First Study of Oral Cysteamine in Cystic Fibrosis

NCT02212431 | Completed Phase 1 DMC

• 2 other identifiers: 3/001/142014-000284-40
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Cysteamine; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Elimination rate constant [k]

  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 Outcomes (1)

• Concentration of cysteamine in sputum at week 5

  3 hours after final dose

Other Outcomes (6)

• Change in weight from baseline at week 5

  5 weeks

• Number of Participants with Serious and Non-Serious Adverse Events

  6 weeks

• Change in FEV1, FVC from baseline at week 5

  5 weeks

Study Arms (1)

Cysteamine

EXPERIMENTAL

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

Interventions

Cysteamine DRUG

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

Also known as: Cystagon 150mg capsules

Cysteamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Aberdeen: lead
• Cystic Fibrosis Trust: collaborator
• NHS Grampian: collaborator
• University of Huddersfield: collaborator

Study Sites (1)

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Cysteamine

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Mercaptoethylamines; Ethylamines; Amines; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds

Study Officials

• Graham Devereux, MD

  University of Aberdeen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 8, 2014
• Study Start: August 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: April 1, 2015
• Last Updated: November 5, 2015

Record last verified: 2015-11

Locations

GB (1)