SAD/MAD Study of a New Formulation of Nebulised RPL554 in Healthy Subjects and COPD Subjects
Condition: Inflammatory Disorder of the Respiratory Tract; Chronic Obstructive Pulmonary Disorder
MeSH terms: Lung Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to assess the safety of single doses and multiple doses of a new
      formulation of RPL554 in healthy subjects and subjects with chronic obstructive pulmonary
      disorder.
    

Detailed description: 
      This is a randomised, double blind, placebo controlled study of a new suspension formulation
      of RPL554 comprising a Single Ascending Dose (SAD) phase (Part A) in healthy subjects, a
      Multiple Ascending Dose (MAD) phase (Part B) in healthy subjects and a MAD phase (Part C) in
      stable chronic obstructive pulmonary disease (COPD) subjects. Each cohort should comprise 10
      subjects in a 7 active: 3 placebo ratio

      Subjects will be screened in the 14 days before the first dose of study drug and have an end
      of study visit 4 to 10 days after the last dose of study drug.

      Part A. Single Ascending Dose Study in Healthy Male Subjects aged 18-50. Each subject will
      receive a single dose of study drug. The starting dose will be 1.5 mg with planned escalation
      as 2 fold multiples unless the safety data indicates the escalation should be at smaller
      intervals. If RPL554 is not well tolerated at a particular dose level, the dose may be
      reduced for the next cohort.The decision on whether or not to escalate to each new dose
      level, and the dose, will be based on a formal review by the Dose Review Group (DRG).

      Part B. Multiple Ascending Dose Study in Healthy Male Subjects aged 18-50. The starting dose
      for Part B will be determined from the data in Part A of the study. Each subject will receive
      the following doses of study drug and will be confined to the study centre during dosing:
      three doses at intervals of 8 hours on Days 1 to 5, followed by a single morning dose on Day
      6.

      The DRG may determine on the basis of safety or PK data that the dosing interval for
      subsequent cohorts will be every 12 hours, rather than every 8 hours.

      Part C. Multiple Ascending Dose in moderate, stable COPD Subjects aged 40-75 Subjects will
      have no known significant concurrent diseases, will not have had a recent exacerbation, and
      will be expected to be able to withhold regular bronchodilator therapy for the duration of
      the treatment phase of the study. Rescue medication with ipratropium will be allowed (and its
      use recorded) and subjects may continue inhaled corticosteroids at a stable dose.

      The dosing schedule will be the same as for Part B

      Dose Escalation Procedures The decision on whether or not to escalate to each new dose level
      and from one part of the study to the next and the selected dose will be based on a formal
      review by the DRG of safety data.

      The DRG will include the Principal Investigator and Sponsor's Medical Expert (and/or
      delegates) and will meet by teleconference to review safety data for each cohort. The DRG
      will review all available safety data (including adverse events [AEs], safety laboratory
      tests, spirometry and ECG data) collected up to 24 hours post dose for Part A, and for up to
      24 hours post final dose for Parts B and C.

      Data collected during the study will be entered on case report forms and transferred to a
      database using double entry. Blinding will be maintained until all queries are resolved and
      the database is locked. AEs will be summarised by study treatment and further by intensity
      and relationship to study treatment. The study will primarily be evaluated using descriptive
      statistics.

      The sample size selected is not based on any formal power calculation.
    

Intervention name(s): RPL554; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Phosphodiesterase 3 and 4 Inhibitor; Dummy solution
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: COPD