cystic fibrosis subjects with chronic pulmonary infection with Pseudomonas aeruginosa MedDRA version: 13.1 Level: PT Classification code 10011763 Term: Cystic fibrosis lung System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 13.1 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Colobreathe
Product Code: N/A
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Colistimethate sodium
CAS Number: 8068288
Other descriptive name: Colistimethate s
Sponsors
Forest Laboratories UK Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female subjects aged 6-60 years. • Subjects must have a documented diagnosis of Cystic Fibrosis from a specialist CF Unit (genotype and/ or positive sweat tests). • If the subject is female and post-menarche/ pre-menopausal and heterosexually active, the patient must be using adequate effective contraceptive methods. • Subjects will have documented microbiological evidence of “chronic pulmonary infection” with PA infection (including colonisation), defined as either: (i) = 50% samples (minimum of 3 samples: sputum samples or throat swabs) positive for PA over the previous 12 months prior to the first day of trial medication administration (Visit 1) OR (ii) two samples (sputum samples or throat swabs) positive for PA over the previous 6 months prior to the first day of trial medication administration (Visit 1). • Subjects are required to be non-smokers or a past smoker who has not smoked within the past 12 months prior to the first day of trial medication administration (Visit 1). • Each subject or parent/guardian must be capable of reading and understanding informed consent and the trial information leaflet (or simplified assent document for those under the legal contractual age of consent and able to read) and understand and must have granted his or her written informed consent (or assent as appropriate) before any trial procedure is carried out. • Current CF condition must be clinically stable in the investigator’s opinion i.e. there must be no evidence of a current acute respiratory exacerbation within 7 days prior to the first day of trial medication administration (Visit 1). • Subjects with an FEV1 predicted, greater than 25%. Lung function anticipated in the opinion of the investigator to be clinically stable for the duration of the study. • Subjects should continue with all pre-existing medications unless specified in the protocol exclusion criteria (4.2). Changes are to be recorded in the CRF with reasons. 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Evidence of an acute respiratory exacerbation within 7 days prior to the first day of trial medication administration (Visit 1). The protocol definition of an acute respiratory exacerbation is the presence of at least four of the following: (i) Change in appearance of sputum (i.e. increased purulence or volume). (ii) Increased productive cough, dyspnoea or respiratory rate. (iii) Progressive physical findings (crackles, rhonchi and air exchange) on chest auscultation. (iv) New (infiltrates) intrusion on chest X-ray. (v) Lassitude and decreased exercise tolerance. (vi) Fever (=38oC). (vii) Deterioration of 10% of highest FEV1 score obtained in the last 6 months. (viii) Decreased appetite. (ix) Emergence of new pathogen in sputum i.e. a pathogen that causes clinical disease. If a subject has less than four of the above and receives a course of intravenous antibiotics, or if there is an unscheduled course without clear evidence of an acute pulmonary infective exacerbation, then this is considered an acute exacerbation and an exclusion criterion. • Known allergy/hypersensitivity (or previous intolerance) to colistimethate sodium, or any inhaled dry powder pharmaceutical. • Administration of any investigational product within 28 days prior to first trial medication administration (Visit 1). • Subjects who have received treatment that has permanently reduced PA infection status will not be included (e.g. effective anti-pseudomonal vaccination and gene therapy). • Subjects who are or will be receiving a planned/scheduled course of elective iv antibiotic therapy during the course of the study. • Subjects who have received iv colistin in previous 28 days. • Subjects receiving inhaled antibiotics (Colistin, colistimethate, TOBI, aztreonam, ciprofloxacin, levofloxacin or other aminoglycoside in the previous 72hrs prior to study drug administration. All subjects will be washed out from inhaled antibiotic medication for 3 days prior to study entry. • Subjects who are infected with Burkholderia or have active allergic bronchopulmonary aspergillosis (ABPA). • Existence of any pre-study medical conditions which, in the judgement of the investigator, warrant exclusion from the study. Pre existing renal impairment is not an exclusion criterion. • Subjects who are pregnant or breast-feeding, or who plan to become pregnant during the study period. • Inability to communicate or cooperate with the investigator due to language problems, poor mental development or impaired cerebral function. • Inability to comply with any of the study procedures or the study regimen (including inability to use Colobreathe® inhaler i.e. Turbospin® device for duration of the trial). • Screening laboratory parameters falling outside the expected normal ranges for CF (investigator decision). • Evidence of significant hepatic impairment (investigator decision) • Subjects who in the opinion of the investigator are unsuitable for any reason to participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the magnitude of systemic exposure to colistimethate after repeat dosing with Colobreathe® in adult, adolescent and paediatric subjects with cystic fibrosis.;Secondary Objective: • To establish the full PK profile of the drug substance • To monitor the safety of Colobreathe® after 7 days repeat dosing • To compare microbiological and LC/MS/MS assays for the detection of colistin/colistimethate • To estimate treatment compliance • To assess changes in FEV1 % predicted;Primary end point(s): The primary endpoint is the PK profile of the drug substance colistimethate, colistin A and colistin B in plasma, and urine, including plasma Cmax and Tmax in paediatric, adolescent and adult subjects. Also sputum samples will be collated to confirm that drug has been inhaled during administration. | — |
Countries
Germany, Poland, United Kingdom
Outcome results
None listed