NCT01025713撤回1 期
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS 9411 in Subjects With Cystic Fibrosis (CF)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability of escalating doses of inhaled GS-9411 in subjects with CF.
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of GS-9411 in patients with Cystic Fibrosis. GS-9411 is a sodium channel inhibitor, that may restore airway hydration and mucociliary clearance in the lung.
详细描述
GS-9411 is being evaluated as a potential therapy to improve airway hydration and mucociliary clearance in patients with cystic fibrosis. This study is evaluating the safety and tolerability of 2 dose levels of GS-9411 as an inhaled product, compared to a matched placebo.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females aged 18 to 65 years
- •Patients with diagnosis of CF as confirmed by at least one of the following:
- •Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR
- •Documented sweat sodium test ≥ 60 mmol/L OR
- •Abnormal nasal potential difference test OR
- •At least one well-characterized disease-causing genetic mutation in the CF transmembrane conductance regulatory (CFTR) gene AND
- •Accompanying symptoms characteristic of CF
- •Normal (or abnormal but not clinically significant) electrocardiogram (ECG)
- •Normal intraocular pressure (IOP) between 10 and 21 mm Hg at Screening.
- •Normal (or abnormal but not clinically significant) blood pressure (BP) and heart rate (HR) in the absence of any medications for hypertension; these will be measured after the subject has rested supine for 3 minutes; normal BP is taken to be 90 to 140 mm Hg systolic and 50 to 89 mm Hg diastolic; normal HR is taken to be 40 to 100 beats per minute (bpm)
- •Able to communicate well with the investigator and to comply with the requirements of the entire study
- •Provision of written informed consent to participate as shown by a signature on the volunteer consent form
- •Nonsmokers for at least 180 days (6 months) prior to Screening
- •Must be willing to abstain from alcohol and strenuous exercise during the 48 hours prior to Screening, 72 hours prior to initial dosing, and during the study
- •Forced expiratory volume in 1 second (FEV1) ≥ 50% predicted normal for age, gender, and height at Screening as per Knudson et al
- •Stable regimen of oral CF medications, dornase alfa, and physiotherapies for the period 28 days prior to Screening; those subjects taking continuous (non-cycling) inhaled antibiotics for prophylaxis must be on a stable regimen of these drugs for at least 90 days prior to Screening
- •Subjects must be in the off-phase of any cyclical inhaled antibiotic treatment regimen
- •Must test negative for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) at Screening
- •Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom) during heterosexual intercourse from Day -1 through completion of the study and continuing for at least 90 days from date of last dose of study drug
- •Male subjects must refrain from sperm donation from Day -1 through completion of the study and continuing for at least 90 days from the date of last dose of study drug
- •Nonlactating females. Females on hormone replacement therapy (estrogen/progesterone) or contraceptive therapy must be stabilized on a product and dose for at least 90 days prior to Screening
- •Females must have a negative serum gonadotropin pregnancy test at Screening and Day -1
- •Nonpregnant females of childbearing potential must agree to use highly effective (<1% failure rate) contraception during heterosexual intercourse from Screening, throughout the study, and for at least 30 days following the last dose of study drug
- •Glomerular filtration rate (GFR) of < 60 mL/min/1.73m2 at Screening (GFR to be calculated using the Cockcroft-Gault equation), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3× upper limits of normal (ULN)
- •Chest radiograph at Screening without significant acute findings (e.g., infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax); or chest radiograph, CT, or MRI obtained within the 90 days prior to Screening without acute findings or significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or atelectasis) are allowed. A chest radiograph obtained and interpreted between Screening and Day 1 is also acceptable for determining eligibility.
排除标准
- •Administration of any investigational drug or device in the 28 days prior to Screening
- •A need for any new medication during the period 28 days before first dosing with study drug, except those deemed by the principal investigator/clinical investigator not to interfere with the outcome of the study
- •Subjects who routinely use inhaled hypertonic saline must discontinue use for at least 14 days prior to clinic admission and for the duration of the study
- •Use of trimethoprim or high dose ibuprofen (> 800 mg/day) during the 28 days prior to first dosing
- •Serious adverse reaction or hypersensitivity to any drug
- •Existence of any surgical or medical condition which, in the judgment of the clinical investigator, might interfere with the absorption, distribution, metabolism, or excretion of the drug
- •Lactating females
- •History of airway intolerance to hypertonic saline
- •History of lung transplantation
- •History of a positive test for Burkholderia cepacia
- •History of cirrhosis or ascites
- •History of clinically significant adrenal disease
- •History of congestive heart failure diagnosed clinically or with documented left ventricular ejection fraction (LVEF) ≤ 40%
- •History of glaucoma
- •Consumption of drugs and/or herbal preparations capable of inducing hepatic enzyme metabolism (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John's Wort) within 28 days (or 5 half-lives of inducing agent, whichever is longer) of Screening
- •Subjects requiring any of the following drugs in the 28 days prior to Screening: diuretics (e.g., spironolactone, amiloride, thiazide), ACE inhibitors, angiotensin receptor blockers, oral corticosteroids, or medicines for hypertension
- •Donation or loss of greater than 400 mL of blood in the period 90 days (3 months) prior to Screening
- •Major surgery within 180 days (6 months) of Screening
- •Hemoglobin levels < 120 g/L in females or < 130 g/L in males taken at Screening and at Day -1
- •Serum potassium > 5 mEq/L taken at Screening and at Day -1
- •Poor venous access
研究组 & 干预措施
1
Experimental
GS-9411 2.4 mg
干预措施: GS-9411 (Drug)
2
Experimental
GS-9411 4.8 mg
干预措施: GS-9411 (Drug)
Placebo
Placebo Comparator
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of escalating doses of inhaled GS-9411 in subjects with CF.
时间窗: 5 Days
次要结局
- To assess the pharmacokinetics (PK) of GS-9411 and its metabolites, in plasma, urine, and sputum after single inhaled doses.(5 Days)
研究者
研究点 (1)
Loading locations...
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