Determination of the pharmacokinetics of inhaled mannitol after single and multiple dosing in cystic fibrosis patients

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-008228-34-GB
• Date of registration: 29/07/2010
• Prospective Registration: No
• Primary sponsor: Pharmaxis Ltd
• Public title: Determination of the pharmacokinetics of inhaled mannitol after single and multiple dosing in cystic fibrosis patients
• Scientific title: Determination of the pharmacokinetics of inhaled mannitol after single and multiple dosing in cystic fibrosis patients
• Date of first enrolment: 28/01/2009
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-008228-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
•Have given written informed consent to participate in this study in
accordance with local regulations
• Have a confirmed diagnosis of cystic fibrosis (sweat test and/or genotype)
• Be aged >6 years (6–11 for paediatrics, 12–17 for adolescents and greater than or equal to 18 years for adults)
• Have FEV1 > 30 % and < 90% predicted
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:
• Be investigators, site personnel directly affiliated with this study, or their
immediate families. Immediate family is defined as a spouse, parent, child
or sibling, whether biologically or legally adopted.
• Be considered “terminally ill” or listed for lung transplantation
• Have had a lung transplant
• Be using nebulised hypertonic saline
• Have had a significant episode of haemoptysis (> 60 mL) in the three
months prior to enrolment
• Have had a myocardial infarction in the three months prior to enrolment
• Have had a cerebral vascular accident in the three months prior to
enrolment
• Have had major ocular surgery in the three months prior to enrolment
• Have had major abdominal, chest or brain surgery in the three months prior
to enrolment
• Have a known cerebral, aortic or abdominal aneurysm
• Be breast feeding or pregnant, or plan to become pregnant while in the
study
• Be using an unreliable form of contraception (female patients at risk of
pregnancy only)
• Be participating in another investigative drug study, parallel to, or within 4
weeks of study entry (except inhaled mannitol)
• Not able to maintain a mannitol free diet from Day -2 until Day 8 of the
treatment phase.
• Have a known allergy to mannitol
• Be using beta blockers
• Have uncontrolled hypertension – systolic blood pressure > 190 and / or
diastolic blood pressure > 100
• 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 patient’s participation in the study
• Be MTT positive.


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

Health Condition(s) or Problem(s) studied

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

Intervention(s)

Product Name: IDPM: Inhaled Dry Powder Mannitol
Product Code: IDPM
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: MANNITOL
CAS Number: 69658
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

Primary end point(s): The following PK endpoints will be calculated for the completed subjects:
• Day 1 and 2 (pre-dose Day 1 to 24 h post-dose):
Cmax, tmax, AUC0-12h, AUC0-infinity, kel, t½, C12h
• Day 7 and 8 (pre-dose Day 1 to 24 h post-dose):
Cmax, tmax, AUC0-12h, kel, t½, Cpre-dose, C12h

Safety Endpoints:

• serious adverse events,
• treatment related adverse events (defined as being possibly, probably or
definitely related to treatment in the opinion of the investigator),
• treatment related serious adverse events,
• adverse events leading to study withdrawal,
• treatment related adverse events leading to study withdrawal, and
• deaths

Main Objective: The general objective of the study is to estimate the systemic pharmacokinetics of mannitol after single and multiple dosing of IDPM 400 mg to adult and paediatric cystic fibrosis patients. The specific objectives are as follows:

Primary Objectives-

• Determine the pharmacokinetic parameters of mannitol in adult and paediatric CF patients after a single dose of IDPM
• Determine the pharmacokinetic parameters of mannitol in adult and paediatric CF patients after twice daily dosing of IDPM for 5 days
• Compare PK of mannitol in adult and paediatric CF patients after single and multiple dosing of IDPM.

Secondary Objective: • Clinical safety of IDPM in adult and paediatric CF patients after single and multiple dosing.

Secondary ID(s)

DPM-PK-102