncture. A subject will be considered as Japanese if:
both of his parents and all grandparents are Japanese,
he was born in Japan and have a Japanese passport, and
he has not lived outside Japan for more than 10 years.
Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.

Who cannot join

History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject'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 investigational medicinal product (IMP).
Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results as judged by the Investigator.
Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV).
Suspicion or known Gilbert's syndrome.

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Abnormal vital signs, after 10 minutes supine rest, at screening and check-in, defined as any of the following (repeat evaluations may be done once if the values for a subject are outside the designated range at screening and on Day -1):
Systolic blood pressure < 90 mmHg or > 140 mmHg Diastolic blood pressure < 50 mmHg or > 90 mmHg Heart rate < 45 or > 90 beats per minute (bpm)
Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities at screening and check-in in the 12-Lead ECG as considered by the Investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy. If deemed necessary, an ECG may be repeated once for each ECG measurement.
Prolonged QTcF > 450 ms or shortened QTcF < 340 ms or family history of long QT syndrome at screening and check-in. If deemed necessary, an ECG may be repeated once for each ECG measurement.
PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation) at screening and check-in. If deemed necessary, an ECG may be repeated once for each ECG measurement.
PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree atrioventricular (AV) block, or AV dissociation at screening and check-in. If deemed necessary, an ECG may be repeated once for each ECG measurement.
Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS > 110 ms. Subjects with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of e.g., ventricular hypertrophy or pre-excitation, at screening and check-in. If deemed necessary, an ECG may be repeated once for each ECG measurement.
Known or suspected history of drug abuse as judged by the Investigator.
Current smokers or those who have smoked or used nicotine products (including e-cigarettes within the previous 3 months).
History of alcohol abuse or excessive intake of alcohol as judged by the Investigator.
Positive screen for drugs of abuse or cotinine (nicotine) at screening and check-in (excluding cotinine).
History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5718.
Excessive intake of caffeine-containing drinks or food (e.g., coffee, tea, chocolate,) as judged by the Investigator.
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 non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of investigational product or longer if the medication has a long half-life.
Plasma donation within 1 month of Screening or any blood donation/blood loss > 500 mL during the 3 months prior to Screening.
Has received another new chemical entity (defined as a compound which has not been approved for marketing in the US) within 30 days or at least 5 half-lives (whichever is longer) of the first administration of investigational drug in this study. Note: subjects consented and screened, but not randomized in this study or a previous phase I study, are not excluded.
Subjects who have previously received AZD5718.
Involvement of any Astra Zeneca, PAREXEL or study site employee or their close relatives.
Judgment by the Investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the Screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
Subjects who are vegans or have medical dietary restrictions.
Subjects who cannot communicate reliably with the study team.
Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
Previous bone marrow transplant.
Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

Trial locations and contacts

1 site in 1 country.

United States1 site

Research Site
Glendale, California, 91206

Other trials in United States

About this study

Official title: A Phase 1, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5718 After Single and Multiple Ascending Dose Administration to Healthy Japanese Men

Read the detailed description

This study will be a Phase 1, randomized, single-blind, placebo-controlled, single and multiple ascending dose sequential group design in up to 48 healthy male Japanese subjects, performed at a single study center. The planned number of cohorts is 4 but up to 6 cohorts may be included if the Safety Review Committee (SRC) considers it necessary to repeat a dose level or if additional dose steps are required. Screening will be completed between Days -28 and -1. Primarily gradual escalation of the dose will be conducted with the oral suspension. Eight subjects will participate in each cohort. Four ascending dose levels are planned. Within each cohort 6 subjects will be randomised to receive AZD5718 and 2 subjects randomised to receive placebo. Each subject will receive one dose of AZD5718 or placebo on the first dosing day (Day 1, single ascending dose, SAD) and on Days 3 to 10 (multiple ascending dose, MAD). On Day 2 no dose will be given to the subject. In total each subject will receive 9 doses. Dosing for each ascending dose cohort will proceed after the SRC has evaluated the safety, tolerability and other relevant data of a completed cohort. The subjects will stay at the study site until 48 hours post-dose and will return 7 to 10 days after dosing for a follow-up visit. Each subject will be involved in the study for 7 weeks.

