NCT03774290

Study to Investigate the Effect of PBF-680 on Forced Expiratory Volume in 1 Second (FEV1) in Asthmatic Patients

A Phase II, Double-blind, Randomized, Parallel-group, Placebo- Controlled Multi-center Study to Investigate the Effect of the Adenosine A1 Receptor Antagonist PBF-680 on Forced Expiratory Volume in 1 Second (FEV1) in Patients With Mild-to-moderate Persistent Atopic Asthma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 107 (actual)
• Sponsor: Palobiofarma SL · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Asthma

Interventions

Type	Name	Description
DRUG	PBF-680	PBF-680 is an adenosine A1 receptor antagonist
DRUG	Placebo oral capsule	Oral gelatine capsule

Timeline

• Start date: 2018-06-01
• Primary completion: 2020-02-05
• Completion: 2020-03-16
• First posted: 2018-12-12
• Last updated: 2020-09-25

Locations

1 site across 1 country: Spain