Statins To Treat Adult Cystic Fibrosis (CFStatin)

Statins To Treat Adult Cystic Fibrosis (CFStatin)




Sponsor:
University of British Columbia

Information provided by:
University of British Columbia

ClinicalTrials.gov Identifier:
NCT01092572

Purpose
Cystic fibrosis (CF) is a lethal genetic condition that affects 30,000 children and adults in the United States. Although CF management has improved substantially over the past two decades, there is still no cure and most patients with CF die before reaching their 50th birthday, largely due to lung failure. There is growing evidence that excess lung and blood inflammation that occurs in response to infections in the lungs cause CF patients to be sicker. Simvastatin is a drug that is used to lower cholesterol, but many researchers have found that this drug may also treat blood and lung inflammation. In this study, we will determine whether or not simvastatin can treat blood and lung inflammation in patients with CF and most importantly determine whether or not it can make these patients feel better and have better lung function.

Cystic FibrosisSystemic Inflammation
Drug: SimvastatinDrug: placebo

Phase IPhase II

Study Type:
Interventional

Study Design:
Allocation: RandomizedControl: Placebo ControlEndpoint Classification: Efficacy StudyIntervention Model: Parallel AssignmentMasking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)Primary Purpose: Treatment

Official Title:
The Effect of Simvastatin on Systemic Inflammation in Adult Cystic Fibrosis Subjects: A Pilot Study

Primary Outcome Measures:
C-reactive protein [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The difference in the change in plasma C-reactive protein concentrations from baseline to 12 weeks of treatment between those randomized to simvastatin 40 mg/d and those randomized to placebo

Secondary Outcome Measures:
Changes in forced expiratory volume in one second (FEV1) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The differences in the above parameters over 12 weeks between those assigned to simvastatin 40 mg/d and those assigned to placebo.
Changes in exacerbation rates [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The differences in the above parameters over 12 weeks between those assigned to simvastatin 40 mg/d and those assigned to placebo.
Changes in blood pro-inflammatory markers such as IL-6, TNF, IL-1beta, LPS, LBP, sCD14, EndoCAB, SP-D, CCL-18) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The differences in the above parameters over 12 weeks between those assigned to simvastatin 40 mg/d and those assigned to placebo.

Estimated Enrollment:
120

Study Start Date:
May 2010

Estimated Study Completion Date:
July 2012

Estimated Primary Completion Date:
January 2012 (Final data collection date for primary outcome measure)


Simvastatin 40 mg/d: Experimental
simvastatin 40 mg per day taken orally

Drug: Simvastatin
simvastatin 40 mg per day orally for 12 weeks.
Sugar pill: Placebo Comparator

Study Objectives
To determine the effect of 12 weeks of 40 mg once daily simvastatin on general inflammatory molecules, IL-6 and CRP in the blood of CF patients.
To determine the effect of simvastatin on LPS-related pathway molecules in the blood.
To determine the effect of simvastatin on inflammatory pneumo-proteins in the blood.
To determine exacerbation and safety data on statins in preparation for a large phase III trial of statins in CF.

Study Endpoints
The primary endpoint will be the quantitative changes in serum levels of CRP.
Secondary endpoints will include:
blood biomarkers IL6, LPS related proteins, LPS, LBP, sCD14 and EndoCAb, and pneumoproteins, SPD and CCL18; and molecules such as TNF-α and IL-1beta;
changes in FEV1 over 12 weeks ; and
exacerbations over 12 weeks

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092572
Contacts
Contact: Don D Sin, MD
604-806-8395
don.sin@hli.ubc.ca
Contact: Paul Man, MD
604-806-8495
pman@providencehealth.bc.ca
Locations
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 1Y6
Sponsors and Collaborators
University of British Columbia
Investigators
Principal Investigator:
Paul Man, MD
University of British Columbia
More Information
No publications provided
Responsible Party:
University of British Columbia ( Shu-Fan Paul Man, Professor of Medicine )

Galapagos to build cystic fibrosis drug pipeline

Galapagos to build cystic fibrosis drug pipeline

Click here to access the live audio webcast R&D Update presentation today at 13.00 CET/8 AM EST, call number +32 2290 1791

Mechelen, Belgium; 19 March 2010 – Galapagos NV (Euronext: GLPG) announced the decision to pursue cystic fibrosis (CF) in its strategy to deliver breakthrough medicines to patients with orphan diseases. Details of Galapagos’ CF program and its pipeline of 4 clinical and over 50 pre-clinical and discovery programs will be discussed during the R&D Update presentation webcast later today.

