The objectives of the study are as follows:Primary:• Part 1: To assess the pharmacokinetics and relative bioavailability of three different formulations of PA101 (4% cromolyn sodium with and without mannitol, and 6% cromolyn sodium without mannitol…
ID
Source
Brief title
Condition
- Other condition
- Allergic conditions
Synonym
Health condition
aandoeningen gerelateerd aan de mast cellen (mastocyten)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic measurements: The PK parameters to be evaluated for plasma
DSCG are maximum concentration (Cmax), time to maximum concentration (Tmax),
terminal elimination half-life (T1/2), area under the plasma concentration-time
curve from time = 0 to time of last measurable drug concentration (AUC0-t), and
area under the plasma concentration-time curve from time = 0 to infinity
(AUC0-inf). Urine DSCG levels will be measured for total DSCG excretion in the
urine.
Safety measurements: Adverse events, changes in vital signs and 12-lead ECG.
Secondary outcome
Biomarker sample will be analyzed for potential predictive biomarkers as an
exploratory analysis. The biomarkers tested will include the following:
• Cytokines (IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, among others)
• Chemokines (CCL22, CCL3, CCL5, CXCL7, among others)
• Eicosanoids (PGD2, PGE1, PGE2, LTB4, LTC4, LTD4, LTE2, among others)
• Other mediators (tryptase, chymase, serotonin, among others)
• MicroRNA profile
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 preservative-free, room temperature-stable formulation
with optimized pH and osmolality 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. Delivering PA101 with the eFlow nebulizer system
(*Cromoflow*) achieves higher lung deposition and systemic levels of cromolyn
sodium relative to currently marketed formulations of cromolyn sodium.
PA101 is being investigated as a first-line maintenance therapy for the
treatment of clinical symptoms related to systemic mastocytosis, chronic cough
related to idiopathic pulmonary fibrosis, and other mast cell associated
disorders. Currently, PA101 is being tested in Phase 2 clinical trials in
Europe in patients with ISM and in patients with refractory chronic cough in
IPF and chronic idiopathic cough.
Study objective
The objectives of the study are as follows:
Primary:
• Part 1: To assess the pharmacokinetics and relative bioavailability of three
different formulations of PA101 (4% cromolyn sodium with and without mannitol,
and 6% cromolyn sodium without mannitol) in healthy adult volunteers.
• Parts 2 and 3: To assess the pharmacokinetics and relative bioavailability of
two different formulations of PA101 (4% cromolyn sodium with and without
mannitol) in patients with indolent systemic mastocytosis and patients with
chronic cough due to idiopathic pulmonary fibrosis.
Secondary:
• To assess the safety and tolerability of three different formulations of
PA101 using AEs, vital signs and ECGs.
• To assess biomarkers prior to and following PA101 administration.
Study design
This is a Phase 1, randomized, double-blind, crossover study conducted in three
parts: Part 1 will be a 4-period crossover study conducted in 12 healthy adult
subjects; Part 2 will be a 3-period crossover study in 6 patients with indolent
systemic mastocytosis (ISM); and Part 3 will be a 3-period crossover study in 6
patients with chronic cough due to idiopathic pulmonary fibrosis (IPF). Part 1
will be completed first followed by Parts 2 and 3 after the analysis of data
from Part 1.
Intervention
The study will start with a screening visit. During the screening visit
standard medical assessments including safety laboratory tests (blood draw,
urine collection), an alcohol breath test, urine drug screen, a physical
examination, ECG and a vital signs measurement will be performed.
After the subject passes all above mentioned tests, the subject will be
enrolled in the medication phase. During study the subjects will enter the
clinic, will receive 2 or 3 medication formulations and placebo during 3 or 4
periods. They will be asked on a regular basis for possible side effects, blood
will be drawn for safety and PK measurements and the vital signs will be
checked regularly during the confinement periods. .
Finally a follow-up phone call will be performed. During this call the subjects
will be asked for possible side effects.
Study burden and risks
There were no serious AEs, and most AEs were mild in intensity. The most common
AEs were cough, dyspnea, throat irritation, dizziness, headache, and dysgeusia.
11455 El Camino Real Suite 460
San Diego, California CA 92130
US
11455 El Camino Real Suite 460
San Diego, California CA 92130
US
Listed location countries
Age
Inclusion criteria
Part 1: Healthy Subjects
1. Male or female subjects 18-45 years of age, inclusive
2. Body weight > 50 kg and Body Mass Index of 18-25 kg/m2, inclusive
3. Normal 12-lead ECG recording at the Screening Visit
4. Normal or clinically insignificant changes in 12-lead ECG recording at the Screening Visit
Part 2:
1. Male or female subjects 18-65 years of age, inclusive
2. Diagnosed with indolent systemic mastocytosis (ISM) according to the WHO criteria
3. History of gastrointestinal symptoms related to systemic mastocytosis
4. Clinically stable systemic mastocytosis
5. Normal lung function (FEV1 >= 90% of predicted normal value) at the Screening Visit;Part 3:
1. Male or female patients age 40 through 75 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 and Forced Vital Capacity (FVC) > 50% predicted value within 3 months of the Screening Visit
Exclusion criteria
Part 1:
1. Current or recent history of clinically significant cardiovascular, respiratory, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant or other illnesses that could put the subject at risk or compromise the quality of the study data as determined by the investigator
2. An upper or lower respiratory tract infection within 4 weeks
Part 2:
1. Aggressive systemic mastocytosis, mast cell leukemia, or systemic mastocytosis with an associated clonal hematologic non-mast cell disorder
2. Current or recent history of clinically significant cardiovascular, respiratory, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant or other illnesses that could put the subject at risk or compromise the quality of the study data as determined by the investigator
3. History of systemic corticosteroid use within 6 weeks or immunosuppressive therapy within 6 months of the Screening Visit
Part 3:
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)
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 | EUCTR2015-003375-30-NL |
| CCMO | NL54835.056.15 |