Clinical Trial: Pharmacokinetic (PK) Study of GSK933776 in Healthy Volunteers

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Open Label, Parallel-Group Study to Estimate Bioavailability and to Assess the Pharmacokinetic Profile, Safety and Tolerability of GSK933776 Administered by Subcutaneous or Intramuscular

Brief Summary: This study is intended to enable a possible transition to intramuscular (IM) or subcutaneous (SQ) administration for subsequent studies with GSK933776 by characterizing the safety, tolerability, PK and pharmacodynamic profiles, and immunogenicity of GSK933776 following IM and SQ administration in healthy volunteers. Such alternate routes of administration may provide more options in the selection of an efficacious dose for subsequent development in patients with geographic atrophy. There will be four treatment arms in the study and participants will be assigned to 1 of 4 possible treatment arms in a 1:1:1:1 ratio. The planned number of evaluable participants for this study is 24 with 6 participants completing all critical assessments in each of the four treatment arms. The total duration of participation from screening to follow-up for Treatment Arms A, B and D (single dose of GSK933776), will be approximately 113 days and total duration for Treatment Arm C (repeat dose of GSK933776) will be approximately 134 days.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Relative bioavailability of GSK933776 after single dose SQ or IM administration as compared to IV infusion [ Time Frame: Blood samples will be collected at following time points: pre-dose and at (0.25, 0.5, 0.75, 1, 2, 4 hours only for IV infusion), 6, 24, 48, 72, 96, 120, 216, 336, 504, 672, 1344 and 2016 hours post dose ]
    Bioavailability is defined as the rate and extent to which drug reaches the systemic circulation. The relative bioavailability will be calculated from the ratio of area under concentration time curve from time zero to infinity (AUC [0-infinity]) following single dose SQ and IM injection to intravenous (IV) infusion
  • Relative bioavailability of GSK933776 after repeat dose SQ administration as compared to IV infusion [ Time Frame: Blood samples will be collected at following time points: pre-dose, 6, 24, 48, 72, 96 and 120 hours post dose in each of the 4 dosing weeks and additionally at 216, 336, 504, 672, 1344 and 2016 hours post last dose ]
    Bioavailability is defined as the rate and extent to which drug reaches the systemic circulation. The relative bioavailability will be calculated from the ratio of AUC (0-infinity) following SQ repeat dose injections to intravenous (IV) infusion


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Composite of PK parameters of GSK933776 following single dose IM and SQ administration as compared to IV administration [ Time Frame: Samples will be collected at following time points: pre-dose and at (0.25, 0.5, 0.75, 1, 2, 4 hours only for IV infusion), 6, 24, 48, 72, 96, 120, 216, 336, 504, 672, 1344 and 2016 hours post dose ]
    PK parameters include: area under the concentration-time curve over the dosing interval (AUC[0-tau]), maximum concentration (Cmax), time of occurrence of Cmax (Tmax), terminal phase half-life (T1/2), clearance, and volume of distribution as data permit
  • Composite of PK parameters of GSK933776 following repeat dose SQ administration as compared to IV administration [ Time Frame: Blood samples will be collected at following time points: pre-dose, 6, 24, 48, 72, 96 and 120 hours post dose in each of the 4 dosing weeks and additionally at 216, 336, 504, 672, 1344 and 2016 hours post last dose. ]
    PK parameters include: AUC(0-tau), Cmax, Tmax, T1/2, clearance, and volume of distribution as data permit
  • Number of participants with adverse events as a measure of safety and tolerability following single dose administration [ Time Frame: Up to 113 days ]
    AEs will be collected from the start of Study Treatment and until the follow-up contact
  • Clinical observation following IV, SQ and IM single dose administration as a measure of safety and tolerability [ Time Frame: Up to 134 days ]
    AEs will be collected from the start of Study Treatment and until the follow-up contact
  • Clinical observation following IV, SQ and IM repeat dose administration as a measure of safety and tolerability [ Time Frame: Up to 113 days ]
    Clinical observation include: physical examination, medical history, and review of concomitant medication
  • Vital sign measurement following single dose administration as a measure of safety and tolerability [ Time Frame: Up to 134 days ]
    Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and body temperature measurement.
  • Vital sign measurement following repeat dose administration as a measure of safety and tolerability [ Time Frame: Up to 134 days ]
    Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and body temperature measurement.
  • Electrocardiogram (ECG) measurement following single dose administration to assess safety and tolerability [ Time Frame: Up to 113 days ]
    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 QT interval corrected for heart rate (QTc interval).
  • ECG measurement following repeat dose administration to assess safety and tolerability [ Time Frame: Up to 134 days ]
    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 interval.
  • Clinical laboratory parameters assessment following single dose administration as a measure of safety and tolerability [ Time Frame: Up to 113 days ]
    Clinical laboratory assessment include: hematology, clinical chemistry, urinalysis and additional parameters.
  • Clinical laboratory parameters assessment following repeat dose administration as a measure of safety and tolerability [ Time Frame: Up to 134 days ]
    Clinical laboratory assessment include: hematology, clinical chemistry, urinalysis and additional parameters.
  • Plasma concentrations of GSK933776, total amyloid beta (AB), total AB fragments, as well as unbound concentrations of AB, fragments containing the epitope 1-22, as data permit following single dose administrationof GSK933776 [ Time Frame: Up to 113 days ]
    The relationship between plasma concentration of GSK933776 and plasma concentration of total and free amyloid beta will be explored as data permit
  • Plasma concentration of GSK933776, AB, total AB fragments, as well as unbound concentrations of AB, fragments containing the epitope 1-22, as data permit following repeat dose administration [ Time Frame: Up to 134 days ]
    The relationship between plasma concentration of GSK933776 and plasma concentration of total and free amyloid beta will be explored as data permit
  • Presence of antibodies to GSK933776 in serum samples following single dose administration of GSK933776 [ Time Frame: Up to 113 days ]
    To characterize the immunogenicity profile of GSK933776 following IV, IM and SQ administration. Samples will be analyzed for the presence of anti-GSK933776 antibodies by immun

    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: January 9, 2014
    Date Started: January 22, 2014
    Date Completion:
    Last Updated: May 12, 2017
    Last Verified: May 2017