- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02212431
First Study of Oral Cysteamine in Cystic Fibrosis
An Open Label Investigation of the Tolerability and Pharmacokinetics of Oral Cysteamine in Adults With Cystic Fibrosis.
The morbidity and mortality associated with Cystic Fibrosis (CF) are the result of chronic suppurative lung disease. The aggressive use of antibiotics is one of the mainstays of treatment in CF, however, the problems of multiple drug resistance and adverse reactions are major clinical issues.
Cysteamine is a licensed drug used in the treatment of cystinosis. In vitro work suggests that cysteamine has properties of potential benefit in CF. Cysteamine is a potent mucolytic, it disrupts biofilms, it is antimicrobial, and synergises with other antibiotic agents. CF is characterised by malabsorption and it is not known whether cysteamine is absorbed in CF, furthermore it is not known if cysteamine enters the bronchial secretions. It is not possible to assume that the pharmacokinetics of cysteamine in patients with CF are the same as those reported for cystinosis.
Objectives: to characterise the pharmacokinetic profile of cysteamine in people with CF, to ascertain whether cysteamine enters the bronchial secretions and the tolerability of cysteamine by patients with CF.
Method: a single centre, single group open label investigation of the tolerability and pharmacokinetics of oral cysteamine (Cystagon) when administered to patients with Cystic Fibrosis at the dose licensed for use in cystinosis.
Setting: adult CF clinic, Aberdeen Royal Infirmary.
Target population: 12 patients aged ≥18years with CF associated lung disease who are clinically stable.
Intervention: Oral cysteamine (Cystagon) will be increased from 450mg od to 450mg qds over three weeks, they will remain on 450mg qds for two weeks.
Assessment: face to face health outcome assessments will be carried out for all participants at recruitment/baseline, 1, 2, 3, and 5 and 6 weeks. Serial blood cysteamine levels will be measured in the first 24 hours after the first dose. Sputum cysteamine will be quantified after two weeks of full dose cysteamine 450mg qds. Disease specific health status (CFQ-R) will be assessed at baseline and after two weeks of full dose. At each assessment, lung function (FEV1, FVC), adverse reactions and serious adverse events will be ascertained. Blood samples will be taken for measurement of haematological and biochemical parameters. Sputum samples at each assessment will be analysed for microbial load and spinnbarkeit.
Study Overview
Detailed Description
Cystic Fibrosis (CF) is the commonest fatal inherited disease in Caucasian populations of European origin. The morbidity and mortality associated with CF are the result of chronic suppurative lung disease. The lungs of people with CF are chronically infected with bacteria that cause chronic infection and acute periods of worsening infection known as exacerbations. Many of the bacteria that infect patients with CF are intrinsically resistant to many antibiotics and bacterial antibiotic resistance is increasing, in addition many of the pathogenic bacteria grow in biofilms that contributes to antibiotic resistance. The aggressive use of antibiotics to suppress chronic infection and to treat acute exacerbations is one of the mainstays of treatment in CF that has contributed to the increased survival of CF patients. However, the problems of multiple drug resistance and adverse reactions are major clinical issues. This has led to calls for research into new antibiotics and new antibiotic strategies to target the biofilm and to increase the effectiveness of currently available antibiotics.
Cysteamine is a licensed drug used in the treatment of cystinosis for more than 20 years. Laboratory based work suggests that cysteamine may be a beneficial adjunct to conventional antibiotic treatment in CF. Cysteamine is a potent mucolytic, it disrupts biofilms, it is antimicrobial, and synergises with other antibiotic agents, broadening their spectrum of activity, delivers a post-antimicrobial effect and reverses antibiotic resistance (even in multi-drug resistant bacteria). Although the pharmacokinetic characteristics of cysteamine are well established in people with cystinosis, there are no such data for cysteamine in CF. CF is characterised by malabsorption and it is not known whether cysteamine is absorbed in CF, furthermore it is not known if cysteamine enters the bronchial secretions. It is not possible to assume that the pharmacokinetics of cysteamine in patients with CF are the same as those reported for cystinosis.
Hypothesis: Oral cysteamine will be absorbed into the vascular space and bronchial secretions after administration to people with Cystic Fibrosis.
Objectives: to characterise the pharmacokinetic profile of cysteamine in people with CF, to ascertain whether cysteamine enters the bronchial secretions and the tolerability of cysteamine by patients with CF.
Method: a single centre, single group open label investigation of the tolerability and pharmacokinetics of oral cysteamine (Cystagon) when administered to patients with Cystic Fibrosis at the dose licensed for use in cystinosis.
Setting: adult CF clinic, Aberdeen Royal Infirmary.
Target population: 12 patients aged ≥18years with CF associated lung disease who are clinically stable.
Intervention: as recommended for cystinosis, patients will be maintained on their normal CF medication. Oral cysteamine (Cystagon) will be increased from 450mg od to 450mg qds over three weeks, they will remain on 450mg qds for two weeks.
