Miglustat in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

Single Center, Double-blind, Randomized, Placebo-controlled, Two-period/Two-treatment Crossover Study Investigating the Effect of Miglustat on the Nasal Potential Difference in Patients With Cystic Fibrosis Homozygous for the F508del Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00742092
• Other study ID #: AC-056A202
• Status: Completed
• Phase: Phase 2
• First received: August 26, 2008
• Last updated: March 5, 2014
• Start date: August 2008
• Est. completion date: December 2008

Study information

• Verified date: March 2014
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Institutional Review BoardBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentBelgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial Summary

Single Center, Double-Blind, Randomized, Placebo-Controlled, Two-Period/Two-Treatment Crossover Study Investigating the Effect of Miglustat on the Nasal Potential Difference in Patients With Cystic Fibrosis Homozygous for the F508del Mutation

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

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. Women of childbearing potential must use 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. A woman is considered to have child-bearing potential unless she meets at least one of the following criteria:

• 6 weeks post-surgical bilateral salpingo-oophorectomy or hysterectomy

• Premature ovarian failure confirmed by a specialist gynecologist

• Age > 50 years and not treated with any kind of HRT for at least 2 years prior to screening, and with amenorrhea for at least 24 consecutive months prior to screening and a serum FSH level of > 40 IU/L at screening.

• Age > 55 years and treated with HRT prior to screening with an appropriate medical documentation of spontaneous amenorrhea for at least 24 months. For female patients in the pediatric age range, a reliable method of contraception must be considered, if appropriate.

• Male patients accepting for the duration of the study and for 3 months thereafter to use a condom and not to procreate a child (not in case of azoospermia)

• Cystic fibrosis patients homozygous for the F508del 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 of childbearing potential who will not undergo a pregnancy test prior to enrollment into the study

• History of significant lactose intolerance

• History of neuropathy

• Presence of clinically significant diarrhea (> 3 liquid stools per day for > 7 days) without definable cause within 1 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

• FEV1 < 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 investigationaldrug or therapy (e.g., gene therapy) within 1 month prior to randomization

• Breast-feeding, pregnant women or women who plan to become pregnant during the course of the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• miglustat
Oral miglustat capsules 200 mg t.i.d. (three times a day) for 7 days and a single 200 mg dose on Day 8
• placebo
Oral placebo capsules matching in appearance miglustat capsules given t.i.d. (three times a day) for 7 days and a single dose on Day 8

Locations

Country	Name	City	State
Belgium	Universite Catholique de Louvain	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The sum of responses in nasal potential difference (NPD) after perfusion with isoproterenol and chloride-free buffer (TCS: Total Chloride Secretion), in the presence of amiloride.		Change from baseline (pre-dose on Day 1) to end-of-treatment (Day 8)	No
Secondary	Change in basline nasal potential difference (NPD) response		From baseline (pre-dose on Day 1) to end-of-treatment	No