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

NCT ID: NCT02325362

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-17
• Study Completion Date: 2017-04-03

Brief Summary

The purpose of this study is to demonstrate that Miglustat restores the function of the cystic fibrosis transmembrane conductance regulator (CFTR) in adult patients with cystic fibrosis homozygous for the F508del mutation.

Detailed Description

The aims of this study are:

1. To determine whether Miglustat can restore the function of the CFTR protein in adult patients with cystic fibrosis homozygous for the F508del mutation

2. To evaluate the safety, tolerability and pharmacokinetics of Miglustat in adult patients with cystic fibrosis homozygous for the F508del mutation.

3. To investigate pharmacokinetic-pharmacodynamic of Miglustat in adult patients with cystic fibrosis homozygous for the F508del mutation.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Miglustat then placebo

10 patients will received Miglustat then the placebo

Group Type: EXPERIMENTAL

Miglustat ; placebo

Intervention Type: DRUG

For this 2 x 2 (2 periods /2 treatments) crossover design each patient will receive Miglustat during the first period (2 weeks), following by a wash out period(14 days (up to 4 weeks)), then Placebo during the second period (2 weeks). 30 days follow-up will be carried out after end-of-treatment of the second period.

Placebo then Miglustat

10 patients will received Placebo then Miglustat

Group Type: EXPERIMENTAL

Placebo ; Miglustat

Intervention Type: DRUG

For this 2 x 2 (2 periods /2 treatments) crossover design each patient will receive Placebo during the first period (2 weeks), following by wash out period (14 days (up to 4 weeks)), then Miglustat during the second period (2 weeks). 30 days follow-up will be carried out after end of treatment of the second period.

Interventions

Miglustat ; placebo

For this 2 x 2 (2 periods /2 treatments) crossover design each patient will receive Miglustat during the first period (2 weeks), following by a wash out period(14 days (up to 4 weeks)), then Placebo during the second period (2 weeks). 30 days follow-up will be carried out after end-of-treatment of the second period.

Intervention Type: DRUG

Placebo ; Miglustat

For this 2 x 2 (2 periods /2 treatments) crossover design each patient will receive Placebo during the first period (2 weeks), following by wash out period (14 days (up to 4 weeks)), then Miglustat during the second period (2 weeks). 30 days follow-up will be carried out after end of treatment of the second period.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: collaborator

CRCM (Centres de Ressources et de Compétences de la Mucoviscidose)

UNKNOWN

Sponsor Role: collaborator

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Isabelle FAJAC, MD, PhD.

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Locations

Assistance publique-Hôpitaux de Paris, Hôpital Cochin

Paris, , France

Countries

France

Other Identifiers

2013-000497-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P120703

Identifier Type: -

Identifier Source: org_study_id