Evaluation of Pharmacokinetics, Relative Bioavailability, and Tolerability of Three Different Formulations of PA101 in Healthy Subjects, Patients with Systemic Mastocytosis, and Patients with Chronic Cough due to Idiopathic Pulmonary Fibrosis

Completed

Conditions: aandoeningen gerelateerd aan de mast cellen (mastocyten)
Systemic Mastocytosis and inflammatory
10001708

Registration Number: NL-OMON42687

Lead Sponsor: PATARA PHARMA, LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 24

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)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Pharmacokinetic measurements: The PK parameters to be evaluated for plasma<br /><br>DSCG are maximum concentration (Cmax), time to maximum concentration (Tmax),<br /><br>terminal elimination half-life (T1/2), area under the plasma concentration-time<br /><br>curve from time = 0 to time of last measurable drug concentration (AUC0-t), and<br /><br>area under the plasma concentration-time curve from time = 0 to infinity<br /><br>(AUC0-inf). Urine DSCG levels will be measured for total DSCG excretion in the<br /><br>urine.<br /><br>Safety measurements: Adverse events, changes in vital signs and 12-lead ECG. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Biomarker sample will be analyzed for potential predictive biomarkers as an<br /><br>exploratory analysis. The biomarkers tested will include the following:<br /><br>• Cytokines (IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, among others)<br /><br>• Chemokines (CCL22, CCL3, CCL5, CXCL7, among others)<br /><br>• Eicosanoids (PGD2, PGE1, PGE2, LTB4, LTC4, LTD4, LTE2, among others)<br /><br>• Other mediators (tryptase, chymase, serotonin, among others)<br /><br>• MicroRNA profile</p><br>