Conditions: Coronary Artery Disease
Being tested: AZD5718 oral suspension, Placebo matching AZD5817 oral suspension
Keywords: Coronary Artery Disease,, Cardiovascular disease (CAD),, 5-lipoxygenase activating protein (FLAP) inhibitor,, Leukotrienes.
Medical subject headings: Coronary Artery Disease, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD5718 oral suspensionDrug
In all cohorts, randomized subjects will receive orally AZD5718 oral suspension SAD (60 mg) on Day 1 and MAD (180 mg, 360 mg and 600 mg) from Days 3 to 10. On Day 2, no dose will be given. In total each subject will receive 9 doses of AZD5718.
Placebo matching AZD5817 oral suspensionOther
In all cohorts, randomized subjects will receive orally placebo matching AZD5718 oral suspension on Day 1 and from Days 3 to 10. On Day 2, no dose will be given.

Study groups in NCT03400488
Study group	Role	What they receive
AZD5718	Experimental	Randomized subjects will receive orally once daily dose of AZD5718 oral suspension on Day 1 (SAD) and MAD from Days 3 to 10. On Day 2, no dose will be given. These procedures will be repeated in all cohorts. Receives: Drug: AZD5718 oral suspension
Placebo	Placebo comparator	Randomized subjects will receive orally once daily dose of placebo matching AZD5718 oral suspension on Day 1 (SAD) and MAD form Days 3 to 10. On Day 2, no dose will be given. These procedures will be repeated in all cohorts. Receives: Other: Placebo matching AZD5817 oral suspension

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of patients with Adverse Events (AEs) due to AZD5817
To assess the adverse events as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. Adverse Events will be collected from the start of randomization throughout the treatment period up to and including the follow-up visit. Serious adverse events (SAEs) will be recorded from the time of informed consent.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Supine vital sign (Systolic Blood pressure [BP])
To assess the vital sign as a variable of safety and tolerability variable of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Supine vital sign (pulse rate)
To assess the vital sign as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Number of participants with abnormal findings in electrocardiograms (ECGs) (safety ECGs, digital ECGs [dECG])
To assess any clinically important abnormalities in the cardiovascular system functioning as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. A 12-lead 10-second safety ECG will be performed with the Schiller Cardiovit CS-200 recorder immediately following all scheduled dECGs. 12-lead continuous dECG will be recorded over at least 5 minutes with the Schiller Cardiovit CS-200 recorder and transmitted to the AstraZeneca central dECG repository, according to AstraZeneca ECG Center´s standard procedures for settings, recording, and transmission of dECGs. For dECG, QTcF (QT interval corrected for heart rate using Fridericia's formula) will be calculated as QTcF =(QT*(RR/1000)^(-1/3)), where RR (the time between corresponding points on 2 consecutive R waves on ECG) is presented in milliseconds. Heart rate (HR) will also be calculated, based on the RR interval.
Measured: From baseline up to follow-up (7 to 10 days post-(final) dose). For dECG: Days 1 to 12
Number of participants with abnormal cardiac telemetry
To assess any clinically important abnormalities in the cardiovascular system functioning (heart beat/rythm) using 2-lead real-time telemetry ECG as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. The telemetry monitoring system will be reviewed by the Investigator or research nurse and paper printouts of any clinically important events will be stored as source data.
Measured: From baseline up to Day 10
Number of participants with abnormal findings in physical examinations
To assess any clinically important abnormal findings in physical conditions as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. The complete physical examinations include an assessment of the general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. The brief physical examinations include an assessment of the general appearance, skin, cardiovascular system, respiratory and abdomen. Any new or aggravated clinically relevant abnormal medical finding at a physical examination as compared with the baseline assessment will be reported as an adverse event.
Measured: From baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (leukocyte count)
To assess the leukocyte count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Supine vital sign (diastolic BP)
To assess the vital sign as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (sodium)
To assess the clinical chemistry value (sodium) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Urinalysis (glucose)
To assess urinalysis (glucose) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (Red blood cell [RBC] count)
To assess the RBC count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (Hemoglobin [Hb])
To assess the Hb as a criterion of safety and tolerability variable of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (Hematocrit [HCT])
To assess the HCT as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (Mean corpuscular volume [MCV])
To assess the MCV as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (Mean corpuscular hemoglobin [MCH])
To assess the MCH as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (Mean corpuscular hemoglobin concentration [MCHC])
To assess the MCHC as a variable of safety and tolerability variable of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (potassium)
To assess the clinical chemistry value (potassium) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (urea)
To assess the clinical chemistry value (urea) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (creatinine)
To assess the clinical chemistry value (creatinine) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (albumin)
To assess the clinical chemistry value (albumin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (calcium)
To assess the clinical chemistry value (calcium) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (phosphate)
To assess the clinical chemistry value (phosphate) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (glucose (fasting))
To assess the clinical chemistry value (glucose (fasting)) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (insulin)
To assess the clinical chemistry value (insulin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (fibrinogen)
To assess the clinical chemistry value (fibrinogen) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (thyroid-stimulating hormone)
To assess the clinical chemistry value (thyroid-stimulating hormone) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Urinalysis (blood)
To assess urinalysis (blood) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses. If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, white blood cell [WBC], casts [cellular, granular, hyaline]).
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Urinalysis (protein)
To assess urinalysis (protein) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses. If urinalysis is positive for protein, a microscopy test will be performed to assess RBC, WBC, casts [cellular, granular, hyaline]).
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Urinalysis (urine creatinine)
To assess urinalysis (urine creatinine) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (Differential Count)
To assess the differential count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (Platelets)
To assess the platelets as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Hematology (Reticulocytes absolute count)
To assess the reticulocytes absolute count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (High sensitivity-C-reactive protein [CRP])
To assess the clinical chemistry value (CRP) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (Free T4)
To assess the clinical chemistry value (Free T4) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (Alkaline phosphatase [ALP])
To assess the clinical chemistry value (ALP) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (Alanine aminotransferase [ALT])
To assess the clinical chemistry value (ALT) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (Aspartate aminotransferase [AST])
To assess the clinical chemistry value (AST) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (Gamma glutamyl transpeptidase [GGT])
To assess the clinical chemistry value (GGT) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (Total Bilirubin)
To assess the clinical chemistry value (total bilirubin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (Unconjugated bilirubin)
To assess the clinical chemistry value (unconjugated bilirubin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (Glutamate dehydrogenase)
To assess the clinical chemistry value (glutamate dehydrogenase) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
Laboratory assessment: Clinical chemistry (Lactate dehydrogenase [LDH])
To assess the clinical chemistry value (LDH) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Measured: Change from baseline up to follow-up (7 to 10 days post-(final) dose)

