A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5718 After Single and Multiple Ascending Dose Administration to Healthy Male Subjects
Status and phase
Conditions
Treatments
Details and patient eligibility
About
This is a phase I, randomised, single-blind, placebo-controlled, first-in-human (FIH) single and multiple ascending dose study consisting of two parts (Part A [SAD] and Part B [MAD]) to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5718 in healthy male subjects
Full description
This is a phase I, randomised, single-blind, placebo-controlled, first-in-human (FIH) single and multiple ascending dose study consisting of two parts (Part A [SAD] and Part B [MAD]) to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5718 in healthy male subjects
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
- Provision of signed and dated, written informed consent prior to any study specific procedures
- Healthy male subjects aged 18 - 50 years, inclusive, with suitable veins for cannulation or repeated venepuncture
- 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 research
Exclusion criteria
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History of any clinically significant 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
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History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
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Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the administration of investigational medicinal product (IMP)
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Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results at screening and check-in, as judged by the investigator, including:
- Alanine aminotransferase (ALT) > upper limit of normal (ULN);
- Aspartate aminotransferase (AST) > ULN;
- Bilirubin (total) > ULN; and
- Gamma glutamyl transpeptidase (GGT) > ULN
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Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV)
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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:
- Systolic blood pressure(BP) (SBP) < 90mmHg or ≥ 140 mmHg;
- Diastolic BP (DBP) < 50mmHg or ≥ 90 mmHg; and
- Pulse < 45 or > 85 beats per minute (bpm)
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Any clinically significant abnormalities (at screening and check-in) in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities 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
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Prolonged QTcF (QT interval corrected for heart rate using Fridericia's formula) > 450 ms or shortened QTcF < 340 ms or family history of long QT syndrome, at screening and check-in
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PR(PQ) interval (ECG interval measured from the onset of the P wave to the onset of the QRS complex) 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
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PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation, at screening and check-in
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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, for example, ventricular hypertrophy or pre-excitation, at screening and check-in
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Known or suspected history of drug abuse, as judged by the investigator
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Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening
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Any history of alcohol abuse or excessive intake of alcohol, as judged by the investigator
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Positive screen for drugs of abuse, alcohol or cotinine (nicotine) at screening or admission to the unit
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History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5718
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Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the investigator
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Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP
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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 administration of IMP or longer if the medication has a long half-life
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Plasma donation within 1 month of screening or any blood donation/blood loss > 500 mL during the 3 months prior to screening
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Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the administration of IMP in this study. The period of exclusion is 3 months after the final dose from a previous study
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Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order
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Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives
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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
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Subjects who are vegans or have medical dietary restrictions
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Subjects who cannot communicate reliably with the investigator
In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
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Previous bone marrow transplant
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Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection
Trial design
Primary purpose
Allocation
Interventional model
Masking
96 participants in 17 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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