Effect of Miglustat on the Nasal Potential Difference in Patients With Cystic Fibrosis Homozygous for the F508del Mutation

The aims of this study are:

• To determine whether Miglustat can restore the function of the CFTR protein in adult patients with cystic fibrosis homozygous for the F508del mutation
• To evaluate the safety, tolerability and pharmacokinetics of Miglustat in adult patients with cystic fibrosis homozygous for the F508del mutation.
• To investigate pharmacokinetic-pharmacodynamic of Miglustat in adult patients with cystic fibrosis homozygous for the F508del mutation.

Inclusion criteria

Inclusion criteria

at screening visit (Visit 1):

• Aged 18 years and older
• Male or female
• Women of childbearing potential must:

• have a negative serum pregnancy test at Visit 1
• agree to use from Visit 1 until 3 months after the last study drug intake a reliable method of contraception
• Male patients accepting for the duration of the study and for 3 months thereafter to use a condom
• Homozygous for the F508del mutation as confirmed by genetic testing
• Sweat chloride ≥ 60 mmol/L
• Basal nasal potential difference (NPD) ≤ -30.0 mV (equal to or more electrically negative than -30.0 mV) and total chloride secretion (TCS) ≥ - 5.0 mV for at least one nostril. However, if it is possible to analyze both nostrils, the total chloride secretion (TCS) is to be ≥ - 5.0 mV (equal to or more electrically positive than - 5.0 mV) in both nostrils.
• FEV1 ≥ 25% of predicted
• Able to comply with all protocol requirements
• Signed informed consent prior to any study-mandated procedure

Inclusion criteria

at randomization visit (Visit 2):

• Women of child-bearing potential must have a negative urine pregnancy test
• Basal nasal potential difference (NPD) ≤ - 30.0 mV (equal to or more electrically negative than - 30.0 mV) and total chloride secretion (TCS) ≥ - 5.0 mV for at least one nostril. However, if it is possible to analyze both nostrils, the total chloride secretion (TCS) is to be ≥ - 5.0 mV (equal to or more electrically positive than - 5.0 mV) in both nostrils.

Exclusion criteria

• Any condition prohibiting the correct measurement of the NPD such as upper respiratory tract infection
• Acute upper or lower respiratory tract infection requiring antibiotic intervention within 2 weeks of screening
• Lung transplant recipient or patient on a lung transplant waiting list
• Any modification in regular treatments (new treatment initiated or discontinued treatment) or modification in dosing within 2 weeks prior to start of Period 1
• Moderate/Severe renal impairment (creatinine clearance < 70 mL/min as per Cockroft and Gault)
• Systemic corticosteroids (> 10 mg/day prednisone or equivalent) within 14 days prior to screening and up to start of study
• Women who are breast-feeding, pregnant, or who plan to become pregnant during the course of the study
• History of significant lactose intolerance
• Presence of clinically significant diarrhoea (> 3 liquid stools per day for > 7 days) without definable cause within one 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
• Active or passive smoking
• Hypersensitivity to Miglustat or any excipients
• Planned treatment or treatment with another investigational drug or therapy (e.g., gene therapy) within one month prior to randomization
• Known concomitant life-threatening disease with a life expectancy < 12 months
• Indication against Isuprel® (Isoproterenol) including heart diseases.