Secondary outcomes (20)

Plasma PK assessment: Observed maximum plasma concentration (Cmax) assessment for AZD5817 after single and repeated oral dosing
To assess Cmax of AZD5718 after single and repeated oral dosing.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Time to reach peak or maximum observed concentration following drug administration (tmax) assessment for AZD5817 after single and repeated oral dosing
To assess tmax of AZD5718 after single and repeated oral dosing.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Terminal rate constant (λZ) assessment for AZD5817 after single and repeated oral dosing
To assess λZ of AZD5718 after single and repeated oral dosing. λZ will be estimated by log-linear least-squares regression of the terminal part of the concentration-time curve.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Terminal half-life (t½λz) assessment for AZD5817 after single and repeated oral dosing
To assess t½λz of AZD5718 after single and repeated oral dosing. t½λz will be estimated as (ln2)/λZ.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Area under the plasma concentration-time curve from time zero to 24 hours after dosing (AUC(0-24)) assessment for AZD5817 after single and repeated oral dosing
To assess AUC(0-24) of AZD5718 after single and repeated oral dosing.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUC(0-last)) assessment for AZD5817 after single and repeated oral dosing
To assess AUC(0-last) of AZD5718 after single and repeated oral dosing.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Area under the plasma concentration-curve over the dosing interval (AUC(0-τ)) assessment for AZD5817 after single and repeated oral dosing
To assess AUC(0-τ) of AZD5718 after single and repeated oral dosing.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Area under the concentration-time curve from time zero extrapolated to infinity (AUC) assessment for AZD5817 after single and repeated oral dosing
To assess AUC of AZD5718 after single and repeated oral dosing. AUC is estimated by AUC(0-last) + Clast/λZ where Clast is the last observed quantifiable concentration.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) assessment for AZD5817 after single and repeated oral dosing
To assess CL/F of AZD5718 after single and repeated oral dosing.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Mean Residence Time (MRT) assessment for AZD5817 after single and repeated oral dosing
To assess MRT of AZD5718 after single and repeated oral dosing.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Apparent volume of distribution for parent drug at terminal phase (extravascular administration), (Vz/F) assessment for AZD5817 after single and repeated oral dosing
To assess Vz/F of AZD5718 after single and repeated oral dosing. Vz/F will be estimated by dividing the apparent clearance (CL/F) by λZ.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Observed minimum concentration, (Cmin) assessment for AZD5817 after single and repeated oral dosing (Day 10)
To assess Cmin of AZD5718 after single and repeated oral dosing. Cmin will be taken directly from the individual concentration-time curve.
Measured: Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Observed average concentration (Cavg) assessment for AZD5817 after single and repeated oral dosing (Day 10)
To assess Cavg of AZD5718 after single and repeated oral dosing. Cavg will be taken directly from the individual concentration-time curve.
Measured: Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Accumulation ratio (Rac Cmax) assessment for AZD5817 after single and repeated oral dosing
To assess Rac Cmax of AZD5718 after single and repeated oral dosing. Rac Cmax will be calculated as Cmax Day 10/ Cmax Day 1.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Accumulation ratio (Rac AUC) assessment for AZD5817 after single and repeated oral dosing
