A two-part study to assess the effectiveness, safety, and blood levels of repeat doses of inhaled ETD001 in people with cystic fibrosis

INTERVENTION: Part A (safety and tolerability in participants with cystic fibrosis): Eight participants will receive 13 doses of ETD001 4.5 mg or placebo as an oral inhalation twice a day over 7 days, twice daily doses on Days 1 to 6 and a single dose on the morning of Day 7. Si Xparticipants will receive active ETD001 and 2 will receive placebo. Allocation of participants to treatment type will be coordinated using a centralised interactive response technology (IRT) system. Part B (safety and efficacy in participants with cystic fibrosis): Twenty‐two participants will be required to complete two 28 day treatment periods, twice daily doses of ETD001 4.5 mg will be administered in one treatment period and twice daily doses of placebo will be administered in the other treatment period. In each treatment period a total 55 doses of ETD001 4.5 mg or placebo will be administered as an oral inhalation over 28 days, twice daily doses on Days 1 to 27 and a single morning dose on the morning of Day 28. The order in which participants receive ETD001 and placebo will be coordinated using the centralised IRT system. All study participants, in both Part A and Part B, will return to the study centre for a safety follow up appointment 3 weeks (21 days) after completing the final treatment period. A review of safety data from Part A will be completed by an independent data safety monitoring board before the start of Part B. Participants who have completed Part A may also take part in Part B. CONDITION: Cystic Fibrosis ; Respiratory PRIMARY OUTCOME: Part A; 1. Number of participants reporting adverse events (AE) – baseline to follow up (approximately 28 days); 2. Number of participants who discontinue due to an AE – baseline to follow up (approximately 28 days); 3. Number of participants with vital sign abnormalities as assessed by measuring systolic and diastolic blood pressure, heart rate, respiration rate, temperature and peripheral oxygen saturation – baseline to follow up (approximately 28 days); 4. Number of participants with spirometry abnormalities as measured using a spirometer – baseline to follow up (approximately 28 days); 5. Number of participants with laboratory test abnormalities measured using biological samples – baseline to follow up (approximately 28 days); 6. Number of participants with electrocardiogram (ECG) abnormalities measured using 12‐Lead ECG recordings – baseline to follow up (approximately 28 days) ; ; Part B ; 7. Absolute change in percent predicted forced expiratory flow volume over 1 second (ppFEV1) measured using a spirometer from Day 1 to Day 28 in Treatment Period 1 and Treatment Period 2 (approximately 84 days); SECONDARY OUTCOME: Part A; 1. Plasma concentrations and derived PK parameters (Cmax, Tma X, AUC(0‐t), AUC(0‐tau), AUC(0‐inf), Tlast, ?z, T1/2, CL/F, Vz/F) of ETD001 measured in blood samples collected at specific timepoints pre‐dose and post‐dose on Day 1 and up to 21 days after the final dose of study medication (approximately 28 days); 2. Urine concentrations (amount excreted in urine (Ae); fraction of dose excreted (Fe), renal clearance (CL)), of ETD001 measured in urine samples collected at specific timepoints pre‐dose and up to 6 hours post‐dose on Day 1 (1 day); ; Part B; 3. Relative change in ppFEV1 measured using a spirometer from Day 1 to Day 28 in Treatment Period 1 and Treatment Period 2 (approximately 84 days) ; 4. Absolute change in other lung function parameters (FVC, FEV1/FVC ratio and FEF25‐75) measured using a spirometer from Day 1 to Day 28 in Treatment Period 1 and Treatment Period 2 (approximately 84 days) ; 5. Number of participants reporting adverse events (AE) – baseline to follow up (approximately 105 days); 6. Number of participants who discontinue due to an AE – baseline to follow up (approximately 105 days); 7. Number of participants with vital sign abnormalities as assessed by measuring systolic and diastolic blood pressure, heart rate, respiration rate, temperature and peripheral oxygen saturation from Day 1 to Day 28 in Treatment Period 1 and Treatment Period 2 and up to 21 days after the final dose of study medication (approximately 105 days); 8. Number of participants with laboratory test abnormalities measured using biological samples from Day 1 to Day 28 in Treatment Period 1 and Treatment Period 2 and up to 21 days after the final dose of study medication (approximately 105 days); 9. Number of participants with electrocardiogram (ECG) abnormalities measured using 12‐Lead ECG recordings from Day 1 to Day 28 in Treatment Period 1 and Treatment Period 2 and up to 21 days after the final dose of study medication (approximately 105 days); 10. Change in Cystic Fibrosis Questionnaire – Revised (CFQ‐R) from Day 1 to Day 28 in Treatment Period 1 and Treatment Period 2 (approximately 84 days); 11. Population PK characteristics and model generated individual PK parameters (Cmax, Tma X, AUC(0‐t), AUC(0‐tau), AUC(0‐inf), Tlast, ?z, T1/2, CL/F, Vz/F) of ETD001 measured in blood samples collected at specific timepoints pre‐dose and post‐dose on Day 1 and up to 21 days after the final dose of study medication (approximately 105 days) INCLUSION CRITERIA: 1. All genders = 18 years of age, who fit one of the following criteria: Women of childbearing potential who are willing and able to use contraception from a minimum of 28 days before receipt of the first dose of study medication until completion of the final follow up visit. Women of non‐childbearing potential defined as being amenorrhoeic for >12 months with an appropriate clinical profile (e.g. age appropriate, menopausal symptoms). However, if indicated, this should be confirmed by follicle‐stimulating hormone levels consistent with menopause (according to local laboratory ranges). Alternatively, women without a uterus or who have been permanently sterilised (e.g. hysterectomy, bilateral salpingectomy or bilateral oophorectomy, but not tubal ligation). Men who are willing and able to use one of the contraception methods from the time of the first dose, until completion of the final follow up visit 2. Have a confirmed diagnosis of CF [positive sweat chloride v