to investigate the safety and tolerability of pirfenidone in asbestosis patients
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective is to investigate the safety and tolerability of
pirfenidone in asbestosis patients as measured by weekly digital symptom and AE
score
Secondary outcome
Secondary objective is describing the effect of pirfenidone, as measured by
daily home spirometry, in-hospital pulmonary function (spirometry and diffusion
capacity), 6-minute walking test and patient reported outcomes as measured by
King*s Brief Interstitial Lung disease Questionnaire (K-BILD) and Leicester
Cough Questionnaire (LCQ).
Background summary
Recently, antifibrotic therapy has been approved for the treatment of
idiopathic pulmonary fibrosis (IPF), a progressive fibrotic lung disease.
Pirfenidone is an antifibrotic agent with anti-inflammatory properties that has
been shown to reduce disease progression significantly, as measured by changes
in forced vital capacity (FVC). The tolerability and effect of pirfenidone on
other fibrosing lung diseases like asbestosis is not clear yet. Asbestosis is
a rare and progressive pneumoconiosis, caused by inhalation of asbestos fibers.
The disease course is variable but characterized by progressive fibrosis.
Sometimes, disease appearance and disease course are hard to distinguish from
idiopathic lung fibrosis (IPF). There is currently no specific treatment for
asbestosis, except preventive and supportive measures like smoking cessation
and supplemental oxygen when needed.
Study objective
to investigate the safety and tolerability of pirfenidone in asbestosis
patients
Study design
This is a prospective, multicenter descriptive safety study
Intervention
the patients receive treatment with pirfenidone 3 times daily 801mg during 24
weeks
Study burden and risks
The patients are asked to perform a home monitoring program with real-time
wireless home spirometry and weekly symptom and AE score to assess safety and
tolerability. A recent pilot study in IPF showed that the majority of patients
considered daily spirometry easy (80%) and not burdensome at all (90%), the
other patients were neutral. All patients considered real-time spirometry
useful and would recommend it to others, 90% wished to continue home monitoring
after the pilot.
amount and number of blood samples: 7x (at inclusion, and 6x monthly during
treatment)
number of site visits & physical examinations 4X (at inclusion, week 0, 12 and
24 of treatment)
number of pulmonary function test: 4X (at inclusion, week 0, 12 and 24 of
treatment)
number of 6 minute walking tests: 4x (at inclusion, week 0, 12 and 24 of
treatment)
number of questionnaire: 4X (at inclusion, week 0, 12 and 24 of treatment)
King*s Brief Interstitial Lung disease Questionnaire (K-BILD) and Leicester
Cough Questionnaire (LCQ).
risks associated with the investigational treatment: summary of the safety
profile of Pirfenidone from CPC text.
The most frequently reported adverse reactions during clinical study experience
with pirfenidone at a dose of 2,403 mg/day compared to placebo, respectively,
were nausea (32.4% versus 12.2%), rash (26.2% versus 7.7%), diarrhoea (18.8%
versus 14.4%), fatigue (18.5% versus 10.4%), dyspepsia (16.1% versus 5.0%),
anorexia (11.4% versus 3.5%), headache (10.1% versus 7.7%), and
photosensitivity reaction (9.3% versus 1.1%).
Tabulated list of adverse reactions
The safety of pirfenidone has been evaluated in clinical studies including
1,650 volunteers and patients. Pirfenidone has been investigated in open
studies for more than five years and some for up to 10 years.
Luijbenstraat 15
's-Hertogenbosch 5211BR
NL
Luijbenstraat 15
's-Hertogenbosch 5211BR
NL
Listed location countries
Age
Inclusion criteria
Patients (40-85 years) with confirmed asbestosis by Dutch NVALT IPF expertise-panel (History of asbestos exposition with 15-30 years latency ;AND pleural plaques OR asbestos fibers in pulmonary lavage OR asbestos fibers confirmed in lung biopsy), AND criteria 1-6 ;1. written informed consent
2. FVC * 50% predicted, DLCO * 25%
3. Minimal 6 minute walk test distance 150 meter
4. FEV1/FVC > 0.70
5. Documented disease progression in 3-6 months (absolute of relative FVC decrease 5% in 3-6 months or absolute or relative DLCOc decrease > 10% in 3-6 months, or decrease * 25 meter on 6 minute walk test in 3-6 months)
Exclusion criteria
1. current smoker
2. > 15% emphysema on HRCT thorax
3. >10mg prednisone daily or other immunosuppressant (MTX, azathioprine, cyclophosphamide)
4. malignancy
5. Hepatic impairment (History of hepatic impairment, elevation of transaminase enzymes, or the confirmation of any of the following liver function test criteria above the specified limits: Total bilirubin above the upper limit of normal (ULN), Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × ULN, Alkaline phosphatase > 2.0 × ULN)
6. Renal impairment (GFR < 30 ml/min or dialysis)
7.Pregnancy
8.Concomitant use of a strong and selective inhibitor of CYP1A2 (Fluvoxamin, enoxacin)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-001781-41-NL |
| CCMO | NL61183.078.18 |