To evaluate the long-term safety, tolerability and efficacy of ArikaceTM 590 mg for a maximum 12 cycles administered once daily, where each cycle consists of 28 days on treatment followed by 28 days off treatment.
ID
Source
Brief title
Condition
- Respiratory disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints
• Adverse events (AE) as a result of treatment up to Day 672
• Adverse events leading to study medicine being permanently discontinued
• Severe adverse events (SAEs) up to Day 672
• Laboratory abnormalities up to Day 672
• Acute tolerability as measured by PFT changes pre to post dose
• Vital signs and oxygen saturation (changes from pre- to post dose) and change
from baseline
• Shift in MICs for Pa and Burkholderia sp from Day 1 to Days 169, 337, 505 and
672
• Proportion of subjects with emergent pathogens
• Evaluation of audiology
• Change in serum creatinine throughout the entire study
• Concomitant medication including antibiotics, anti-viral agents, antifungal
agents and other inhalation medicines, such as bronchodilators, DNase, inhaled
steroids
Secondary outcome
Secondary endpoints
• Relative change in FEV1 [litres] and FEV1 (% predicted) during the study
• Time to the first protocol defined pulmonary exacerbation and proportion of
subjects experiencing a protocol defined pulmonary exacerbation
• Time to first treatment with anti-pseudomonal antibiotics for each
protocol-defined pulmonary exacerbation, proportion of subjects initiating
treatment and number of treatment days
Exploratory endpoints
• Time to the first pulmonary exacerbation as defined by the investigator and
proportion of subjects experiencing a pulmonary exacerbation as defined by the
investigator
• Time to first pulmonary exacerbation defined by the Seattle Score (Rosenfeld
Criteria) and proportion of subjects experiencing a pulmonary exacerbation
defined by the Seattle Score Time to first treatment with anti-pseudomonal
antibiotics for each pulmonary exacerbation (protocol-defined or
investigator-defined), proportion of subjects initiating treatment and number
of treatment days.
• Log CFU Pa and change in log CFU Pa from baseline during the entire study
• Log CFU Burkholderia species and change in log CFU Burkholderia species from
baseline throughout the entire study
• Time to, number and duration of hospital admissions and proportions of
subjects admitted to hospital irrespective of the reason
• Time to, number and duration of hospital admissions and proportions of
subjects admitted to hospital for pulmonary exacerbation
• Change in patient-reported symptoms from baseline during the entire study as
measured by the Cystic Fibrosis respiratory symptom diary (CFRSD) (the
instrument is only available in English and therefore will only be completed in
English speaking countries by subjects who do not have any problems reading and
speaking English)
• Change in respiratory symptoms from baseline during the entire study as
measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
• Evaluation of the global rating of health at each study visit and change from
baseline throughout the study
• Proportion of subjects reporting work or school days missed as a result of
underlying CF complications and the number of days missed
• FEV1 (litres) and FEV1 (% predicted) and absolute change in FEV1 (litres) and
FEV1 (% predicted) during the entire study; forced vital capacity (FVC) and
forced expiratory flow (FEF(25-75%)) during the entire study and absolute
change in and relative change in FVC and FEF(25-75%) during the entire study
• Evaluation time to and frequency of pulmonary exacerbations, relative change
in FEV1 (volume) and FEV1 % predicted, time to anti-pseudomonal rescue
treatment, log CFU change, change in CFQR-Respiratory domain, change in CFRSD
and change in GRH through FEV1 % predicted, age and additional subgroups.
Background summary
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Study objective
To evaluate the long-term safety, tolerability and efficacy of ArikaceTM 590 mg
for a maximum 12 cycles administered once daily, where each cycle consists of
28 days on treatment followed by 28 days off treatment.
Study design
This is a Phase 3 trial into the long-term safety, tolerability and efficacy of
590 mg ArikaceTM.
All subjects who have completed study TR02-108 or TR02-109 were compliant with
the study protocol and did not satisfy the criteria for discontinuing the
trial, will participate in this open-label trial. The subjects will receive a
single daily dose of 590 mg ArikaceTM for 28 days via a PARI investigational
eFlow® nebuliser system (eFlow®), followed by a treatment period of 28 days
with no treatment. This cycle (28 days on treatment, 28 days off treatment)
will be repeated for a maximum 12 cycles. The study will be implemented as two
successive extension periods, each consisting of 48 weeks (approximately 12
months). After completing the first extension period the subjects will be asked
to provide their consent again for the second follow-up. The total length of
the trial will be a maximum of 96 weeks (approximately 2 years).
During the first 28 days of treatment the subjects will be evaluated every two
weeks at the study site for safety, tolerability and efficacy. After this the
subjects will be evaluated on the first and last day of each treatment period
at the study site for the duration of the study. During the study, starting at
the off treatment period for cycle 1, there will be a single telephone contact
during each 28 day period with the subject to evaluate safety. A last visit to
the site will take place 28 days after the last dose of ArikaceTM.
Clinical laboratory parameters, adverse events, concomitant medicines, vital
signs, physical examinations, audiology, lung function and patient reported
symptoms/results will be evaluated for all study subjects during the study.
Sputum samples will be taken in order to determine changes in bacterial
density, pathogens identified and MICs.
Intervention
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Study burden and risks
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Schipholweg 103
Leiden 2316 XC
NL
Schipholweg 103
Leiden 2316 XC
NL
Listed location countries
Age
Inclusion criteria
1) Written informed consent or assent obtained from the subject, parent or legal guardian to participate in the open label multi-cycle study, TR02-110
2) Subject has completed study TR02-108 or TR02-109, and has been compliant with the study protocol
3) Negative pregnancy result on pregnancy test performed within 2 weeks prior to Day 1 and use of reliable methods of contraception (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD) throughout the study duration in women of child-bearing potential. Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile
Exclusion criteria
1) Subject met any of the listed criteria for study drug discontinuation (safety reasons or non-compliance) in protocol TR02-108 or TR02-109
2) Elevated AST, ALT or GGT >= 3× the upper limit of normal (ULN) within 4 weeks prior to Day 1
3) Absolute neutrophil count < 1000 within 4 weeks prior to Day 1
4) Serum creatinine > 2× ULN within 4 weeks prior to Day 1
5) Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
6) History of alcohol, medication, or illicit drug abuse within the 6 months prior to consent
7) Smoking tobacco or any substance within 6 months prior to consent or anticipated inability to refrain from smoking throughout the study
8) Any condition which in the opinion of the investigator interferes with the subject*s ability to safely complete the study or adhere to the study requirements
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 | EUCTR2011-000443-24-NL |
| ClinicalTrials.gov | NCT001316276 |
| CCMO | NL37137.041.11 |