First Study of Oral Cysteamine in Cystic Fibrosis

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Cysteamine	Phase 1; Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Official Title:	An Open Label Investigation of the Tolerability and Pharmacokinetics of Oral Cysteamine in Adults With Cystic Fibrosis.
Study Start Date :	August 2014
Actual Primary Completion Date :	March 2015
Actual Study Completion Date :	April 2015

Arms and Interventions

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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	Drug: Cysteamine; 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 Name: Cystagon 150mg capsules

Outcome Measures

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Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Concentration of cysteamine in sputum at week 5 [ Time Frame: 3 hours after final dose ]

Other Outcome Measures:

1. Change in weight from baseline at week 5 [ Time Frame: 5 weeks ]
2. Number of Participants with Serious and Non-Serious Adverse Events [ Time Frame: 6 weeks ]
3. Change in FEV1, FVC from baseline at week 5 [ Time Frame: 5 weeks ]
4. Change in disease related health status from baseline at week 5 measured by CFQ-R [ Time Frame: 5 weeks ]
5. Change in haematological and biochemical indices from baseline at week 5 [ Time Frame: 5 weeks ]
6. change in sputum microbiology from baseline at week 5 [ Time Frame: 5 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Locations

United Kingdom
Aberdeen Royal Infirmary
Aberdeen, United Kingdom, AB25 2ZN

Sponsors and Collaborators

University of Aberdeen

Cystic Fibrosis Trust

NHS Grampian

University of Huddersfield

Investigators

Principal Investigator:	Graham Devereux, MD	University of Aberdeen

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	University of Aberdeen
ClinicalTrials.gov Identifier:	NCT02212431 History of Changes
Other Study ID Numbers:	3/001/14; 2014-000284-40 ( EudraCT Number )
First Posted:	August 8, 2014
Last Update Posted:	November 5, 2015
Last Verified:	November 2015

Keywords provided by University of Aberdeen:

Cystic Fibrosis; Cysteamine; Pharmacokinetics

Additional relevant MeSH terms:

Fibrosis; Cystic Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases	Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Cysteamine; Cystine Depleting Agents; Molecular Mechanisms of Pharmacological Action