Study to Investigate the Effect of PBF-680 on Forced Expiratory Volume in 1 Second (FEV1) in Asthmatic Patients
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2

Summary: 
      The present trial is an exploratory study aiming at evaluating the safety, tolerability, and
      efficacy of a 15-day, once daily administration of 10 mg PBF-680 in subjects with persistent,
      mild-to-moderate atopic asthma.
    

Detailed description: 
      Purpose and rationale: Extracellular adenosine, produced from dephosphorylation of adenosine
      triphosphate (ATP) and adenosine monophasphate (AMP), is an important signaling molecule in
      asthma, involved in bronchoconstriction and airway inflammation. PBF-680 is an A1 adenosine
      receptor antagonist that has successfully completed single dose escalation and
      treatment-period phase-I trials in healthy volunteers, plus a crossover, proof-of-concept
      Phase-IIa trial in mild and moderate asthmatics, where a single dose significantly attenuated
      airway hyperresponsiveness to AMP challenge and increased 8-hour post-challenge FEV1. In
      terms of exploratory efficacy, the primary purpose of this study is to determine whether
      PBF-680 compared to placebo, improves the FEV1, as well as to provide comparative safety data
      from this population of asthmatics. Measurements made in this study will also be used to
      establish whether this treatment improves other variables related to asthma control and lung
      function.

      Objectives: The primary objective is to demonstrate an improvement in trough FEV1 upon a
      15-day treatment with PBF-680 compared to placebo in mild-to-moderate asthmatics that, on
      study entry, are managed in Global Initiative for Asthma (GINA) therapeutic steps 2-3.
      Secondary objectives include determinations of FEV1 area under the curve (AUC), evaluations
      on pre- and post- bronchodilator FEV1, and patient reported outcomes (PROs) including Asthma
      Control Questionnaire-7 (ACQ-7) and Standardized Asthma Quality of Life Questionnaire
      (AQLQ(S)).

      Study design and population: this is a multicenter, double-blind, randomized, placebo-
      controlled trial with a 2-arm parallel design. The treatments studied are once-daily PBF- 680
      10 mg and placebo, as two orally administered, 5-mg PBF-680 capsules or two placebo capsules,
      respectively. The study comprises: (i) a minimum of 5-days screening period, during which,
      the subject's clinical stability and overall eligibility for the study will be assessed; (ii)
      a weaning phase where a stepwise tapering of the asthma medication will be done upon 7-day
      periods; (iii) the randomized, parallel-arm treatment period; and (iv) an end-of-study
      follow-up visit. The asthma medication weaning period comprises three possible visit pathways
      in order to adjust for each subject's asthma therapy on study entry. The study will comprise
      a primary analysis population of 58 stable asthmatic subjects managed as described for the
      objectives, who meet all inclusion criteria and no exclusion criteria and complete a full,
      valid data set for the primary variable. The total recruitment estimates to meet this target
      is 78 subjects.
    

Intervention name(s): PBF-680; Placebo oral capsule
Intervention type(s): Drug; Drug
Intervention description(s): PBF-680 is an adenosine A1 receptor antagonist; Oral gelatine capsule
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment