Clinical Trial: Safety, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Repeat Doses of Inhaled GSK2269557 in Patients With APDS/PASLI

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An Open-label, Single Arm Study to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of Repeat Doses of Inhaled GSK2269557 in Patients With APDS/PASLI

Brief Summary: This is a multi-center, non-randomised, open-label, uncontrolled, single group study to investigate the safety and pharmacokinetics (PK) during 84 days repeat dosing treatment with 1000 micrograms (mcg) of inhaled GSK2269557 in addition to standard of care, in subjects with activated phosphoinositide 3-kinase (PI3K) delta syndrome /p110delta-activating mutation causing senescent T Cells, lymphadenopathy and immunodeficiency (APDS/PASLI). To date GSK2269557 has been administered to healthy subjects (smokers and non smokers), subjects with: stable Chronic Obstructive Pulmonary Disease (COPD); subjects experiencing a COPD exacerbation; and subjects with persistent, uncontrolled asthma. As this study is the first administration of GSK2269557 to subjects with APDS, this study will provide safety, tolerability, efficacy and pharmacokinetic data in this patient population. Up to 20 subjects will be enrolled into the study. The total duration of the study is approximately 30 weeks, including pre-screening/screening and follow-up.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Number of subjects with any adverse events (AE) [ Time Frame: Up to 6 months ]
    An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
  • Systolic and diastolic blood pressure as a measure of safety [ Time Frame: Up to 7.5 months ]
    Systolic and diastolic blood pressure will be measured in semi-supine position after 5 minutes rest.
  • Temperature as a measure of safety [ Time Frame: Up to 7.5 months ]
    Temperature will be measured in semi-supine position after 5 minutes rest.
  • Pulse rate as a measure of safety [ Time Frame: Up to 7.5 months ]
    Pulse rate will be measured in semi-supine position after 5 minutes rest.
  • Respiratory rate as a measure of safety [ Time Frame: Up to 7.5 months ]
    Respiratory rate will be measured in semi-supine position after 5 minutes rest.
  • 12-lead electrocardiogram (ECG) as a measure of safety [ Time Frame: Up to 7.5 months ]
    Single (triplicate at screening) 12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
  • Composite of hematology parameters as a measure of safety [ Time Frame:&nbs

    Original Primary Outcome: Same as current

    Current Secondary Outcome: GSK2269557 trough plasma concentration following single and repeated treatment [ Time Frame: Pre-dose, 5 minutes, 3 hours and 24 hours post-dose on Day 1 and pre-dose on Days 2, 14, and 83 and early withdrawal ]

    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: October 29, 2015
    Date Started: July 22, 2016
    Date Completion: December 7, 2018
    Last Updated: April 27, 2017
    Last Verified: April 2017