Over the past years, Galapagos has established a strong franchise in orphan diseases. Galapagos has applied its proprietary target discovery platform in collaborations with the CHDI (for Huntington’s disease), the Cystic Fibrosis Foundation and the ALS Foundation. In addition, Galapagos is evaluating its SARM candidate drug, GLPG0492, for the treatment of Duchenne muscular dystrophy.

“Orphan diseases represent significant unmet clinical needs. The lack of novel disease-modifying therapies for these diseases presents significant opportunities for a company capable of delivering new mode-of-action therapies. Galapagos has made a strategic decision to pursue cystic fibrosis as the first orphan disease in which we will discover, develop and launch our own medicines. This decision is based on our successful collaboration with the CF Foundation, through which we have identified the first ever disease-modifying targets for CF,” said Onno van de Stolpe, CEO of Galapagos. “With this strategy, Galapagos expects to benefit from the accelerated approval procedures and exclusive commercial rights granted to developers of orphan drugs through US and European regulatory agencies, to ultimately provide real medical benefit to this sizeable population of patients.”

The CF Foundation and Galapagos entered a target discovery collaboration in 2005, which resulted in 19 novel disease-modifying targets that have been validated in the standard pre-clinical model for this disease. Galapagos has secured all rights to these targets and has started to develop small molecule therapies against a select group of these targets. Galapagos will retain intellectual property and commercial rights on any compounds reaching the market. Galapagos medicines in CF will be disease-modifying agents with clear efficacy benefits relative to existing therapies, which only treat the symptoms of the disease. A first pre-clinical candidate is scheduled to be nominated by 2013.

“We are confident that the strategic decision to enter CF drug discovery will provide new treatment options for CF patients and thus create long term value for our shareholders. In the first years, research expenses for this new strategy will be limited and we anticipate that the clinical trials to support approval can be financed by our strengthening cashflow,” said Van de Stolpe.

Conference call and webcast presentationGalapagos will conduct a conference call open to the public today at 13.00 Central European Time (CET), which will also be webcast. To participate in the conference call, please call +32 2290 1791 ten minutes prior to commencement. A question and answer session will follow the presentation of the results. Click here to access the live audio webcast. The archived webcast also will be available for replay shortly after the close of the call.About cystic fibrosisCystic fibrosis (CF) is a hereditary disease of the entire body which leads to severe disability and early death in many cases. Symptoms include frequent lung infections, sinus infections, poor growth, and diarrhea. The cause is a defect in gene which encodes for cystic fibrosis transmembrane conductance regulator (CFTR), a protein which regulates components of sweat, mucus, and digestive juices. CF affects approximately 70,000 people worldwide. Patient symptoms are treated with antibiotics and other medicines, with the global market expected to double from just over $1 billion in 2010 to $2 billion by 2015. There currently is no cure for the disease, and most patients die in their 30s due to lung failure. More info at: www.cff.org/AboutCF

About Galapagos Galapagos (Euronext: GLPG; OTC: GLPYY) is a mid-size biotechnology company specialized in the discovery and development of small molecule and antibody therapies with novel modes-of-action. The Company is progressing one of the largest pipelines in biotech, with four clinical and over 50 small molecule discovery/pre-clinical programs. Through risk/reward-sharing alliances with GlaxoSmithKline, Lilly, Janssen Pharmaceutica, Merck & Co. and Roche, Galapagos is eligible to receive up to €3 billion in downstream milestones, plus royalties. With the acquisition of Argenta, Galapagos now has more than 670 employees and operates facilities in six countries, with global headquarters in Mechelen, Belgium. More info at: www.glpg.com

CONTACT

Galapagos NVOnno van de Stolpe, CEOTel: +31 6 2909 8028
Elizabeth Goodwin, Director Investor RelationsTel: +31 6 2291 6240ir@glpg.com

Plugs (WARNING! PICTURES)

Well I know many of us adult CFer's have been talking about "what is a plug?" lately.

