Miglustat in Cystic Fibrosis
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
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.