Cystic Fibrosis MedDRA version: 9.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung
Conditions
Interventions
Product Name: Heparin 25mg inhalation powder, hard capsule
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: HEPARIN SODIUM
CAS Number: 9041081
Concentration unit: IU/mg intern
Sponsors
Vectura Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female = 16 years; 2. Non-smoker; 3. Written informed consent obtained prior to any trial specific procedures; 4. Confirmed diagnosis of CF lung disease (i.e., respiratory clinical symptoms and positive sweat test or disease inducing mutations) by CF expert / Investigator; 5. Patient considered, in the Investigator’s opinion, to be clinically stable and has at Screening and Baseline an FEV1 40 - 90% of predicted value for age, sex and height; 6. FEV1 value at Baseline is within +/-15% of FEV1 value 4 weeks earlier at Screening; 7. Regular mucus production due to CF; 8. Ease of sputum expectoration (i.e., clearability) VAS score of = 80 mm; 9. Neutrophil elastase and / or IL-8 levels above detectable levels and/or upper limit of normal range for specified laboratory; 10. Adequate contraceptive measures (the subject [and his/her partner] should use adequate contraceptive measures, consisting of two forms of contraception, at least one of which must be a barrier method); 11. Able to comply with all the requirements of the protocol; 12. Able to use inhaler satisfactorily. 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: 1. Known sensitivity to any preparation of inhaled or parenteral heparin or the excipient leucine; 2. Any contra indication to Monoparin® considered clinically relevant; 3. Increased bleeding risk defined as any of : a. Any history of or current evidence of clinically significant haemoptysis (i.e., bright red blood or substantial blood clot in sputum) or any other clinically important signs, symptoms or features of haemoptysis which in the opinion of the patient’s Consultant Physician/Investigator responsible for the care of the patient and management of his/her CF are considered clinically significant and/ or liable to lead to an increased risk of developing haemoptysis; b. Haemorrhage of any major organ 6 months prior to Baseline (Day 1); c. Patients with active gastrointestinal ulcer / bleeding during 6 months prior to Baseline (Day 1); d. History of heparin-induced thrombocytopaenia; e. Patients with bleeding diathesis defined by: i) aPTT > 25% above normal (26-36 seconds) and / or; ii) Platelet count 25% above the upper limit of normal (ULN) (i.e., 18.8 s); f. Evidence of portal hypertension (e.g., hypersplenism or known Grade III/IV oesophageal varices; 4. Clinically significant liver disease (e.g., known severe liver disease or cirrhosis, raised serum transaminases [ALT, AST] more than 2 x ULN), which in the opinion of the Investigator would impose a significant clinical risk; 5. Clinically significant serious disease or organ system disease not currently controlled / stable on present therapy; 6. Patients with a history a clinically or radiologically diagnosed aspergilloma; 7. Pregnancy at Screening; or lactation; 8. Planned hospitalisations which could interfere with trial compliance; 9. Previous thoracic or scheduled major surgery during trial period; 10. Previous or current regular use of proscribed medication defined as: a. Chronic / regular non-steroidal anti-inflammatory drug (NSAID) use (i.e., more than 3 times per week); b. Any regular anti coagulant therapy (e.g., warfarin, aspirin) in the 2 weeks prior to Screening; c. Any previous use of inhaled heparin; d. Use of parenteral heparin 1 month prior to Screening; e. Use of other investigational drugs 1 month prior to Screening; f. Chronic / regular corticosteroid (1 month prior to Screening) use except for: i) inhaled corticosteroids = 1 mg/day of beclometasone dipropionate (BDP) or equivalent (e.g., 500 ug/day Seretide); Note: It is acceptable for the dose to be reduced 1 month prior to and during Screening as long as this lower dose subsequently remains stable. ii) systemic doses of = 5 mg/day of oral prednisolone or equivalent; iii) limited dermatological use (a maximum of 3 times per week); g. Any regular inhaled tobramycin (Tobi®) or other antibiotic use for oral, inhaled or parenteral treatment to be stable for at least 1 month prior to Screening and during the course of the trial (e.g., erythromycin, clarithromycin; azithromycin; colistin). (Note: If dosing changes between Screening and Baseline (Day 1), the patient can not be entered in the trial); h. Modification of medication to treat respiratory disease between Screening and Baseline (Day 1) i.e. administration of additional medication for a respiratory infection such as antibiotics (e.g., any inhaled antibiotic such as Tobi® and colistin or any oral or parenteral antibiotic); i. Patients prescribed mucolytics, or hypertonic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and tolerability of heparin 25 mg, inhalation powder, hard capsules in patients with CF.;Secondary Objective: Pharmacodynamic investigation of: Expectorated mucus (rheological). Effects on sputum inflammatory markers (neutrophil elastase, IL-6, -8, total cell count, % neutrophils, % macrophages; effect on pH in exhaled breath condensate may be measured; on inflammatory blood markers (neutrophil elastase, neutrophil elastase / alpha-1 antitrypsin complex, IL-6, -8, neutrophil count, C reactive protein); coagulation (aPTT, platelets). Evaluate efficacy by VAS based on change in symptoms: cough resolution; expectorated sputum clearability, thickness, volume, colour, viscoelasticity; breathlessness; general well being. Microbiology of sputum for effects on bacterial growth, density, antibiotic sensitivity (ID, culture, density, sensitivity of P aeruginosa, B cepacia, H influenzae and S aureus). Volume and weight of 24-h expectorated sputum sample. Pulmonary function ;FEV1, FVC, forced mid-expiratory flow (FEF25-75), arterial oxygen saturation (SaO2). Response to the CF Questionnaire.;Primary end point(s): Pharmacodynamic Endpoints The PD variables are: Expectorated mucus measurement parameters (i.e., rheological viscoelasticity / physicochemical measurement parameters) (in accordance with advised tests) (expectorated sputum samples must be collected after standard physiotherapy regime); Induced sputum markers (neutrophil elastase, interleukins [IL-6, IL-8]) and cell counts (i.e. total cell counts, % neutrophils, % macrophages); EBC levels of pH may be measured at selected sites); Blood markers, neutrophil elastase, neutrophil elastase / AAT complex, neutrophil count, IL-6, IL-8 and CRP levels; aPTT and platelets. Evaluation of Efficacy Endpoints The efficacy variables are: VAS parameters, i.e., cough resolution; expectorated sputum clearability, thickness, volume, colour, viscoelasticity (stickiness); breathlessness; general | — |
Countries
Ireland, Italy, United Kingdom
Outcome results
None listed