This study is the second Phase-II trial analyzing efficacy outcomes of PBF-680 in asthmatic subjects, following the supportive data from the proof-of-concept trial on the effect of PBF-680 on airway hyperresponsiveness to adenosine monophasphate (AMP). The purpose of the present study is to provide an assessment on the efficacy of a 5-day treatment course of once daily, orally administered, 10-mg PBF-680 doses, to attenuate "Late Asthmatic Responses" (LAR) as a primary efficacy outcome. The study also aims at analyzing the effect of the PBF-680 treatment course on airway inflammation-related outcomes including airway hyperresponsiveness to AMP at 24 h after allergen bronchoprovocation, plus nitric oxide fraction in exhaled air (FeNO) and airway inflammatory cells counts in induced sputum under the effect of an additional 10-mg PBF-680 dose on the 6th treatment period day. Overall, the study aims at providing evidence on the efficacy of PBF-680 on outcomes, particularly the LAR, that are well established to screen valid drugs for asthma maintenance therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
8
Unitat de Pneumologia Experimental
Barcelona, Spain
Late Asthmatic Response (LAR) , measured as the fall of the forced expiratory volume (FEV1) between 3 and 10 hours postallergen bronchoprovocation
Time frame: 3-to-10 hour post-allergen bronchoprovocation.
Early Asthmatic Response (EAR), measured as the maximum FEV1 fall from the postdiluent value
Time frame: within 1 hour post-allergen bronchoprovocation.
hyperresponsiveness to AMP in terms of provocative concentration causing a 20% fall (PC20) increment in response to AMP airway challenge
Time frame: 24-hour post-allergen bronchoprovocation
Nitric oxide fraction in exhaled air (FeNO) on post-allergen bronchoprovocation day
Time frame: 6th treatment period day
Total leukocytes per mL in induced sputum on post-allergen bronchoprovocation day
Time frame: 6th treatment period day
Leukocyte differential counts per mL in induced sputum on post-allergen bronchoprovocation day.
Leukocyte subpopulations from cytocentrifuged, stained preparations will be counted and expressed as percentage cell numbers per volume unit.
Time frame: 6th treatment period day
Adverse events
The occurrence of adverse events will be monitored through the complete study. Adverse events will be recorded with the following information: severity grade (mild, moderate, severe); suspected/unsuspected relationship to the study drug; duration (date and time of onset, defined as precisely as possible, and end date or if continuing at final exam)
Time frame: 2 Months
Vital signs
Vital signs will include radial artery pulse rate (measured for 60 seconds), and systolic and diastolic blood pressure. Pulse rate and blood pressure will be assessed in the right arm after the patient has rested in the sitting position for at least 5 min. Vital sign values will be recorded as notable if: pulse rate \<40 or \>90 bpm; systolic blood pressure \<90 or \>140 mmHg; diastolic blood pressure \<50 or \>90 mmHg.
Time frame: 9 times during 2 months
Number of Participants With Abnormal Laboratory Values
On visits V2+24h, V4+24h and V6+24h, venipuncture will be performed for blood laboratory evaluations. The analysis will be performed at the local laboratory, and will include: hemogram with complete blood counts and differential leukocyte counts; clinical biochemistry including electrolytes (sodium, potassium, chloride), glucose, creatinine, urea, aspartate transaminase (AST), alanine transaminase (ALT), gammaglutamyl transpeptidase (GGT) and bilirubin; and serum immunoglobulin E (IgE) (only on visit V2+24h).
Time frame: 4 times during 2 months
Physical examination
Time frame: 7 times during 2 months
Electrocardiogram (EKG)
Time frame: 3 times during 2 months
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