Study to Investigate the Effect of PBF-680 on Forced Expiratory Volume in 1 Second (FEV1) in Asthmatic Patients (ADENOASMA)
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|ClinicalTrials.gov Identifier: NCT03774290|
Recruitment Status : Completed
First Posted : December 12, 2018
Last Update Posted : September 25, 2020
|Condition or disease||Intervention/treatment||Phase|
|Asthma||Drug: PBF-680 Drug: Placebo oral capsule||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||107 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||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|
|Actual Study Start Date :||June 1, 2018|
|Actual Primary Completion Date :||February 5, 2020|
|Actual Study Completion Date :||March 16, 2020|
Experimental: PBF-680 10 mg
10 mg of PBF-680 once a day
PBF-680 is an adenosine A1 receptor antagonist
Placebo Comparator: Placebo oral capsules
Placebo once a day
Drug: Placebo oral capsule
Oral gelatine capsule
- Effect of PBF-680 on trough forced expiratory volume in 1 second (FEV1) [ Time Frame: 16 Days ]Defined as the average of the FEV1 measurements taken at 23h 15min and 23h 45min post-dose after the final dose.
- Effect of PBF-680 in the FEV1 area under curve AUC30min-23h 30min post-dose [ Time Frame: 16 days ]Defined as the FEV1 area under curve of a serial of spirometries from 30min-23h 30min post-dose through days 15-to-16
- Effect of PBF-680 in the standardized FEV1 AUC30min-6h post- dose [ Time Frame: 15 Days ]Defined as the FEV1 area under curve of a serial of spirometries from 30min-6h post-dose on day 15
- Effect of PBF-680 in the pre-bronchodilator FEV1 [ Time Frame: 8 days ]Defined as the FEV1 before use of bronchodilator at pre-dose spirometry on day 8
- Effect of PBF-680 in the post- bronchodilator FEV1 at pre-dose spirometry on day 8 [ Time Frame: Day 8 and Day 16 ]Defined as the FEV1 after use of bronchodilator at pre-dose spirometry on day 8 and 16
- Effect of PBF-680 on the asthma control as measured by Asthma Questionnaires [ Time Frame: Day 8 and Day 15 ]
Asthma Control Questionnaire (ACQ-7) comprises 5 patient-reported symptoms that are scored from 0 to 6.The points are added and divided by 5. According to the result:
Less than or equal to 0.75: Adequate control of asthma From 0.75 to 1.50: partially controlled asthma More than 1.50: Inadequate control of asthma. The Asthma Quality of Life Questionnaire AQLQ(S) scores symptoms, activity limitation, emotional function, and environmental exposure through 32 questions. The overall AQLQ score is the mean of the responses to each-of the 32 questions on a 7- point scale (7=no impairment, 1 =severe impairment)
- Effect of PBF-680 on daily, morning and evening FEV1 and PEF as measured by an electronic diary/Peak Expiratory Flow (PEF) meter device. [ Time Frame: 16 days ]On each morning and evening, the subjects must ﬁll the diary questions and record three brief expiratory maneuvers that generate PEF and FEV1 data.
- Effect of PBF-680 in the use of rescue bronchodilator as reported by the subject using an electronic diary/PEF meter device. [ Time Frame: 16 days ]On each morning and evening, the subjects must ﬁll the diary questions and record three brief expiratory maneuvers that generate PEF and FEV1 data
- Number of subjects with treatment-related adverse events as assessed by CTCAE v4 [ Time Frame: 16 days ]Adverse events will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03774290
|Unitat de Pneumologia Experimental|
|Barcelona, Spain, 08025|