A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study Investigating the Optimal Dose Regimen, Efficacy, and Safety of Adding Oral Cysteamine in Adult Patients Being Treated for an Exacerbation of CF-associated Lung Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 17
- 主要终点
- Change From Baseline in Sputum Bacterial Load
研究概览
简要总结
This study investigates the use of cysteamine in the treatment of adults with Cystic Fibrosis who are experiencing an exacerbation of CF-associated lung disease. There are six different potential dosing regimens, including one that is placebo.
详细描述
This is a multicenter, double-blind, randomized, placebo-controlled, 6-arm study to investigate the optimal dose regimen, efficacy, and safety of cysteamine in the treatment of adult patients with CF who are experiencing an exacerbation of CF-associated lung disease. Patients will be screened for the study and eligible patients will be randomized to receive either cysteamine or placebo as add-on therapy to their standard of care treatment for CF-associated lung disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CF-associated lung disease with documented history of chronic infection with Gram-negative organism(s)
- •Established patient of the Principal Investigator's CF Multi Disciplinary Team (MDT)
- •Age ≥18 years
- •Weight >40 kg
- •FEV1 >30% of predicted within the 6 months prior to study exacerbation
- •At the baseline visit: experiencing a new exacerbation of CF-associated lung disease (based on Investigator assessment of ≥4 symptoms present on the Fuchs' criteria) requiring treatment that includes an aminoglycoside antibiotic
- •Females of childbearing potential will be included if they are either sexually inactive (sexually abstinent for 14 days prior to the first study drug dose continuing through 28 days after the last study drug dose, or using one of the following highly effective contraceptive (i.e. results in <1% failure rate when used consistently and correctly) methods in this trial:
- •intrauterine device (IUD);
- •surgical sterilization of the partner (vasectomy for 6 months minimum);
- •combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal);
- •progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable);
- •intrauterine hormone releasing system (IUS);
- •bilateral tubal occlusion.
- •Females of childbearing potential agree to remain sexually inactive or to keep the same birth control method for at least 28 days following the last dose.
- •A female of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first study drug dose:
- •hysteroscopic sterilization;
- •bilateral tubal ligation or bilateral salpingectomy;
- •hysterectomy;
- •bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to the first study drug dose and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status.
- •A non-vasectomized male subject agrees to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study medication and the female partner agrees to comply with inclusion 7 or
- •For a vasectomized male who has had his vasectomy 6 months or more prior to study start, it is required that they use a condom during sexual intercourse. A male who has been vasectomized less than 6 months prior to study start must follow the same restrictions as a non-vasectomized male.
- •If male, agrees not to donate sperm from the first study drug dose until 90 days after dosing.
- •Willing and able to comply with all protocol requirements and procedures, including induction of sputum, if necessary
- •Willing and able to provide signed and dated informed consent
排除标准
- •Hypersensitive to cysteamine or to any of the excipients
- •Hypersensitive to penicillamine
- •Transplant recipient
- •Participation in any other interventional clinical research study (participation in observational studies is not exclusionary) within 30 days of Baseline (Day 0), and any planned participation in an interventional clinical research study for the duration of this study
- •If female, pregnancy, planned pregnancy, or breast-feeding
- •Any other significant disease/disorder which, in the Investigator's opinion, either puts the patient at risk due to study participation, or may influence the results of the study or the patient's ability to participate in the study
研究组 & 干预措施
High Dose, Once per day
Patient takes one oral dose of Cysteamine (high dose) per day, in the morning. The patient takes two oral placebo doses, one at mid-day and one in the evening.
干预措施: Placebo Oral Capsule (Drug)
High Dose, Once per day
Patient takes one oral dose of Cysteamine (high dose) per day, in the morning. The patient takes two oral placebo doses, one at mid-day and one in the evening.
干预措施: Cysteamine (Drug)
High Dose, Twice per day
Patient takes two oral doses of Cysteamine (high dose) per day, one in the morning and one in the evening. The patient takes one oral placebo dose, at mid-day.
干预措施: Cysteamine (Drug)
High Dose, Twice per day
Patient takes two oral doses of Cysteamine (high dose) per day, one in the morning and one in the evening. The patient takes one oral placebo dose, at mid-day.
干预措施: Placebo Oral Capsule (Drug)
High Dose, Three times per day
Patient takes three oral doses of Cysteamine (high dose) per day, one in the morning, one at mid-day and one in the evening.
干预措施: Cysteamine (Drug)
Placebo
Patient takes three oral doses of placebo, one in the morning, one at mid-day and one in the evening.
干预措施: Placebo Oral Capsule (Drug)
Low Dose, Three times per day
Patient takes three oral doses of Cysteamine (low dose) per day, one in the morning, one at mid-day and one in the evening.
干预措施: Cysteamine (Drug)
Low Dose, Three times per day
Patient takes three oral doses of Cysteamine (low dose) per day, one in the morning, one at mid-day and one in the evening.
干预措施: Placebo Oral Capsule (Drug)
Mid-Range Dose, Three times per day
Patient takes three oral doses of Cysteamine (mid-range dose) per day, one in the morning, one at mid-day and one in the evening.
干预措施: Cysteamine (Drug)
Mid-Range Dose, Three times per day
Patient takes three oral doses of Cysteamine (mid-range dose) per day, one in the morning, one at mid-day and one in the evening.
干预措施: Placebo Oral Capsule (Drug)
结局指标
主要结局
Change From Baseline in Sputum Bacterial Load
时间窗: Baseline through Day 21/End of Study
Change from baseline through to Day 21 in log10 cfu/ml transformed total gram negative sputum bacterial load
Safety and Tolerability Assessed by the Number of Subjects With Adverse Events
时间窗: Baseline through Day 21/End of Study
Assessed by variables such as adverse events (AEs), laboratory assessments, physical examinations, and vital signs.
次要结局
- Change From Baseline in C-Reactive Protein(Baseline through Day 21)
- Assessment of Sputum Cysteamine Levels(Day 14)
- Change From Baseline in CFRSD-CRISS(Baseline through to Day 21)
- Change From Baseline in CFQ-R(Baseline through Day 21/End of Study)
- Change From Baseline in Neutrophil Elastase Levels(Baseline through Day 21/End of Study)
- Change From Baseline in Sputum IL8(Baseline through Day 21/End of Study)
- Change From Baseline in FEV1(Baseline through Day 21/End of Study)
- Change From Baseline in BMI(Baseline through Day 21/End of Study)
- Change From Baseline in Jarad and Sequeiros Symptom Score Questionnaire(changes from baseline at day 7 and day 14)
- Change From Baseline in Weight(Baseline through Day 21/End of Study)
- Change From Baseline in Blood Leukocyte Count(Baseline through Day 21/End of Study)
- Assessment of Blood Cysteamine Levels(Day 14)