Miglustat in Cystic Fibrosis

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 Mutation


Eligibility Criteria:
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™ (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

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 investigationaldrug 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.