My definition has always been taking a green/brown jelly bean, popping it in your mouth, chew once, twice, maaaaaaybe 3 times and WHAM! you have a plug.

If you want pictures, here you go. I'd love to hear comments about how this compares to your plugs:

Changes in cystic fibrosis sputum microbiology in the United States between 1995 and 2008

Pediatr Pulmonol. 2010 Mar 15.

Changes in cystic fibrosis sputum microbiology in the United States between 1995 and 2008.

Emerson J, McNamara S, Buccat AM, Worrell K, Burns JL.

Seattle Children's Hospital, Seattle, Washington.

STUDY OBJECTIVES: The study objective was to identify changes in cystic fibrosis (CF) sputum microbiology over 13 years.

METHODS: This study recruited a contemporary cohort of CF patients meeting similar eligibility criteria as the 520 subjects in the Phase 3 trials of inhaled tobramycin (historical cohort). Subjects submitted a single sputum specimen to a centralized laboratory for culture and susceptibility testing. Data were summarized and cross-sectional prevalence estimates were compared between cohorts. Exploratory analyses examined associations between recent antibiotic exposures and resistance prevalence.

RESULTS: Sputum samples from 267 subjects from 33 US CF centers were submitted for testing. A total of 656 Pseudomonas aeruginosa isolates were identified from 253 culture-positive subjects. Comparison between cohorts revealed an increase in the prevalence of subjects with tobramycin resistant (11.8% vs. 30.4%, P < 0.001) and amikacin resistant (24.2% vs. 42.7%, P < 0.001) P. aeruginosa. Prevalence of ciprofloxacin resistance was similar (34.4% vs. 33.6%, P = 0.81). Within the contemporary cohort, potential associations between recent antibiotic exposures and prevalence of P. aeruginosa resistance were examined; findings included that exposure to intravenous carbapenems was significantly associated with aztreonam resistance, meropenem resistance, and multidrug resistance (P = 0.0002, P = 0.0003, and P = 0.0002, respectively). Prevalences of Staphylococcus aureus, methicillin-resistant S. aureus, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans were also increased in the contemporary cohort.

CONCLUSIONS: We identified important changes in the patterns of CF airway microbiology, including increased aminoglycoside resistance and prevalence of other antibiotic resistant organisms. These changes are concerning to clinicians caring for individuals with CF because they impact treatment options. These data point to a critical need to develop new antimicrobials for CF. Pediatr Pulmonol. (c) 2010 Wiley-Liss, Inc.

FDA grants "orphan drug" status to Bayer's Ciprofloxacin dry powder inhaler

FDA grants "orphan drug" status to Bayer's Ciprofloxacin dry powder inhaler for cystic fibrosis

11 March 2010


Mumbai: Bayer Schering Pharma AG, Germany, today said that the US Food and Drug Administration had granted an orphan drug designation for its ciprofloxacin dry powder inhaler (DPI) used in the management of chronic pulmonary infections due to Pseudomonas aeruginosa in cystic fibrosis (CF) patients.

European Medicines Agency (EMA) has already granted a similar designation to Ciprofloxacin DPI, an innovative drug-device combination.

The DPI combines ciprofloxacin dry powder that is formulated using Novartis' Proprietary PulmoSphere technology with an easy-to-use delivery inhaler.

Ciprofloxacin DPI is currently in Phase II development and is being studied for its safety and potential to improve lung function, as measured by the forced expiratory volume in 1 second (FEV1), in patients with CF.

''Receiving the orphan drug designation by the FDA for ciprofloxacin DPI is positive news for patients with this life-threatening disease,'' said Dr. Jean-Philippe Milon, head of global business unit, general medicine, Bayer Schering Pharma AG. ''With ciprofloxacin DPI, we are investigating a promising and convenient treatment option for CF patients worldwide.''

