Miglustat / OGT 918 in the Treatment of Cystic Fibrosis

• ClinicalTrials.gov Identifier: NCT00537602
• Recruitment Status: Terminated
• First Posted: October 1, 2007
• Last Update Posted: February 12, 2010
• Sponsor: Actelion
• Information provided by: Actelion

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: miglustat; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: November 2007
• Actual Primary Completion Date: February 2008
• Actual Study Completion Date: March 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change in baseline NPD response [ Time Frame: Baseline to end-of-treatment ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Spain

Corporacio Parc Tauli / Parc Tauli Hospital

Barcelona, Spain

Sponsors and Collaborators

Actelion

Investigators

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

More Information

• Responsible Party: Paul van Giersbergen , PhD, Actelion
• ClinicalTrials.gov Identifier: NCT00537602
• Other Study ID Numbers: AC-056-201
• First Posted: October 1, 2007
• Last Update Posted: February 12, 2010
• Last Verified: February 2010

Keywords provided by Actelion:

cystic fibrosis; miglustat; Zavesca; Actelion; nasal potential difference; transmembrane conductance regulator (CFTR)

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Miglustat; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Physiological Effects of Drugs