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

NCT03774290 | Completed Phase 2

• 1 other identifier: PBF-680CT-05
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Effect of PBF-680 on trough forced expiratory volume in 1 second (FEV1)

  Defined as the average of the FEV1 measurements taken at 23h 15min and 23h 45min post-dose after the final dose.

  16 Days

Secondary Outcomes (8)

• Effect of PBF-680 in the FEV1 area under curve AUC30min-23h 30min post-dose

  16 days

• Effect of PBF-680 in the standardized FEV1 AUC30min-6h post- dose

  15 Days

• Effect of PBF-680 in the pre-bronchodilator FEV1

  8 days

• Effect of PBF-680 in the post- bronchodilator FEV1 at pre-dose spirometry on day 8

  Day 8 and Day 16

• Effect of PBF-680 on the asthma control as measured by Asthma Questionnaires

  Day 8 and Day 15

Study Arms (2)

PBF-680 10 mg

EXPERIMENTAL

10 mg of PBF-680 once a day

Drug: PBF-680

Placebo oral capsules

PLACEBO COMPARATOR

Placebo once a day

Drug: Placebo oral capsule

Interventions

PBF-680 DRUG

PBF-680 is an adenosine A1 receptor antagonist

PBF-680 10 mg

Placebo oral capsule DRUG

Oral gelatine capsule

Placebo oral capsules

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained before any study assessments are performed. Subjects must be able to communicate well with the investigator and staff so that they can understand and comply with the requirements of the study.
• Male and female subjects of 18-65 years age.
• Subjects with a medical history of mild-to-moderate persistent allergic asthma, diagnosed according to GINA 2017 guidelines, and managed in therapeutic steps 2-3 being inhaled corticosteroid (ICS) limited to low/medium dose, or step 4 restricted to medium-dose ICS plus ong-acting beta2-agonist (LABA) and/or a leukotriene antagonist, as maintenance therapy.
• A positive skin prick test to aeroallergens, such as house dust mite, tree or grass pollen, pet dander, or cockroach antigens. In addition, any allergens specific to the country/locality can be included.
• Women of child-bearing potential must agree to employ effective contraception from Visit 1 through FU visit, unless they are surgically sterile (i.e. bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy), are at least 2 years postmenopausal, or practice abstinence.
• All female subjects must have negative pregnancy test results at screening and baseline.
• Male subjects must agree to use two acceptable methods of contraception, (e.g. spermicidal gel plus condom) for the entire duration of the study and up to the study completion visit, and refrain from fathering a child within the three months following the last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception.
• Subjects must weigh at least 45 kg and must have a body mass index (BMI) ≥ 17 kg/m2.
• Evidence of asthma as documented by either:
• Subjects must demonstrate an increase of ≥12% AND ≥200 mL in FEV1 over their pre- bronchodilator value within 30 min after inhaling a total of 400 μg of salbutamol (reversibility test). Reversibility can be documented prior to Screening (Visit 1) or determined at screening or during the weaning period up to visit V5.
• Or documented history of bronchial hyper reactivity (e.g. fall in FEV1 from baseline of more than or equal to 20 percent with inhaled standard doses of Adenosine monophosphate, methacholine or histamine, or more than or equal to 15 percent with standardized hyperventilation, hypertonic saline or mannitol challenge) from a bronchoprovocation study \[e.g. methacholine challenge prior to Screening (Visit 1)\].
• Or a decrease ≥ 5% of their initial FEV1 measured at V1 during the weaning period up to visit V5.
• Subjects must have either a pre-bronchodilator FEV1 ≥60% and ≤90% of their predicted normal value upon completion of LABA and ICS weaning on Visit 5 or a decrease ≥ 5% of their initial FEV1 measured at V1 during the weaning period up to visit V5.
• Subjects must have an ACQ-7 score ≥1.5 upon completion of LABA and ICS weaning on Visit 5.
• Subjects must meet a ≥80% compliance with the morning and evening electronic/PEF meter recordings during the weaning of their asthma maintenance therapy (i.e. from visit V2 to visit V5).

You may not qualify if:

• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
• History of hypersensitivity to the study medication or drugs of similar chemical classes (A1 adenosine receptor antagonists).
• A history of clinically significant ECG abnormalities or a recent history of autonomic dysfunction (e.g. recurrent episodes of fainting, arrhythmia, etc.).
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
• Pregnant or nursing (lactating) women.
• Smokers, defined by smoking within the previous 6 months or having a smoking history of more than 10 packs-years, a pack-year being defined as smoking the equivalent of 20 cigarettes (a pack) per day for 1 year.
• Present or past use of a biologic (e.g. monoclonal antibodies) agent for the treatment of asthma. Use of a biologic agent for any other condition within the past 6 months.
• Use of systemic corticosteroids to treat an asthma exacerbation or any other condition within 4 weeks prior to Visit 1.
• History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest and/or hypoxic seizures. History of asthma exacerbations that required ward hospitalization or an emergency room stay greater than 48 hours within 5 years prior to Visit 1.
• Any disease or illness other than asthma that may require the use of systemic corticosteroids during the study period.
• Any occupational exposure to allergens/irritants that may have a potential to worsen the asthma symptoms during the trial.
• A respiratory tract infection requiring the use of antibiotics within 4 weeks prior to visit V1, or pneumonia within 6 months prior to visit V1.
• An asthma exacerbation requiring treatment or the use of any health care resources within 4 weeks prior to visit V1. This includes asthma exacerbations managed with a transient increase of the subject's regular asthma maintenance therapy, and self- managed exacerbations using an "action plan".
• Subjects with any other underlying diseases that may compromise safety or may interfere with efficacy outcomes (e.g. tuberculosis, clinically relevant bronchiectasis, diffuse lung interstitial disease, pulmonary hypertension, emphysema, chronic bronchitis, alpha-1-antitrypsin deficiency, systemic immune-driven disorders).
• The use of prescription or over-the-counter medications is subjected to protocol- established restrictions (non-permitted medications)

Sponsors & Collaborators

• Palobiofarma SL: lead
• Pivotal S.L.: collaborator

Study Sites (1)

Unitat de Pneumologia Experimental

Barcelona, 08025, Spain

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: December 12, 2018
• Study Start: June 1, 2018
• Primary Completion: February 5, 2020
• Study Completion: March 16, 2020
• Last Updated: September 25, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)