patients with mild-to-moderate persistent atopic asthma MedDRA version: 20.0 Level: LLT Classification code 10003638 Term: Atopic asthma System Organ Class: 100000004855
Conditions
Interventions
Product Name: PBF-680
Product Code: PBF-680
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PBF680
Current Sponsor code: PBF680
Other descriptive name: PBF680
Concentration unit: mg milligram(
Sponsors
Palobiofarma S.L
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. 2. Male and female subjects of 18–65 years age. 3. 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 ICS limited to low/medium dose, or step 4 restricted to medium-dose ICS plus LABA and/or a leukotriene antagonist, as maintenance therapy. Asthma maintenance therapy must have been stable for at least three months before inclusion in the study. Subjects treated with intranasal medication for allergic rhinitis or chronic rhinosinusitis with or without nasal polyposis are allowed to enter the study. The use of oral antihistamines as rescue medication for allergic rhinitis is permitted, subjected to protocol-established washout periods. 4. 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. A historical skin prick test within 12 months before screening is acceptable (supported with source documentation). 5. 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. Acceptable contraception procedures are oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, or use of a condom with spermicide by the sexual partner. Female subjects reporting surgical sterilization must have had the procedure done at least 6 months before the initial dosing of study medication. Surgical sterilization procedures must be supported with clinical documentation made available to the study sponsor. 6. All female subjects must have negative pregnancy test results at screening and baseline. 7. 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. 8. Subjects must weigh at least 45 kg and must have a body mass index (BMI) = 17 kg/m2. 9. Subjects must demonstrate an increase of =12% AND =200 mL in FEV1 over their prebronchodilator value within 30 min after inhaling a total of 400 µg of salbutamol (reversibility test). Reversibility must be demonstrated after an appropriate washout of asthma medications as per ATS/ERS standards for pulmonary function testing. Reversibility can be determined at screening or during the weaning period up to visit V5. 10. Subjects must have a pre-bronchodilator FEV1 =60% and =85% of their predicted normal value, upon completion of LABA and ICS weaning on Visit 5. 11. Subjects must have an ACQ-7 score =1.5 upon completion of LABA and ICS weaning on Visit 5. 12. 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
Exclusion criteria
Exclusion criteria: 1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer. 2. History of hypersensitivity to the study medication or drugs of similar chemical classes (A1 adenosine receptor antagonists). 3. A history of clinically significant ECG abnormalities or a recent history of autonomic dysfunction (e.g. recurrent episodes of fainting, arrhythmia, etc.). 4. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years. 5. Pregnant or nursing (lactating) women. 6. 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. 7. Subjects with severe persistent asthma managed in GINA therapeutic step 4 (except for the restricted allowance in inclusion criterion 3) or 5 according to GINA 2017 guidelines. This criterion includes subjects treated with high-dose ICS, systemic corticosteroids, tiotropium bromide, theophylline or monoclonal antibody-based biological therapies such as omalizumab, mepolizumab, reslizumab, etc. Subjects treated with any immunosuppressant drug, or with systemic corticosteroids for any condition other than asthma, are excluded. Subjects requiring daily use of antihistamine drugs are also excluded. 8. 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. 9. Use of systemic corticosteroids to treat an asthma exacerbation or any other condition within 4 weeks prior to Visit 1. 10. 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. 11. Any disease or illness other than asthma that may require the use of systemic corticosteroids during the study period. 12. Any occupational exposure to allergens/irritants that may have a potential to worsen the asthma symptoms during the trial. 13. 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. 14. 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”. 15. 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 bronchi??s, a-1-antitrypsin deficiency, systemic immune-driven disorders). 16. The use of prescription or over-the-counter medications is subjected to protocol established restrictions (non-permitted medications). 17. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. The investigator must determine this in consideration of the subject's
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate an improvement in trough FEV1 upon a 15-day treatment with PBF-680 compared to placebo in mild-to-moderate asthmatics patients.;Secondary Objective: 1. Determinations of FEV1 area under the curve (AUC). 2. Evaluations on pre- and post-bronchodilator FEV1. 3. Patient reported outcomes (PROs) including Asthma Control Questionnaire-7 (ACQ-7) and Standardized Asthma Quality of Life Questionnaire (AQLQ(s).;Primary end point(s): 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 GINA therapeutic steps 2-3 (except for the use of high-dose inhaled corticosteroid -ICS-) or step 4 restricted to medium-dose ICS plus long-acting ß2-agonist (LABA) bronchodilator and/or a leukotriene receptor antagonist (LTRA) as maintenance therapy.;Timepoint(s) of evaluation of this end point: Day 16 (+2 day leeway) after inclusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To demonstrate an improvement in the AUC30min-23h 30min post-dose through days 15-to-16 (+2 day leeway) upon treatment with PBF-680 compared to placebo. 2. To demonstrate an improvement in the standardized FEV1 AUC30min-6h postdose on day 15 (+2 day leeway) upon treatment with PBF-680 compared to placebo. 3. To demonstrate that PBF-680, compared to placebo, increases prebronchodilator FEV1 at pre-dose spirometry on day 8 (±1 day leeway). 4. To demonstrate that PBF-680, compared to placebo, increases postbronchodilator FEV1 at pre-dose spirometry on day 8 (±1 day leeway) and after the determination of trough FEV1 on day 16 (+2 days leeway). 5. To demonstrate that PBF-680, compared to placebo, provides significantly superior control of asthma as measured by the ACQ-759 and AQLQ(S)60 on days 8 (±1 day leeway) and 15 (+ 2 days leeway). 6. To demonstrate the PBF-680, compared to placebo, provides an improved trend on daily, morning and evening FEV1 and PEF as measured by the subject using an electronic diary/PEF meter device. 7. To demonstrate that PBF-680, compared to placebo, reduces the use of rescue bronchodilator as reported by the subject using an electronic diary/PEF meter device. 8. To assess the safety and tolerability of PBF-680 in the studied mild-to moderate asthmatic population as compared to placebo.;Timepoint(s) of evaluation of this end point: 1. Days 15-to-16 (+2 day leeway). 2. On day 15 (+2 day leeway) 3. On day 8 (±1 day leeway). 4. On day 8 (±1 day leeway) and On day 16 (+2 days leeway). 5. On days 8 (±1 day leeway) and 15 (+ 2 days leeway). 6. From day 1 to day 14 (+2 days leeway) for evening data, and day 2 to day 14 (+2 days leeway) for morning data. The pre-randomization baseline values are the closest available data prior to visit V5. 7. From day 1 to day 14 (+2 days leeway) for evening data, and day 2 to day 14 (+2 days leeway) for morning data. 8. From visit V5 to visit V7. | — |
Countries
Spain
Contacts
Public ContactNahomi Castro Palomino
Palobiofarma S.L
Outcome results
None listed