Single center, double-blind, randomized, placebo-controlled, two-period/two-treatment crossover study investigating the effect of miglustat on the nasal potential difference in patients with cystic fibrosis homozygous for the F508del mutatio

• Conditions: Cystic fibrosis homozygous for the F508del mutation; MedDRA version: 9.1Level: LLTClassification code 10011762Term: Cystic fibrosis

• Registration Number: EUCTR2008-002352-20-BE
• Lead Sponsor: Actelion Pharmaceuticals Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-17
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Aged 12 years and older
• Male or female
• Non-pregnant women who are to remain non-pregnant for 3 months after the end of the study. Women of childbearing potential must use a reliable method of contraception. Reliable methods of contraception for female patients include the following:
- barrier type devices (e.g., female condom, diaphragm and contraceptive sponge) used ONLY in combination with a spermicide
- intrauterine devices
- oral contraceptive agent
- Depo-Provera TM (medroxyprogesterone acetate)
- levonorgestrel implants
Abstention, the rhythm method or contraception by the partner alone are NOT reliable methods of contraception. A woman is considered to have child-bearing potential unless she meets at least one of the following criteria:
- 6 weeks post-surgical bilateral salpingo-oophorectomy or hysterectomy
- Premature ovarian failure confirmed by a specialist gynecologist
- Age > 50 years and not treated with any kind of HRT for at least 2 years prior to screening, and with amenorrhea for at least 24 consecutive months prior to screening and a serum FSH level of > 40 IU/L at screening.
- Age > 55 years and treated with HRT prior to screening with an appropriate medical documentation of spontaneous amenorrhea for at least 24 months.

For female patients in the pediatric age range, a reliable method of contraception must be considered, if appropriate.
• Male patients accepting for the duration of the study and for 3 months thereafter to use a condom and not to procreate a child (not in case of azoospermia)
• Cystic fibrosis patients homozygous for the F508del mutation as confirmed by genetic test
• Signed informed consent prior to any study-mandated procedure.

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Any condition prohibiting the correct measurement of the NPD such as upper respiratory tract infection
• Acute upper respiratory tract or pulmonary exacerbation requiring antibiotic intervention within 2 weeks of screening
• Severe renal impairment (creatinine clearance < 30 mL/min as per Cockroft and Gault)
• Female patients of childbearing potential who will not undergo a pregnancy test prior to enrollment into the study
• History of significant lactose intolerance
• History of neuropathy
• Presence of clinically significant diarrhea (> 3 liquid stools per day for > 7 days) without definable cause within 1 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
• FEV1 < 25% of predicted normal
• Oxygen saturation at rest < 88%
• Active or passive smoking as measured using the Smokelyzer®
• Hypersensitivity to miglustat or any excipients
• Planned treatment or treatment with another investigational drug or therapy (e.g., gene therapy) within 1 month prior to randomization
• Breast-feeding, pregnant women or women who plan to become pregnant during the course of the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that miglustat restores the function of the cystic fibrosis transmembrane conductance regulator (CFTR), as reflected in nasal potential difference (NPD), in patients with cystic fibrosis homozygous for the F508del mutation.;Secondary Objective: • To investigate the effect of miglustat on the concentration of sodium and chloride in sweat in this patient population.<br>• To investigate the safety and tolerability of miglustat in this patient population.<br>;Primary end point(s): The sum of responses in NPD after perfusion with isoproterenol and chloride-free buffer (TCS: Total Chloride Secretion), in the presence of amiloride will be measured. The primary endpoint is the change from baseline (pre-dose on Day 1) to end-of-treatment (Day 8)