To assess Rac AUC of AZD5718 after single and repeated oral dosing. Rac AUC will be calculated as AUCτ Day 10/ AUCτ Day 1.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Temporal change parameter in systemic exposure (TCP) assessment for AZD5817 after single and repeated oral dosing
To assess TCP of AZD5718 after single and repeated oral dosing. TCP will be calculated as AUCτDay 10/AUCDay 1.
Measured: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Urine PK assessment: Cumulative amount of unchanged drug excreted in urine from time zero to the last sampling interval (Ae(0-last)) assessment for AZD5817 after single and repeated oral dosing
To assess Ae(0-last) of AZD5718 after single and repeated oral dosing.
Measured: Day 10 pooled 0-3, 3-6, 6-9, 9-12 hours and 12-24 hours urine
Urine PK assessment: Fraction of dose excreted unchanged into the urine from time zero to the last sampling interval measured time point for an analyte (Fe(0-last)) assessment for AZD5817 after single and repeated oral dosing
To assess Fe(0-last) of AZD5718 after single and repeated oral dosing. Fe(0-last) will be estimated by dividing Ae(0-last) by dose.
Measured: Day 10 pooled 0-3, 3-6, 6-9, 9-12 hours and 12-24 hours urine
Urine PK assessment: Renal clearance of drug from plasma (CLR) assessment for AZD5817 after single and repeated oral dosing
To assess CLR of AZD5718 after single and repeated oral dosing. CLR will be estimated by dividing Ae(0-last) by AUC(0-t)).
Measured: Day 10 pooled 0-3, 3-6, 6-9, 9-12 hours and 12-24 hours urine
PD parameter: urine Leukotriene E4 (LTE4) assessment for AZD5817 after single and repeated oral dosing
To evaluate the PD of AZD5718, by assessment of urine LTE4 (u-LTE4), after single and repeated oral dosing.
Measured: Day -1 (spot sample), Day 1 and Day 10 spot sample pre-dose and pooled 0-3, 3-6, 6-9 and 9-12 hours urine, spot sample at 24, 36 hours post-dose, Day 3-9: spot sample pre-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jan 201812 Jun 2018

First posted17 Jan 2018
Study start16 Jan 2018
Primary completion12 Jun 2018
Study completion12 Jun 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Coronary Artery 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: Single blind
Who is masked: Participant
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03400488
Sponsor's protocol ID: D7550C00004
Status last verified: Jun 2018
First submitted: 12 Dec 2017
Last updated: 15 Jun 2018
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Coronary Artery Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Jun 2018. 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 AZD5718 After Single and Multiple Ascending Dose Administration to Healthy Japanese Men
ClinicalTrials.gov ID: NCT03400488
Acronym / sponsor ID: D7550C00004
Conditions: Coronary Artery Disease
Keywords: Coronary Artery Disease,, Cardiovascular disease (CAD),, 5-lipoxygenase activating protein (FLAP) inhibitor,, Leukotrienes.
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 16 Jan 2018 (actual)
Primary completion: 12 Jun 2018 (actual)
Study completion: 12 Jun 2018 (actual)
First posted: 17 Jan 2018 (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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
AZD5718	Experimental	Drug: AZD5718 oral suspensionRandomized subjects will receive orally once daily dose of AZD5718 oral suspension on Day 1 (SAD) and MAD from Days 3 to 10. On Day 2, no dose will be given. These procedures will be repeated in all cohorts.
Placebo	Placebo comparator	Other: Placebo matching AZD5817 oral suspensionRandomized subjects will receive orally once daily dose of placebo matching AZD5718 oral suspension on Day 1 (SAD) and MAD form Days 3 to 10. On Day 2, no dose will be given. These procedures will be repeated in all cohorts.

