"First-in-human" Study To Assess the Safety and Tolerability of PBF-680 in Male Healthy Volunteers
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase I, single-center, randomized, double-blind, dose escalation study without
      therapeutic benefit, in which PBF-680 will be administered as single oral ascending dose to
      young male healthy volunteers. Up to four different rising doses will be tested in groups of
      8 participants. Thus, four groups will participate but each one participating only once. For
      each dose level / group the participants will be randomized to active or placebo with 2
      participants being randomly assigned to placebo and 6 to the active drug. First, one
      volunteer will receive active drug (subgroup 1); after 48h of safety and tolerability
      assessment a second subgroup of 3 volunteers will receive 2 active drug and 1 placebo; after
      48h of safety and tolerability parameters assessment a third subgroup of 4 volunteers will
      receive 3 active drug and 1 placebo. After evaluation of safety parameters of dose level the
      process will replicate one week afterwards in the following dosages.

      The aims of this study are:

      Primary:

      - To assess the safety and tolerability of single escalating oral doses of PBF-680 in young
      male healthy subjects leading to the determination of the maximum tolerated dose (MTD).

      Secondary:

        -  To assess the pharmacokinetics of PBF-680 after single rising oral doses in healthy
           young male subjects.

        -  To asses the preliminary pharmacodynamic effects.

        -  To evaluate the adenosine A1 receptor antagonism in blood samples of healthy volunteer
           caused by the PBF-680 administration
    

Detailed description: 
      In order to assess the safety and tolerability of single escalating oral doses of PBF-680,
      safe measurements (ECG, vital signs, blood chemistry and hematology) will be conducted
      before, during and follow-up study course.

        -  Physical Examination. Physical examination data will be collected at screening and at
           the end of the study. All occurring abnormalities will be displayed by subjects. Vital
           Signs. Vital signs (DINAMAP V100) including measurements of blood pressure, pulse and
           respiratory rate and digital axillary temperature will be obtained at screening, during
           study and at study completion (follow up). All occurring abnormalities will be displayed
           by subjects.

        -  Adverse Events. All information obtained on adverse events will be displayed and tallied
           by treatment /dose. Laboratory variables (Hematology, Biochemistry and Urinalysis):
           Clinical laboratory data will be collected at screening, during study and at study
           completion(follow up). All subjects with values outside of the normal range for any
           variable will be identified. All occurring abnormalities will be displayed by subjects.

        -  Electrocardiographic Evaluation. An electrocardiogram will be performed at several
           times, at screening, during the study and at completion of the study (follow up).
           Description of ECG intervals will be also done. All occurring abnormalities will be
           identified.

      Also, as secondary variables will be evaluated:

        -  Pharmacokinetic profile analysis. The variable for the pharmacokinetic evaluation will
           be the parameter that defines the bioavailability in extend and rate Ln [AUC 0t](AUC:
           area under curve), Ln [Cmax] of experimental products and placebo. For this purpose the
           necessary kinetic parameters will be determined by means of a non compartmental method
           with the values obtained after the quantitative analysis of the plasma levels of
           PBF-680. The following pharmacokinetic parameters will be obtained from each individual
           plasma concentration versus time profile using standard methods, if the data warrant
           doing so

        -  Pharmacodynamic effects. To asses the preliminary pharmacodynamic effects of PBF-680 at
           each dose level, subjective tests (VAS) and (LSEQ) before and after different times
           post-drug administration will be conducted. Effects on the CNS (Central Nervous system)
           will be evaluated by analyzing of the changes observed in the different time for
           subjective assessment scales.
    

Intervention name(s): PBF-680; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Dose: 10, 20, 40 ,60 mg/day (making combination of 5 y 20 mg forms).; 1 or 2 or 3 capsules of placebo.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Adenosine A1 receptor antagonist; Asthma; adenosine receptor modulator; COPD