* To assess the safety and tolerability of inhaled PA101 delivered via eFlow in patients with IPF with refractory chronic cough.* To assess the efficacy potential of inhaled PA101 by measuring the changes in cough severity and the urge-to-cough as…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The efficacy variables for this study will be:
* Change from pre-dose Day 1 to pre-dose Day 4 in 24-hour cough severity
measured by VAS scale
* Change from pre-dose Day 1 to pre-dose Day 4 in urge-to-cough measured by VAS
scale
* Change in total cough count measured by LCM from the first 24 hours of
monitoring to the last 24 hours of monitoring
Safety outcome variables for this study will include AEs and changes from
baseline in the following parameters:
* Change from pre- to post-dose in vital signs (i.e., systolic/diastolic blood
pressure, heart rate) on Days 1 and 4
* Change from pre- to post-dose in 12-lead ECG parameters (including QTc) on
Days 1 and 4
* Change in PFTs (i.e., FEV1, FVC and FEV1/FVC ratio) from pre-dose on Day 1 to
post-dose on Day 4
Secondary outcome
Not applicable
Background summary
Patara Pharma, LLC is developing a new inhalation formulation of cromolyn
sodium (PA101) delivered via the eFlow® high efficiency nebulizer system (PARI
GmbH, Germany). PA101 is a novel inhalation solution formulation of cromolyn
sodium having osmolality and pH adjusted to a physiologically well tolerable
range. PA101 is preservative free, room temperature-stable formulation
optimized for improved tolerability via oral inhalation and long-term chemical
stability. The eFlow nebulizer is a portable, handheld, silent,
high-efficiency nebulizer with rapid delivery that can deliver a dose in less
than 3 minutes. A recently completed study in healthy subjects, patients with
allergic asthma and patients with systemic mastocytosis demonstrated that PA101
is safe and well tolerated, and delivering PA101 with the eFlow nebulizer
system (*Cromoflow*) achieves higher lung deposition and systemic levels of
cromolyn sodium relative to currently marketed inhalation and oral formulations
of cromolyn sodium (Clinical Study Report PA101-01).
Study objective
* To assess the safety and tolerability of inhaled PA101 delivered via eFlow in
patients with IPF with refractory chronic cough.
* To assess the efficacy potential of inhaled PA101 by measuring the changes in
cough severity and the urge-to-cough as measured by Visual Analog Scale (VAS)
and the change in 24-hour cough count measured by Leicester Cough Monitor
(LCM).
Study design
This is a Phase 1b, randomized, double-blind, single-center, 3-period crossover
study conducted in 6 patients of 40-79 years of age with idiopathic pulmonary
fibrosis (IPF) with refractory chronic cough. In each Treatment Period,
patients will receive one of three treatments: PA101, Placebo A or Placebo B.
Intervention
During the Screening Visit, the patients will first receive an explanation of
the purpose and nature of the study and sign the consent form. The following
procedures will then be performed:
* Determine eligibility according to the inclusion/exclusion criteria
* Obtain patient*s medical history
* Perform physical examination including height, weight and BMI
* Perform urine pregnancy test (females of child-bearing potential only)
* Record vital signs (i.e., systolic and diastolic blood pressure, heart rate)
and 12-lead ECG
* Perform alcohol breath or urine test
* Perform urine testing for drugs of abuse
* Review and record concomitant medications taken within the last 14 days.
In each treatment period, the patients will visit the clinic in the morning to
receive the first dose on Day 1 (Visit 1) and the last dose on Day 4 (Visit 2);
the other doses will be self-administered by the patients. A self-recorded
daily diary will be used to record dosing information in each treatment period.
The safety assessments (AEs, vital signs and 12-lead ECG), pulmonary function
testing (FEV1, FVC, and FEV1/FVC ratio), and the cough severity and the
urge-to-cough assessments using VAS scale will be performed in the morning
during clinic visits on Day 1 and Day 4 in each Treatment Period. In addition,
a cough count device (LCM) will be dispensed in the morning on Day 1 for
continuous measurement of cough count for the duration of each Treatment Period.
A safety follow-up call will be placed within 5 days (± 2 days) following the
last study treatment.
Study burden and risks
This study may produce the following most commonly reported side effects (at
least 2 patients/subjects): cough, shortness of breath, tickle in the throat,
dizziness, headache, change in taste.
Less common reported side effects (one patient/subject) include nasal
congestion, nausea, sneezing, wheezing, diarrhoea, itching, muscle pain,
abdominal pain, rash, irritability, fatigue
In very rare cases a generalised allergic reaction may occur, the first time
the study medication is inhaled. In some cases, inhaled PA101 may create a
narrowing of the airways.
The knowledge about potential side effects increases with every study.
Patients may not benefit directly from participating, but this study might
deliver data that helps development of medication for IPF patients
High Bluff Drive 12670
San Diego 92130
US
High Bluff Drive 12670
San Diego 92130
US
Listed location countries
Age
Inclusion criteria
1. Male or female patients age 40 through 79 years, inclusive;2. Diagnosis of Idiopathic Pulmonary Fibrosis with the consensus of the multidisciplinary team based on the presence of definitive or possible usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) and after excluding alternative diagnoses, including lung diseases associated with environmental and occupational exposure, with connective tissue diseases and with drugs ;3. Chronic cough present for at least 8 weeks and not responsive to current therapies ;4. Daytime cough severity score on visual analogue scale >40 mm at the Screening Visit;5. Transfer capacity for carbon monoxide corrected for hemoglobin (TLCOc) >25% predicted value within 3 months and Forced Vital Capacity (FVC) >50% predicted value within 1 month of the Screening Visit
Exclusion criteria
1. Current or recent history of clinically significant medical condition, laboratory abnormality, or illness that could put the patient at risk or compromise the quality of the study data as determined by the investigator;2. Significant cardiac disease (i.e., myocardial infarction within 6 months or unstable angina within 1 month of the Screening Visit);3. An upper or lower respiratory tract infection within 4 weeks of the Screening Visit;4. Acute exacerbation of IPF within 3 months of the Screening Visit;5. Long-term daily oxygen therapy (>10 hours/day) ;6. Presence of pulmonary arterial hypertension with limitation of activity;11. Use of the following drugs within 2 weeks prior to the Screening Visit: Prednisone, narcotic antitussives, baclofen, gabapentin, and inhaled corticosteroids
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 | EUCTR2014-005180-32-NL |
| CCMO | NL51634.056.14 |