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

NCT02325362 | Completed Phase 2

• 2 other identifiers: P1207032013-000497-29
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

Cystic fibrosis; CFTR; F508del mutation; Miglustat; Total Chloride Secretion; Nasal Potential Difference

Outcome Measures

Primary Outcomes (2)

• Mean TCS in mV

  TCS (Total Chloride Secretion) is the sum of responses in nasal potential difference (NPD) calculated as the mean of the right and left nostril measurements for each patient

  day 1

• Mean TCS in mV

  TCS (Total Chloride Secretion) is the sum of responses in nasal potential difference (NPD) calculated as the mean of the right and left nostril measurements for each patient

  Day 14

Secondary Outcomes (21)

• TCS difference in mV

  day 1

• TCS difference in mV

  Day 14

• Percentage of patients with a TCS response to treatment ≤ - 5 mV

  day 1

• Percentage of patients with a TCS response to treatment ≤ - 5 mV

  day 14

• Percentage of patients with a TCS at end-of-treatment ≤ - 5 mV

  day 1

Study Arms (2)

Miglustat then placebo

EXPERIMENTAL

10 patients will received Miglustat then the placebo

Drug: Miglustat ; placebo

Placebo then Miglustat

EXPERIMENTAL

10 patients will received Placebo then Miglustat

Drug: Placebo ; Miglustat

Interventions

Miglustat ; placebo 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.

Miglustat then placebo

Placebo ; Miglustat 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.

Placebo then Miglustat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Actelion: collaborator
• CRCM (Centres de Ressources et de Compétences de la Mucoviscidose): collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Assistance publique-Hôpitaux de Paris, Hôpital Cochin

Paris, 75014, France

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

miglustat

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Isabelle FAJAC, MD, PhD.

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2014
• First Posted: December 25, 2014
• Study Start: March 17, 2015
• Primary Completion: April 3, 2017
• Study Completion: April 3, 2017
• Last Updated: November 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)