Who may qualify

Ages: 18 to 50 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Provision of signed and dated, written informed consent prior to any study specific procedures
Healthy male Japanese subjects aged 18-50 years with suitable veins for cannulation or repeated venipuncture. A subject will be considered as Japanese if:
Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.

Key exclusion criteria (32 listed)

History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject'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 investigational medicinal product (IMP).
Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results as judged by the Investigator.
Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV).

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
AZD5718 oral suspensionIn all cohorts, randomized subjects will receive orally AZD5718 oral suspension SAD (60 mg) on Day 1 and MAD (180 mg, 360 mg and 600 mg) from Days 3 to 10. On Day 2, no dose will be given. In total each subject will receive 9 doses of AZD5718.	Drug	AZD5718
Placebo matching AZD5817 oral suspensionIn all cohorts, randomized subjects will receive orally placebo matching AZD5718 oral suspension on Day 1 and from Days 3 to 10. On Day 2, no dose will be given.	Other	Placebo

Primary outcome

Number of patients with Adverse Events (AEs) due to AZD5817
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the adverse events as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. Adverse Events will be collected from the start of randomization throughout the treatment period up to and including the follow-up visit. Serious adverse events (SAEs) will be recorded from the time of informed consent.
Supine vital sign (Systolic Blood pressure [BP])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the vital sign as a variable of safety and tolerability variable of AZD5718 following oral administration of single and multiple ascending doses.
Supine vital sign (pulse rate)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the vital sign as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Number of participants with abnormal findings in electrocardiograms (ECGs) (safety ECGs, digital ECGs [dECG])
Time frame: From baseline up to follow-up (7 to 10 days post-(final) dose). For dECG: Days 1 to 12
To assess any clinically important abnormalities in the cardiovascular system functioning as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. A 12-lead 10-second safety ECG will be performed with the Schiller Cardiovit CS-200 recorder immediately following all scheduled dECGs. 12-lead continuous dECG will be recorded over at least 5 minutes with the Schiller Cardiovit CS-200 recorder and transmitted to the AstraZeneca central dECG repository, according to AstraZeneca ECG Center´s standard procedures for settings, recording, and transmission of dECGs. For dECG, QTcF (QT interval corrected for heart rate using Fridericia's formula) will be calculated as QTcF =(QT*(RR/1000)^(-1/3)), where RR (the time between corresponding points on 2 consecutive R waves on ECG) is presented in milliseconds. Heart rate (HR) will also be calculated, based on the RR interval.
Number of participants with abnormal cardiac telemetry
Time frame: From baseline up to Day 10
To assess any clinically important abnormalities in the cardiovascular system functioning (heart beat/rythm) using 2-lead real-time telemetry ECG as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. The telemetry monitoring system will be reviewed by the Investigator or research nurse and paper printouts of any clinically important events will be stored as source data.
Number of participants with abnormal findings in physical examinations
Time frame: From baseline up to follow-up (7 to 10 days post-(final) dose)
To assess any clinically important abnormal findings in physical conditions as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. The complete physical examinations include an assessment of the general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. The brief physical examinations include an assessment of the general appearance, skin, cardiovascular system, respiratory and abdomen. Any new or aggravated clinically relevant abnormal medical finding at a physical examination as compared with the baseline assessment will be reported as an adverse event.
Laboratory assessment: Hematology (leukocyte count)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the leukocyte count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Supine vital sign (diastolic BP)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the vital sign as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (sodium)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (sodium) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Urinalysis (glucose)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess urinalysis (glucose) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Hematology (Red blood cell [RBC] count)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the RBC count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Hematology (Hemoglobin [Hb])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the Hb as a criterion of safety and tolerability variable of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Hematology (Hematocrit [HCT])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the HCT as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Hematology (Mean corpuscular volume [MCV])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the MCV as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Hematology (Mean corpuscular hemoglobin [MCH])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the MCH as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Hematology (Mean corpuscular hemoglobin concentration [MCHC])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the MCHC as a variable of safety and tolerability variable of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (potassium)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (potassium) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (urea)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (urea) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (creatinine)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (creatinine) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (albumin)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (albumin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (calcium)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (calcium) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (phosphate)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (phosphate) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (glucose (fasting))
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (glucose (fasting)) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (insulin)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (insulin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (fibrinogen)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (fibrinogen) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (thyroid-stimulating hormone)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (thyroid-stimulating hormone) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Urinalysis (blood)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess urinalysis (blood) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses. If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, white blood cell [WBC], casts [cellular, granular, hyaline]).
Laboratory assessment: Urinalysis (protein)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess urinalysis (protein) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses. If urinalysis is positive for protein, a microscopy test will be performed to assess RBC, WBC, casts [cellular, granular, hyaline]).
Laboratory assessment: Urinalysis (urine creatinine)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess urinalysis (urine creatinine) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Hematology (Differential Count)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the differential count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Hematology (Platelets)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the platelets as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Hematology (Reticulocytes absolute count)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the reticulocytes absolute count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (High sensitivity-C-reactive protein [CRP])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (CRP) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (Free T4)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (Free T4) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (Alkaline phosphatase [ALP])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (ALP) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (Alanine aminotransferase [ALT])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (ALT) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (Aspartate aminotransferase [AST])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (AST) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (Gamma glutamyl transpeptidase [GGT])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (GGT) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (Total Bilirubin)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (total bilirubin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (Unconjugated bilirubin)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (unconjugated bilirubin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (Glutamate dehydrogenase)
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (glutamate dehydrogenase) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.
Laboratory assessment: Clinical chemistry (Lactate dehydrogenase [LDH])
Time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)
To assess the clinical chemistry value (LDH) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

