A Randomised, Placebo Controlled, Double-Blind, Single Ascending Dose and Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous Doses of ATL1103 in Healthy Adult Male Subjects

Exclusion Criteria26

• Volunteers with any of the following criteria will not be eligible for participation in this study:
• Hypersensitivity. History of allergy and/or hypersensitivity to any of the stated ingredients of the formulations. A known hypersensitivity to lidocaine or all surgical dressings which may be used in the study procedures.
• Medical Conditions
• a) History of clinically significant gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease or haematological disorders.
• b) Any history of clinically significant cardiac arrhythmias or the presence of clinically significant abnormalities on ECG at Screening.
• c) Any evidence or history of hypotension or hypertension in the opinion of the PI following repeat assessment.
• d) Any history of asthma during the last 10 years.
• e) A calculated creatinine clearance of less than 75 mL/min.
• f) Any predisposing condition that in the opinion of the Investigator might interfere with the absorption, distribution, metabolism and/or excretion of drugs.
• g) History of abnormal bleeding tendencies or thrombophlebitis unrelated to venepuncture or intravenous cannulation, or a history of Hepatitis B, a positive test for Hepatitis B surface antigen, a history of Hepatitis C, a positive test for Hepatitis C antibody, a history of HIV infection or demonstration of HIV antibodies.
• h) Inability to tolerate repeated venepuncture.
• Laboratory Status. Any evidence of organ dysfunction, or any deviation in clinical laboratory values which is confirmed upon re-examination to be clinically significant (i.e., in the opinion of the PI would jeopardise the safety of the subject or impact on the validity of the study results), including a liver function test (LFT) > upper limit of normal (ULN). Total bilirubin levels > 1.5 x ULN will be allowed if associated with Gilbert’s syndrome.
• Ethanol Use. Regular drinkers of more than four (4) units of alcohol daily (1 unit = 300 mL beer, 1 glass wine, 1 measure spirit) or those who may have difficulty abstaining from alcohol during the 48 hours prior to dose administration and until completion of blood sampling on Day 2 for the single-dose cohorts (Stage A) or Day 7 for the multiple-dose cohorts (Stage B).
• Drug and Alcohol Abuse. History of, or current evidence of, abuse of alcohol or any drug substance, licit or illicit, or positive urine drug and alcohol screen for drugs of abuse and alcohol.
• Smoking. Current smoker of not more than 5 cigarettes or equivalent per day prior to commencing the study, unable to completely stop smoking during the study.
• Medication
• a) Difficulty in abstaining from any prescription medications for 14 days prior to dose administration and for the duration of the study.
• b) Difficulty in abstaining from over-the-counter (OTC) medications or herbal supplements for seven days prior to dose administration and for the duration of the study.
• Administration site. Any tattoos in the anterior abdominal area which, in the opinion of the Investigator would preclude accurate local tolerance assessments of injection sites.
• Xanthine Use. Difficulty in abstaining from food and/or beverages that contain caffeine or other xanthines
• (e.g., coffee, tea, cola and chocolate) during the 24 hours prior to dose administration and whilst confined at the clinical facility.
• Psychiatric or Psychological Disorder. History of any psychiatric illness or psychological disorder which may impair the ability to provide written informed consent or participate in the study.
• Protocol Compliance. Poor compliers or those unlikely to attend the Unit.
• Recent Study Participation. Receipt of any drug as part of a research study within 30 days of initial dose administration in this study.
• Blood Donation. Standard blood donation (usually 550 mL) within the 12-week period before dose administration.
• Dietary Habits. Unusual dietary habits, including vegetarian diets and excessive or unusual vitamin intakes.