Miglustat / OGT 918 in the Treatment of Cystic Fibrosis

Single Center, Double-blind, Randomized, Placebo-controlled, 2-period/2-treatment Crossover Study Investigating the Effect of Miglustat on the Nasal Potential Difference in Patients With Cystic Fibrosis Homozygous for the ΔF508 Mutation

Cystic fibrosis is a genetic disease caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR). The purpose of the study is to investigate the effects of miglustat on CFTR function in cystic fibrosis patients.

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: placebo; Drug: miglustat

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Corporacio Parc Tauli / Parc Tauli Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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: only women who are surgically sterile, who are in the menopause (no menstruation for at least one year) or those of childbearing potential who are using 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.

For children, a reliable method of contraception must be considered, if appropriate.

• Accepting for the duration of the study and for 3 months thereafter to use a condom and not to procreate a child (males only)
• Cystic fibrosis patients homozygous for the ΔF508 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 who will not undergo a pregnancy test prior to enrollment in the study
• History of significant lactose intolerance
• History of neuropathy
• History of cataracts or known increased risk of cataract formation
• Presence of clinically significant diarrhea (>3 liquid stolls per days for >7 days) without definable cause within 1 month prior to screening
• Any known factor of disease that might interfere with treatment compliance, study conduct or interruption of the results such as drug or alcohol dependence or psychiatric disease
• FEVI <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 investigational drug or therapy (e.g., gene therapy) within 1 month prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Oral miglustat capsules 200 mg t.i.d. for 1 week and a single 200 mg dose on day 8	Drug: miglustat; Other Names: Zavesca; OGT 918; 1.5- (Butylimino) -1.5- Dideoxy-D-Glucitol
Placebo Comparator: B; Oral placebo capsules matching in appearance miglustat capsules given t.i.d. for 1 week and a single dose on day 8	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in nasal potential difference (NPD) in response to isoproterenol in chloride-free buffer in the presence of amiloride	Baseline (pre-dose on day 1) to end-of-treatment (day 8)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in baseline NPD response	Baseline to end-of-treatment

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Paul van Giersbergen, PhD, Actelion; Principal Investigator: Christian Domingo-Ribas, MD, Corporacio Parc Tauli

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: September 28, 2007
• First Submitted That Met QC Criteria: September 28, 2007
• First Posted (Estimate): October 1, 2007

Study Record Updates

• Last Update Posted (Estimate): February 12, 2010
• Last Update Submitted That Met QC Criteria: February 11, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: cystic fibrosis; miglustat; nasal potential difference; Zavesca; Actelion; transmembrane conductance regulator (CFTR)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Glycoside Hydrolase Inhibitors; Miglustat
• Other Study ID Numbers: AC-056-201