"Estudio unicéntrico, a doble ciego, aleatorizado y controlado con placebo, cruzado de 2 brazos, para investigar el efecto de miglustat sobre la diferencia de potencial nasal en pacientes con fibrosis quística homocigotos para la mutación ?F508"

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2006-002049-35-ES
• Date of registration: 28/05/2007
• Prospective Registration: Yes
• Primary sponsor: Actelion Pharmaceuticals Ltd
• Public title: "Estudio unicéntrico, a doble ciego, aleatorizado y controlado con placebo, cruzado de 2 brazos, para investigar el efecto de miglustat sobre la diferencia de potencial nasal en pacientes con fibrosis quística homocigotos para la mutación ?F508"
• Scientific title: "Estudio unicéntrico, a doble ciego, aleatorizado y controlado con placebo, cruzado de 2 brazos, para investigar el efecto de miglustat sobre la diferencia de potencial nasal en pacientes con fibrosis quística homocigotos para la mutación ?F508"
• Date of first enrolment: 22/07/2007
• Target sample size: 25
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002049-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: yes; Other: yes; Other trial design description: 2-period/2-treatment crossover, proof-of-concept; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Key inclusion & exclusion 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:
Ø barrier type devices (e.g., female condom, diaphragm and contraceptive sponge) used ONLY in combination with a spermicide
Ø intrauterine devices
Ø oral contraceptive agent
Ø Depo-Provera TM (medroxyprogesterone acetate)
Ø 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 ?F508 mutation as confirmed by genetic test

· Signed informed consent prior to any study-mandated procedure.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 into 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 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 investigational drug or therapy (e.g., gene therapy) within 1 month prior to randomization


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

fibrosis quística
MedDRA version: 8.1 Level: LLT Classification code 10011762 Term: Cystic fibrosis

Intervention(s)

Trade Name: Zavesca
Product Name: miglustat
Product Code: OGT 918
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Miglustat
CAS Number: 72599-27-0
Current Sponsor code: OGT 918
Other descriptive name: 1,5 (Butylimino)-1,5-dideoxy-D-glucitol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To demonstrate that miglustat restores the function of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients with cystic fibrosis homozygous for the ?F508 mutation as reflected in nasal potential difference (NPD).

Primary end point(s): Primary endpoint:

Change from baseline (pre-dose on day 1) to end-of-treatment (day 8) in nasal potential difference (NPD) in response to isoproterenol in chloride-free buffer in the presence of amiloride
Assumptions:
· A difference of 3.2 mV to the isoproterenol challenge between placebo and miglustat treatment (as measured after the morning dose on day 8 of each period) represents about 20% of the response seen in non cystic fibrosis subjects, which is considered clinically significant.
· No carry-over effect is expected with a washout of 2 weeks.
· No period effect is expected
· It is assumed that the NPD is normally distributed and that the standard deviation of the difference of 2 repeat measurements is 4.4 mV.

Secondary endpoints:
· Change from baseline to end-of-treatment in baseline NPD response
· Change from baseline to end-of-treatment in amiloride-sensitive NP
· Change from baseline to end-of-treatment in low-chloride sensitive NPD in the presence of amiloride
· Change from baseline to end-of-treatment in ATP-sensitive NPD in the presence of chloride-free buffer, amiloride, and isoproterenol
· Change from baseline to end-of-treatment in sweat sodium and chloride concentration

Baseline and end-of-treatment are defined as predose on day 1 and 8, respectively, of both treatment periods

Secondary Objective: . To investigate the effect of miglustat on the concentration of sodium and chloride in sweat in this patient population.

· To investigate the safety and tolerability of miglustat in this patient population.

Secondary ID(s)

AC-056-201

Ethics review

Status: Approved
Approval date: 12/07/2007
Contact:

Results

• Results available: Yes
• Date Posted: 06/08/2015
• Date Completed: 22/02/2008
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-002049-35/results