20 secondary outcomes

Plasma PK assessment: Observed maximum plasma concentration (Cmax) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Time to reach peak or maximum observed concentration following drug administration (tmax) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Terminal rate constant (λZ) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Terminal half-life (t½λz) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Area under the plasma concentration-time curve from time zero to 24 hours after dosing (AUC(0-24)) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUC(0-last)) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Area under the plasma concentration-curve over the dosing interval (AUC(0-τ)) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Area under the concentration-time curve from time zero extrapolated to infinity (AUC) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Mean Residence Time (MRT) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Apparent volume of distribution for parent drug at terminal phase (extravascular administration), (Vz/F) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Plasma PK assessment: Observed minimum concentration, (Cmin) assessment for AZD5817 after single and repeated oral dosing (Day 10)
Time frame: Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Observed average concentration (Cavg) assessment for AZD5817 after single and repeated oral dosing (Day 10)
Time frame: Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Accumulation ratio (Rac Cmax) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Accumulation ratio (Rac AUC) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose
Plasma PK assessment: Temporal change parameter in systemic exposure (TCP) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 1 and Day 10: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32 and 48 hours (Day 3 pre-dose) post-dose, Day 4-9 pre morning dose
Urine PK assessment: Cumulative amount of unchanged drug excreted in urine from time zero to the last sampling interval (Ae(0-last)) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 10 pooled 0-3, 3-6, 6-9, 9-12 hours and 12-24 hours urine
Urine PK assessment: Fraction of dose excreted unchanged into the urine from time zero to the last sampling interval measured time point for an analyte (Fe(0-last)) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 10 pooled 0-3, 3-6, 6-9, 9-12 hours and 12-24 hours urine
Urine PK assessment: Renal clearance of drug from plasma (CLR) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day 10 pooled 0-3, 3-6, 6-9, 9-12 hours and 12-24 hours urine
PD parameter: urine Leukotriene E4 (LTE4) assessment for AZD5817 after single and repeated oral dosing
Time frame: Day -1 (spot sample), Day 1 and Day 10 spot sample pre-dose and pooled 0-3, 3-6, 6-9 and 9-12 hours urine, spot sample at 24, 36 hours post-dose, Day 3-9: spot sample pre-dose

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 15 Jun 2018.

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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, Dr principal investigator

PAREXEL Early Phase Clinical Unit-Los Angeles

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 AZD5718 oral suspension in people with Coronary Artery 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 7 inclusion and 32 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 15 Jun 2018. 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 patients with Adverse Events (AEs) due to AZD5817 (time frame: Change from baseline up to follow-up (7 to 10 days post-(final) dose)). The study lists 42 primary outcomes in all. 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 NCT03400488.

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 15 Jun 2018.