NCT02325362已完成2 期
Single Center, Double-blind, Randomized, Placebo-controlled, Two-period/Two-treatment Crossover, Proof-of-mechanism Study Investigating the Effect of Miglustat on the Nasal Potential Difference in Adult Patients With Cystic Fibrosis Homozygous for the F508del Mutation
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Mean TCS in mV
研究概览
简要总结
The purpose of this study is to demonstrate that Miglustat restores the function of the cystic fibrosis transmembrane conductance regulator (CFTR) in adult patients with cystic fibrosis homozygous for the F508del mutation.
详细描述
The aims of this study are:
- To determine whether Miglustat can restore the function of the CFTR protein in adult patients with cystic fibrosis homozygous for the F508del mutation
- To evaluate the safety, tolerability and pharmacokinetics of Miglustat in adult patients with cystic fibrosis homozygous for the F508del mutation.
- To investigate pharmacokinetic-pharmacodynamic of Miglustat in adult patients with cystic fibrosis homozygous for the F508del mutation.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Inclusion criteria at screening visit (Visit 1):
- •Aged 18 years and older
- •Male or female
- •Women of childbearing potential must:
- •have a negative serum pregnancy test at Visit 1
- •agree to use from Visit 1 until 3 months after the last study drug intake a reliable method of contraception
- •Male patients accepting for the duration of the study and for 3 months thereafter to use a condom
- •Homozygous for the F508del mutation as confirmed by genetic testing
- •Sweat chloride ≥ 60 mmol/L
- •Basal nasal potential difference (NPD) ≤ -30.0 mV (equal to or more electrically negative than -30.0 mV) and total chloride secretion (TCS) ≥ - 5.0 mV for at least one nostril. However, if it is possible to analyze both nostrils, the total chloride secretion (TCS) is to be ≥ - 5.0 mV (equal to or more electrically positive than - 5.0 mV) in both nostrils.
- •FEV1 ≥ 25% of predicted
- •Able to comply with all protocol requirements
- •Signed informed consent prior to any study-mandated procedure
- •Inclusion criteria at randomization visit (Visit 2):
- •Women of child-bearing potential must have a negative urine pregnancy test
- •Basal nasal potential difference (NPD) ≤ - 30.0 mV (equal to or more electrically negative than - 30.0 mV) and total chloride secretion (TCS) ≥ - 5.0 mV for at least one nostril. However, if it is possible to analyze both nostrils, the total chloride secretion (TCS) is to be ≥ - 5.0 mV (equal to or more electrically positive than - 5.0 mV) in both nostrils.
排除标准
- •Any condition prohibiting the correct measurement of the NPD such as upper respiratory tract infection
- •Acute upper or lower respiratory tract infection requiring antibiotic intervention within 2 weeks of screening
- •Lung transplant recipient or patient on a lung transplant waiting list
- •Any modification in regular treatments (new treatment initiated or discontinued treatment) or modification in dosing within 2 weeks prior to start of Period 1
- •Moderate/Severe renal impairment (creatinine clearance < 70 mL/min as per Cockroft and Gault)
- •Systemic corticosteroids (> 10 mg/day prednisone or equivalent) within 14 days prior to screening and up to start of study
- •Women who are breast-feeding, pregnant, or who plan to become pregnant during the course of the study
- •History of significant lactose intolerance
- •Presence of clinically significant diarrhoea (> 3 liquid stools per day for > 7 days) without definable cause within one month prior to screening
- •Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
- •Active or passive smoking
- •Hypersensitivity to Miglustat or any excipients
- •Planned treatment or treatment with another investigational drug or therapy (e.g., gene therapy) within one month prior to randomization
- •Known concomitant life-threatening disease with a life expectancy < 12 months
- •Indication against Isuprel® (Isoproterenol) including heart diseases.
研究组 & 干预措施
Miglustat then placebo
Experimental
10 patients will received Miglustat then the placebo
干预措施: Miglustat ; placebo (Drug)
Placebo then Miglustat
Experimental
10 patients will received Placebo then Miglustat
干预措施: Placebo ; Miglustat (Drug)
结局指标
主要结局
Mean TCS in mV
时间窗: Day 14
TCS (Total Chloride Secretion) is the sum of responses in nasal potential difference (NPD) calculated as the mean of the right and left nostril measurements for each patient
次要结局
- Change in electrochemical skin conductance(day 14)
- TCS difference in mV(Day 14)
- Percentage of patients with a TCS at end-of-treatment ≤ - 5 mV(day 14)
- Change of basal NPD in mV(day 14)
- FEV1 (in % of predicted)(day 14)
- Number of cells expressing CFTR at the cell membrane (in %percentage)(day 14)
- Percentage of patients with a TCS response to treatment ≤ - 5 mV(day 14)
- Wilschanski's index change(day 14)
- Change of the response in NPD after superfusion with amiloride(day 14)
- Change of the response in NPD after superfusion with a chloride-free buffer in the presence of amiloride(day 14)
- Sweat chloride concentration in mmol/L(day 14)
研究者
研究点 (1)
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