Miglustat in Cystic Fibrosis

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: miglustat
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>miglustat | Drug: miglustat<br>* Oral miglustat capsules 200 mg t.i.d. (three times a day) for 7 days and a single 200 mg dose on Day 8<br>|
| Placebo Comparator: 2<br>placebo | Drug: placebo<br>* Oral placebo capsules matching in appearance miglustat capsules given t.i.d. (three times a day) for 7 days and a single dose on Day 8<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The sum of responses in nasal potential difference (NPD) after perfusion with isoproterenol and chloride-free buffer (TCS: Total Chloride Secretion), in the presence of amiloride. |  | Change from baseline (pre-dose on Day 1) to end-of-treatment (Day 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in basline nasal potential difference (NPD) response |  | From baseline (pre-dose on Day 1) to end-of-treatment |