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Study to Assess the Efficacy of a Single PBF-680 Oral Administration to Attenuate Adenosine 5'-Monophosphate Challenge-induced Airway Hyperresponsiveness in Mild-to-moderate Asthmatics

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01939587
Recruitment Status : Completed
First Posted : September 11, 2013
Last Update Posted : March 8, 2016
Palo Biofarma, S.L
Information provided by (Responsible Party):
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Brief Summary:

This is a single-center, double-blind, randomized trial utilizing a three-period, balanced block design, with each period comprising a unique study product administration. The treatments studied are PBF-680 5 mg, PBF-680 20 mg and placebo, as an orally administered capsule. The study includes a screening visit, a selection visit, three visits for the randomized treatment sequence, and an end-of-study follow-up visit, spanning through a 65-day maximum study duration. The study will be conducted on 18 male or female adults aged ³18 years, with a diagnosis of stable, mild to moderate asthma as per GINA guidelines, with no smoking or less than a 5 packs-years smoking history history, responsive to AMP airway challenge as determined in the selection visit.

The primary efficacy variable will be the PC20 yielded from AMP airway challenge testing at the three treatment visits. FeNO, sampled at three time points at each treatment period visit, will be a exploratory variable. Safety assessment will include monitoring of adverse events, physical examination, vital signs, EKGs, spirometry, serum and urine pregnancy tests, and laboratory determinations. Blood sampling at a time-point series will provide pharmacokinetics data.

The primary variable of the study is PC20, mg×mL-1. The PC 20 distributions will be analyzed by treatment using ANOVA for repeated measurements, followed by post hoc pairwise comparisons as appropriate. Other analyses will comprise FeNO, pharmacokinetics, data sets generated from baseline characteristics and safety assessments, and discretionary expiratory analyses to evaluate the influence of baseline and clinical covariates on the primary variable.

Condition or disease Intervention/treatment Phase
Asthma Drug: PBF-680 5 mg Drug: PBF-680 20 mg Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Single-centre, Randomised, Double-blind, Placebo-controlled, 3-way Multiple Dose, Cross-over, "Proof-of-concept" Study to Assess the Efficacy of a Single PBF-680 Oral Administration to Attenuate Adenosine 5'-Monophosphate (AMP) Challenge-induced Airway Hyperresponsiveness in Mild-to-moderate Asthmatics
Study Start Date : December 2013
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Adenosine

Arm Intervention/treatment
Experimental: PBF-680 5 mg
5 mg of PBF-680
Drug: PBF-680 5 mg
Experimental: PBF-680 20 mg
20 mg of PBF-680
Drug: PBF-680 20 mg
Placebo Comparator: Placebo
Drug: Placebo

Primary Outcome Measures :
  1. Change in PC20 yielded from AMP airway challenge testing [ Time Frame: 2.25, 3.5, 8 hours post dose ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male and female adults aged 18, who have signed the informed consent form prior to initiation of any study procedures.
  • Subjects with mild to moderate asthma, diagnosed as per Global Initiative for Asthma(GINA) guidelines.
  • Subjects must have a body mass index between 18 and 35 kg/m².
  • Subjects must be able to perform acceptable spirometry in accordance with ATS/ERS criteria for acceptability repeatability.
  • Subjects must have a baseline FEV1 60% of predicted normal, and greater than 1 L in absolute value, on Visit 2.
  • On Visit 2, eligible subjects must show airway hyperresponsiveness to AMP, determined by PC20 thresholding (the AMP provocative concentration that elicits a 20% drop from baseline FEV1 value, under AMP challenge test as per the ERS Task Force on Indirect Airway Challenges).

Exclusion Criteria:

  • Current smokers, smokers within six months prior to Visit 1, or subjects with an smoking history greater than 5 pack-years.
  • Asthmatics in treatment Step 5 as per GINA guidelines, including oral corticosteroids and/or omalizumab, or any immunosuppressive medication whether asthma-related or indicated for any concomitant morbidities.
  • Subjects with a history of life-threatening asthma attacks (i.e. requiring ICU admission, orotracheal intubation).
  • Subjects with a history of a respiratory tract infection or an asthma crisis requiring the use of antibiotics and/or systemic corticosteroids within 4 weeks prior to Visit 1, or who develop a respiratory tract infection or asthma crisis during the screening period. In the latter case, the subjects can be re-screened four weeks after the last dose of systemic corticosteroid or antibiotic.
  • Subjects that received bronchial thermoplastic treatment.
  • Subjects with concomitant pulmonary or thoracic disease other than asthma that could interfere safety or efficacy as per site investigator assessment. This includes, but is not limited to, COPD attributable to tobacco or alpha-1 antitrypsin deficiency, cystic fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, active pulmonary tuberculosis, or any prior condition that led to pulmonary resection surgery or lung transplantation. Non-cystic fibrosis bronchiectasis without clinically significant morbidity, moderate alpha-1 antitrypsin deficiency without evidence of emphysema or related COPD, or past pulmonary tuberculosis that received proper medical treatment, are acceptable provided that the condition is not expected to interfere with pulmonary function testing as per site investigator assessment.
  • Subjects with symptoms of angina pectoris or with a history of confirmed coronary disease or cardiomyopathy.
  • Subjects with A-V block in any degree, sinus bradycardia, tachyarrhythmia, unstable atrial fibrillation, long QT syndrome, QTc(F) interval greater than 450 ms at screening(Visit 2), or any other EKG abnormality deemed clinically significant by the investigator.
  • Subjects who have a clinically significant laboratory abnormality at screening (Visit 2).
  • Subjects with current uncontrolled arterial hypertension.
  • Women of child-bearing potential, unless they are surgically sterile (i.e. bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy), are at least 2 years postmenopausal, practice abstinence, or agree to employ effective contraception from Visit 1 through Visit 6. 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.
  • Women supplying lactation.
  • Receipt of any investigational drug therapy or biologicals within 3 months before randomization in this study, or within 5 half-lives of the investigational agent or biologic, whichever is longer.
  • History of any known immunodeficiency disorder.
  • Subjects with a history of malignancy within the past five years, with the exception of localized basal cell carcinoma of the skin.
  • History of treatment for alcohol or drug abuse within the past year.
  • Subjects with any comorbidity that could affect the safety or efficacy as per site investigator assessment.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01939587

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Palobiofarma S.L. (molecule owner)
Mataró, Barcelona, Spain, 08302
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Sponsors and Collaborators
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Palo Biofarma, S.L

Additional Information:
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Responsible Party: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau Identifier: NCT01939587     History of Changes
Other Study ID Numbers: IIBSP-PBF-2013-93
2013-002906-30 ( EudraCT Number )
First Posted: September 11, 2013    Key Record Dates
Last Update Posted: March 8, 2016
Last Verified: March 2016

Keywords provided by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau:
Adenosine A1 receptor antagonist
adenosine receptor modulator

Additional relevant MeSH terms:
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Respiratory Hypersensitivity
Respiratory Tract Diseases
Hypersensitivity, Immediate
Immune System Diseases
Adenosine A1 Receptor Antagonists
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists