A Phase I, randomised, double blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of single and repeat doses of AMP945 administered orally to healthy adult volunteers

INTERVENTION: Part A, single ascending doses: Oral AMP945 capsules administered once with water to in‐patients after an overnight fast of 10 hours. Dosing compliance will be assessed by hand and mouth checks. The starting dose (Cohort 1) will be 15mg, and subsequent doses (Cohorts 2 to 5) will be decided based on safety and pharmacokinetic data. The maximum dose will not exceed 1000mg. Part B: Oral AMP945 capsules administered once with water to in‐patients immediately after a high fat meal (at least 50% fat) following an an overnight fast of 10 hours. Dosing compliance will be assessed by hand and mouth checks. The dose will be decided based on Part A data, and the relevant Part A cohort will return at least 7 days after dosing for Part B. Part C, multiple ascending doses: Oral AMP945 capsules administered with water to in‐patients after an overnight fast of 10 hours, once a day for 7 days. Dosing compliance will be assessed by hand and mouth checks. The starting dose will be decided based on Part A and Part B data, and subsequent doses decided based on safety and pharmacokinetic data CONDITION: Cancer ‐ Pancreatic Pancreatic cancer;Idiopathic pulmonary fibrosis; ; Pancreatic cancer ; Idiopathic pulmonary fibrosis Respiratory ‐ Other respiratory disorders / diseases PRIMARY OUTCOME: Safety and tolerability will be assessed by vital signs, clinical safety labs, electrocardiograms (ECGs), physical exams and adverse events.[Part A and Part B: Dosing on Day 1, daily in‐patient monitoring for 3 days plus follow up visit on Day 7; Part C: Dosing on Day 1, daily in‐patient monitoring for 8 days plus follow up visit on Day 14] SECONDARY OUTCOME: Plasma pharmacokinetics of AMP945, including AUC, Tmax, Cmax, T1/2[Part A and Part B: At 15, 30 minutes and 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post dose ; ; Part C: At 15, 30 minutes and 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post dose, on Day 1 and Day 7, prior to drug administration on Days 3 to 6, and on Day 14.] Urine pharmacokinetics of AMP945, including absorption and elimination[Part A and Part B: Dosing on Day 1, pooled samples 0‐4, 4‐12, 12‐24 hours post dose, and a spot urine sample at 24, 36, and 48 hours post dose, and on Day 7 ; ; Part C: Dosing on Day 1, pooled samples samples 0‐4, 4‐12, 12‐24 hours post dose, on Day 1 and Day 14, and spot samples prior to drug administration on Days 2 to 6, and on Day 14.] INCLUSION CRITERIA: • Provide written informed consent prior to any study procedures and agree to adhere to all protocol requirements. ‐ Are aged 18 to 50 years old at the time of consent. ‐ Are in good general health without clinically significant medical history. ‐ Weigh at least 50kg and have a body mass index at least 18 and less than 30kg/m2. ‐ Agree to practice effective contraception during the study period and for 3 months after their last dose of study drug ‐ Provision of written informed consent