Assessment: face to face health outcome assessments will be carried out for all participants at recruitment/baseline, 1, 2, 3, and 5 and 6 weeks. Serial blood cysteamine levels will be measured in the first 24 hours after the first dose. Sputum cysteamine will be quantified after two weeks of full dose cysteamine 450mg qds. Disease specific health status (CFQ-R) will be assessed at baseline and after two weeks of full dose. At each assessment, lung function (FEV1, FVC), adverse reactions and serious adverse events will be ascertained. Blood samples will be taken for measurement of haematological and biochemical parameters that are recognised, but rare side effects of cysteamine. Sputum samples at each assessment will be analysed microbiologically (quantitative, antibiotic sensitivity and rheology) to assess effects of cysteamine on sputum microbiology, sputum collected prior to first dosing will be used to develop a laboratory based method to quantify cysteamine in sputum.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Aberdeen, United Kingdom, AB25 2ZN
- Aberdeen Royal Infirmary
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- CF related suppurative lung disease who expectorate sputum,
- Clinically stable for >4 weeks,
- Aged ≥18 years,
- Weight >50kg,
- Female participants of child bearing potential should be using a reliable form of contraception.
Exclusion Criteria:
- Hypersensitivity to the active substance, any form of cysteamine, or to any of the excipients.
- Hypersensitivity to penicillamine.
- Lung, liver transplant, on active transplant list.
- For women, current pregnancy or breast-feeding, or planned pregnancy during the study.
- Any other significant disease/disorder which, in the investigator's opinion, either puts the patient at risk because of study participation or may influence the results of the study or the patient's ability to participate in the study.
Study Plan
How is the study designed?
Design Details
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cysteamine
Dosing will be in accordance with licensed use of cysteamine for cystinosis, i.e. 450mg qds. Dose will be escalated: 450mg od for one week 450mg bd for one week 450mg tds for one week 450mg qds for two weeks |
Dose will be increased weekly from 450mg od to 450mg bd, to 450mg tds to 450mg qds, will remain on highest dose for 2 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Elimination rate constant [k]
Time Frame: 24 hours
|
Blood cysteamine prior to the initial dose on day 1 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours post-dose
|
24 hours
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Concentration of cysteamine in sputum at week 5
Time Frame: 3 hours after final dose
|
3 hours after final dose
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in weight from baseline at week 5
Time Frame: 5 weeks
|
5 weeks
|
Number of Participants with Serious and Non-Serious Adverse Events
Time Frame: 6 weeks
|
6 weeks
|
Change in FEV1, FVC from baseline at week 5
Time Frame: 5 weeks
|
5 weeks
|
Change in disease related health status from baseline at week 5 measured by CFQ-R
Time Frame: 5 weeks
|
5 weeks
|
Change in haematological and biochemical indices from baseline at week 5
Time Frame: 5 weeks
|
5 weeks
|
change in sputum microbiology from baseline at week 5
Time Frame: 5 weeks
|
5 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Graham Devereux, MD, University of Aberdeen
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3/001/14
- 2014-000284-40 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cystic Fibrosis
-
Hospital de Clinicas de Porto AlegreUnknownCystic Fibrosis | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in Children | Cystic Fibrosis With ExacerbationBrazil
-
University of Colorado, DenverCystic Fibrosis FoundationTerminatedCystic Fibrosis-related Diabetes | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in ChildrenUnited States
-
Royal College of Surgeons, IrelandThe Hospital for Sick Children; Imperial College London; Erasmus Medical Center; University College Dublin and other collaboratorsActive, not recruitingCystic Fibrosis | Adherence, Medication | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in Children | Cystic Fibrosis Liver DiseaseUnited Kingdom, Ireland
-
Herlev and Gentofte HospitalCopenhagen University Hospital, DenmarkActive, not recruitingMyocardial Infarction | Heart Diseases | Heart Failure | Stroke | Cystic Fibrosis | Heart Failure, Diastolic | Heart Failure, Systolic | Left Ventricular Dysfunction | Cystic Fibrosis-related Diabetes | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of Pancreas | Cystic Fibrosis, Pulmonary | Cystic...Denmark
-
The Hospital for Sick ChildrenCanadian Cystic Fibrosis FoundationActive, not recruitingCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in ChildrenCanada
-
Arrowhead PharmaceuticalsTerminatedCystic Fibrosis, PulmonaryAustralia, New Zealand
-
AzurRx SASCompletedCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of PancreasTurkey, Hungary
-
Dartmouth-Hitchcock Medical CenterTrustees of Dartmouth CollegeWithdrawnCystic Fibrosis-related Diabetes | Cystic Fibrosis Liver Disease | CF - Cystic FibrosisUnited States
-
University Hospital, BordeauxCompleted
-
University of PortsmouthUniversity Hospital Southampton NHS Foundation Trust; Loughborough University; Queen Alexandra HospitalTerminated
Clinical Trials on Cysteamine
-
National Institute of Diabetes and Digestive and...National Cancer Institute (NCI); National Center for Advancing Translational... and other collaboratorsCompletedNonalcoholic Fatty Liver Disease (NAFLD)United States
-
Horizon Pharma USA, Inc.CompletedInherited Mitochondrial Disease, Including Leigh SyndromeUnited States
-
Chiesi SA/NVEnrolling by invitationNephropathic CystinosisBelgium
-
FDA Office of Orphan Products DevelopmentLeadiant Biosciences, Inc.Completed
-
Hospices Civils de LyonCompleted
-
Augusta UniversityTerminatedSchizophrenia | SchizoaffectiveUnited States
-
University of California, San DiegoRaptor Pharmaceuticals Corp.CompletedCystinosis | Nephropathic CystinosisUnited States
-
UnionDermSkin of Color Society; Solta Medical; ScientisRecruiting
-
Horizon Pharma USA, Inc.CompletedCystinosisFrance, United States, United Kingdom, Belgium, Italy, Netherlands