A Randomised, Double-Blind, Placebo Controlled, Two-Part Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Repeat Dose of Inhaled ETD001 in People With Cystic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 21
- 主要终点
- Part A: Safety and tolerability of repeat inhaled doses of ETD001 monitored by assessment of adverse events
研究概览
简要总结
This study is the first to give ETD001 to people with CF. The study will be run in two parts. Part A will assess if ETD001 is safe to give to people with CF, and Part B will assess if ETD001 improves lung function. The study drug is taken twice a day, in Part A it is taken for 7 days and in Part B for 28 days. In Part B there will be a separate period where dummy medicine is given for 28 days so the treatments can be compared.
In Part A participants will receive 13 doses of either ETD001 or placebo, 8 people will take part. Participants will take up to 56 days to finish the study and make 5 outpatient visits.
In Part B participants will receive 55 doses of ETD001 and 55 doses of placebo, 32 people will take part. Participants will take up to 140 days to finish the study and will make 8 outpatient visits.
Study assessments include physical examinations, vital signs, heart traces, blood/urine samples, breathing tests and health questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male & female ≥ 18 years of age, who fit one of the following criteria:
- •Women of childbearing potential using permitted contraception a minimum of 28 days before dosing until completion of the final follow up visit; Women of non-childbearing potential; Men using contraception from the time of the first dose, until completion of the final follow up visit;
- •Confirmed diagnosis of CF
- •FEV1 ≥ 40% and ≤ 90% of predicted normal for age, gender, and height
- •Able to reproducibly perform spirometry manoeuvres
- •Clinically stable CF lung disease
- •Routine CF therapy has not changed within 28 days prior to screening.
- •Provided written informed consent.
- •Body mass index (BMI) > 16 and < 30 kg/m2
排除标准
- •Abnormal liver function
- •Abnormal renal function
- •History of solid organ transplant
- •Chest x-ray within the past 12 months with abnormalities suggesting unstable pulmonary disease other than CF
- •Received CFTR modulator therapy in the 60 days before screening
- •Changes in bronchodilator, corticosteroid or other anti-inflammatory medications 14 days before screening
- •Unable to withhold use of long-acting bronchodilators 24 hours or short-acting bronchodilators 6 hours before spirometry assessments
- •Unable to withhold use of anti-cholinergics within 24 hours of spirometry
- •Started dornase alfa, hypertonic saline, or other airway clearing therapy less than 28 days before screening
- •Using inhaled antibiotics for less than 2 complete cycles and unable to complete the entire study during the off or on cycle.
- •Changes in inhaled or oral antibiotic use within 14 days of screening
- •Taking oral corticosteroids in excess of 10 mg/day or 20 mg every other day within 14 days of screening
- •Use of diuretics, or renin-angiotensin aldosterone system antihypertensive drugs , drospirenone, or trimethoprim in the 28 days before screening
- •Presence of co-morbidities and medical history in the opinion of the investigator, may pose additional risk by participating in the study, or may confound the results of the study
研究组 & 干预措施
Part A - 7 day treatment period - parallel group
Twice daily doses of ETD001/placebo for 6 days, single dose on Day 7
干预措施: ETD001 (Drug)
Part A - 7 day treatment period - parallel group
Twice daily doses of ETD001/placebo for 6 days, single dose on Day 7
干预措施: Placebo (Drug)
Part B - 2 x 28 day treatment period - crossover
Two treatment periods of twice daily doses of ETD001/placebo for 27 days, single dose on Day 28 separated by a period of 28 days
干预措施: ETD001 (Drug)
Part B - 2 x 28 day treatment period - crossover
Two treatment periods of twice daily doses of ETD001/placebo for 27 days, single dose on Day 28 separated by a period of 28 days
干预措施: Placebo (Drug)
结局指标
主要结局
Part A: Safety and tolerability of repeat inhaled doses of ETD001 monitored by assessment of adverse events
时间窗: 28 days
Incidence of treatment emergent adverse events(AE)/serious AE), withdrawals due to AE
Part B: Effect of repeat inhaled doses of ETD001 on percent predicted forced expiratory volume in 1 second (ppFEV1)
时间窗: Treatment Period 1 & 2 - Day 1 (pre-dose, 1, 2 & 4 hours post dose), Day 14 (pre-dose, 1 & 2 hours post), Day 28 (at 0, 1, 2 & 4 hours post dose)
Change in ppFEV1 measured by spirometry from baseline to Day 28 (for either Treatment Period 1 or Treatment Period 2), compared to placebo
次要结局
- Part B: Characterisation of plasma PK(Treatment Period 1 & 2; Day 1 (0 & 1 hour), Day 14 (0 & 2 hours), Day 28 (0 & 4 hours), Follow up (Day 105) 1 sample)
- Part A: Characterisation of plasma pharmacokinetics (PK)(Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours, Day 7 (pre-dose), Day 28 (single sample))
- Part B: Effect of repeat inhaled doses of ETD001 on other lung function assessments(Treatment Period 1 & 2; Day 1 (pre-dose, 1, 2 & 4 hours), Day 14 (pre-dose, 1 & 2 hours), Day 28 (pre-dose, 1, 2 & 4 hours))
- Part B: Safety and tolerability of repeat inhaled doses of ETD001 monitored by assessment of adverse events(105 days)
- Part B: Effect of repeat inhaled doses of ETD001 on the quality of life questionnaire, the Cystic Fibrosis Questionnaire (revised) (CFQ-R)(Treatment Period 1 & 2; Day 1 & Day 28 (pre-dose))
- Part A: Characterisation of urine PK(Day 1 (0 - 6 hours))