Long Term Administration of Inhaled Mannitol in Cystic Fibrosis – A Safety and Efficacy Trial in Adult Cystic Fibrosis Subjects

• Register: EUCTR
• Last refreshed on: 22 May 2017
• Main ID: EUCTR2013-005357-79-BE
• Date of registration: 01/07/2014
• Prospective Registration: Yes
• Primary sponsor: Pharmaxis Limited
• Public title: Long Term Administration of Inhaled Mannitol in Cystic Fibrosis – A Safety and Efficacy Trial in Adult Cystic Fibrosis Subjects
• Scientific title: Long Term Administration of Inhaled Mannitol in Cystic Fibrosis – A Safety and Efficacy Trial in Adult Cystic Fibrosis Subjects
• Date of first enrolment: 20/08/2014
• Target sample size: 440
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005357-79
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Control is a subtherapeutic active, identical to the IMP except for amount of drug in each capsule. Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Bulgaria, Canada, Czech Republic, France, Greece, Hungary, Israel, Italy, Mexico, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Ukraine, United Kingdom, United States

Contacts

• Name: Lorena Figueroa
• Affiliation: Pharmaxis Limited

• Name: Lorena Figueroa
• Affiliation: Pharmaxis Limited

Key inclusion & exclusion criteria

Inclusion criteria:
The subject must meet all of the following criteria:
1. Have given written informed consent to participate in this trial in accordance with local regulations;
2. Have a confirmed diagnosis of cystic fibrosis (positive sweat chloride value = 60 mEq/L) and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype);
3. Be aged at least 18 years old;
4. Have FEV1 > 40 % and < 90% predicted (using NHanes III [1]);
5. Be able to perform all the techniques necessary to measure lung function;
6.Be adherent with maintenance therapies (antibiotics and or rhDNase), if used, for at least 80% of the time in the two weeks prior to visit 1 and
7. If rhDNase and/or maintenance antibiotic are being used treatment must have been established at least 1 month prior to screening (Visit 0). The subject should remain on the rhDNase and / or maintenance antibiotics for the duration of the trial. The subject should not commence treatment with rhDNase or maintenance antibiotics during the trial.

Are the trial subjects under 18? no
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 418
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion criteria:
The subject must NOT meet any of the following criteria:
1. Be investigators, site personnel directly affiliated with this trial, or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted;
2. Be considered “terminally ill” or eligible for lung transplantation;
3. Have had a lung transplant;
4. Be using maintenance nebulized hypertonic saline in the 2 weeks prior to visit 1;
5. Have had a significant episode of hemoptysis (> 60 mL) in the three months prior to Visit 0;
6. Have had a myocardial infarction in the three months prior to Visit 0;
7. Have had a cerebral vascular accident in the three months prior to Visit 0;
8. Have had major ocular surgery in the three months prior to Visit 0;
9. Have had major abdominal, chest or brain surgery in the three months prior to Visit 0;
10. Have a known cerebral, aortic or abdominal aneurysm;
11. Be breast feeding or pregnant, or plan to become pregnant while in the trial;
12. Be using an unreliable form of contraception (female subjects at risk of pregnancy only);
13. Be participating in another investigative drug trial, parallel to, or within 4 weeks of screening (Visit 0);
14. Have a known allergy to mannitol;
15. Be using non-selective oral beta blockers;
16. Have uncontrolled hypertension –i.e. systolic BP > 190 and / or diastolic BP > 100;
17. Have a condition or be in a situation which in the Investigator’s opinion may put the subject at significant risk, may confound results or may interfere significantly with the subject’s participation in the trial;or
18. Have a failed or incomplete MTT at trial entry (as evaluated in Section 8.1.1.1).



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

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 17.1 Level: LLT Classification code 10011764 Term: Cystic fibrosis NOS System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Trade Name: Bronchitol
Product Name: Bronchitol
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Mannitol
Other descriptive name: MANNITOL
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control (50mg b.i.d.) for improving lung function as measured by mean change from baseline FEV1 (mL) over the 26-week treatment period in adult subjects with cystic fibrosis (CF).

Primary end point(s): The primary endpoint is the mean change in FEV1 (mL) from baseline (Visit 1) over the 26-week treatment period (to Visit 4).

Secondary Objective: 1. To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control for improving lung function as measured by mean change from baseline FVC (mL) over the 26-week treatment period in adult subjects with CF;
2. To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control in increasing the time to first pulmonary exacerbation over the 26-week treatment period in adult subjects with CF;
3. To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for reducing the number of days on antibiotics due to pulmonary exacerbation (oral, inhaled or IV);
4. To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for decreasing the number of days in hospital due to pulmonary exacerbation; and
5. To determine whether inhaled mannitol (400 mg b.i.d.) decreases the rate of pulmonary exacerbations over the 26-week treatment period compared to control in adult subjects with CF.

Timepoint(s) of evaluation of this end point: visit 1 and visit 4

Secondary Outcome(s)

Secondary end point(s): • Mean change from baseline FVC (mL) over the 26-week treatment period;
• Time to first pulmonary exacerbation over the 26-week treatment period;
• Rate of pulmonary exacerbations over the 26-week treatment period;
• Number of days in hospital due to pulmonary exacerbation;
• The incidence of pulmonary exacerbations;
• Number of days on antibiotics (oral, inhaled or IV) due to pulmonary exacerbation;
• Ease of expectoration measured using a visual analogue scale; and
• CFQ-R respiratory domain score.

Timepoint(s) of evaluation of this end point: Throughout the 26 week treatment period

Secondary ID(s)

DPM-CF-303

2013-005357-79-CZ

Source(s) of Monetary Support

Pharmaxis Limited