Cystic fibrosis is a life-threatening inherited disease affecting the lungs, pancreas, liver, and intestines. Approximately 30,000 patients in the USA are affected by CF. In 2008, the median age of survival for patients in the USA was 37.4 years according to data compiled by the Cystic Fibrosis Foundation. The major consequences of the disease are pancreatic insufficiency and reduced lung function. Lung disease accounts for about 90 per cent of the mortality associated with CF. Patients with cystic fibrosis have dehydrated, thickened respiratory secretions that are difficult to clear and provide an attractive environment for bacteria, thus increasing the risk of infection and inflammation.

Pulmonary infections in CF patients are a chronic problem and represent the leading cause of exacerbations and mortality. P. aeruginosa is the leading pathogen in CF patients. The thick mucus in the lungs is ideally suited to bacteria, and individuals with CF are colonised and infected by bacteria from an early age; about 20 per cent of children under 1 year of age and 80 per cent of adult patients with CF have P. aeruginosa present in their sputum. Chronic infection with is associated with an accelerated decline in pulmonary function, more frequent exacerbations, and increased mortality in patients with CF.

Novel therapeutic strategies are needed. Current therapies are not curative and CF patients continue to experience significant exacerbations, morbidity, and mortality while on therapy.
Clinical Trials with Ciprofloxacin DPIAccording to Bayer, in Phase I studies with ciprofloxacin DPI in paediatric and adult CF patients, ciprofloxacin has been shown to reach high concentrations in the lung with very low systemic exposure following single and multiple dose administration.

"Initial Phase I study results showed that ciprofloxacin DPI was well tolerated in CF patients without clinically relevant drug treatment related adverse effects," a statement from the company said.

"A multinational Phase II study in CF patients is ongoing with the primary end point of improvement in lung function, measured by FEV1. Additionally, a Phase II study investigating the impact of ciprofloxacin DPI on overall bacterial load and clinical outcomes in patients with non-CF bronchiectasis is also ongoing," the statement added.

Cystic fibrosis disease severity and haemochromatosis gene mutations.

Respirology. 2010 Jan;15(1):141-9.

Population-based study of cystic fibrosis disease severity and haemochromatosis gene mutations.

Pratap U, Quinn S, Blizzard LB, Reid DW.

Respiratory Research Group, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.

ABSTRACT Disease outcomes in CF may be very variable despite identical genotypes, environments and infecting organisms. This study provides evidence to support a disease-modifying role for haemochromatosis gene mutations. These effects are most likely mediated through alterations in systemic iron homeostasis.

Background and objective: Haemochromatosis (HFE) mutations increase the risk of bowel obstruction in cystic fibrosis (CF), but the impact on other disease manifestations is unknown. Methods: We determined the prevalence of HFE mutations (C282Y and H63D) in the Tasmanian CF population and assessed the relationship to systemic iron stores, Pseudomonas aeruginosa infection, lung disease severity and prevalence of diabetes.

Results: DNA was obtained from 82 individuals (96% of the entire CF population); 19 (23.2%) were H63D heterozygotes, three (3.7%) were H63D homozygotes and two patients were compound C282Y/H63D (2.4%). Seven (8.5%) patients were heterozygous for the C282Y mutation. Overall, 31 (37.8%) patients carried a HFE mutation. CF patients possessing HFE mutations had significantly better iron stores than non-carriers (P < 0.05). The mean slopes of annual decline in FEV1 and FVC % predicted were significantly steeper in HFE carriers compared with non-carriers (P < 0.01). Patients with HFE mutations were more likely to have had childhood bowel obstruction (RR 2.44, 95% CI: 1.04-5.74, P < 0.05). Diabetes was more common in HFE carriers (RR 2.96, 95% CI: 0.99-8.8, P = 0.05), but this effect attenuated when corrected for age (RR 2.89, 95% CI: 0.91-9.21, P = 0.07).

Conclusions: HFE gene mutations modify disease severity in CF, through probable effects on iron homeostasis.