A Phase I/II randomised, placebo-controlled, double blind trial to assess the safety, tolerability, pharmacodynamics and exploratory efficacy of heparin 25 mg inhalation powder in adults with Cystic Fibrosis (CF) - VR496/005- Orally inhaled heparin in adults with Cystic Fibrosis

• Conditions: Cystic Fibrosis; MedDRA version: 9.1Level: LLTClassification code 10011763Term: Cystic fibrosis lung

• Registration Number: EUCTR2007-006276-11-IE
• Lead Sponsor: Vectura Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-11
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. Male or female = 18 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. FEV1 40 - 80% of predicted value for age, sex and height; during 6 months prior to Screening;
6. FEV1 within 10% of best value during 6 months prior to 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? 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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.Evidence of clinically significant haemoptysis (i.e., bright red blood or substantial blood clot in sputum);or an increased risk of developing haemoptysis by virtue of previous clinical history of clinically significant 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 < 100 x 106 cells/mL and / or; iii) Prothrombin time (PT) > 25% above the upper limit of normal (ULN) (i.e., 18.8s);
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 of 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. Any vaccination within 1 month of Screening;
11. 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 mg/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) 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); ii) use of mucolytics (e.g., Pulmozyme®, erdosteine). Patients must be off Pulmozyme® for 1 month prior to Baseline (Day 1) and during the treatment period; iii) concomitant use of hypertonic saline treatment (Note: Patients treated with Pulmozym

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified