A Study to Assess the Safety and Tolerability of Single Doses of AZD4076 in Healthy Male Subjects

Korábbi kezelés

• Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening
• Positive screen for drugs of abuse or cotinine (nicotine) at screening or admission to the unit or positive screen for alcohol on admission to the unit prior to the administration of IMP
• Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the 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 two weeks prior to the administration of IMP or longer if the medication has a long half-life
• Plasma donation within one 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) within 3 months of the administration of IMP in this study. The period of exclusion begins three months after the final dose or one month after the last visit whichever is the longest.
  • Note: Subjects consented and screened, but not randomized in this study or a previous phase I study, are not excluded.
• Previous bone marrow transplant

Más betegség

• History or presence 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
• History or presence of hepatic or renal disease, or any other condition known to interfere with distribution, metabolism, or excretion of drugs
• History or presence of significant neurological or psychiatric disease/mental illness (as judged by the investigator)
• Suspicion of or known Gilbert's syndrome based on liver function tests
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the administration of IMP
• Known or suspected history of drug abuse, as judged by the investigator
• History of alcohol abuse or excessive intake of alcohol, as judged by the investigator
• 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 AZD4076 tetracosasodium

Laborértékek

• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV)
• Serum Creatinine greater than the ULN.
• Platelet count outside the normal range.
• AST, ALT, or GGT greater than the ULN.
• Any clinically significant abnormalities 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
• Prolonged QTcF > 450 ms or shortened QTcF < 340 ms or family history of long QT syndrome
• Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection

Egyéb

• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the investigator
• Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:
  • Systolic BP (SBP) < 90mmHg or ≥ 140 mmHg
  • Diastolic BP (DBP) < 50mmHg or ≥ 90 mmHg
  • Pulse < 45 or > 85 beats per minute (bpm)
• PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation)
• PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation
• 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
• Excessive intake of caffeine containing drinks or food (e.g., coffee, tea), as judged by the investigator
• Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order
• 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 investigator
  • In addition, any of the following is regarded as a criterion for exclusion from the genetic research:

• Provision of signed and dated, written informed consent prior to any study specific procedures
• Healthy male subjects aged 18 - 50 years with suitable veins for cannulation or repeated venipuncture
• 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