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

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.