Clinical Trial: A Study to Evaluate the Pharmacodynamic Effects of Single Oral Doses of PF-06648671 on β-Amyloid (Aβ) Concentrations in Cerebrospinal Fluid (CSF)

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

Official Title: A Phase 1 Investigator-and-subject Blind, Randomized, Placebo Controlled, Parallel Study In Healthy Subjects To Evaluate The Pharmacodynamic Effects Of Single Oral Doses Of Pf-06648671 On Aβ Conc

Brief Summary: This is phase 1 investigator-and-subject blind, sponsor open, randomized, placebo controlled, parallel study in healthy subjects to evaluate the pharmacodynamics effect of single oral doses of PF-06648671 on CSF Aβ concentrations using serial CSF sampling methodology.

Detailed Summary: This study is investigator-and-subject blind, sponsor open, randomized, placebo-controlled, parallel study in healthy subjects to evaluate central (CSF) and peripheral (plasma) pharmacodynamics effects (Abeta) over 36 hours post single doses of PF-06648671. Two cohorts will be run in sequential. the first cohort is to evaluate the Abeta effect at top dose of 300 mg PF-06648671 and second cohort is to evaluate the Abeta effect at top dose (if more subjects are required) and/or 1-2 lower doses
Sponsor: Pfizer

Current Primary Outcome: CSF Aβ40 and Aβ42 concentration at maximum change from baseline [ Time Frame: 0-36 hours postdose ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of participants with AEs and SAEs [ Time Frame: 0-2 weeks ]
    Counts of participants who have TEAEs, defined as newly occuring or worsening after first dose. Relatedness to PF-06648671 will be assessed by the investigator (Yes/No). Participants with multiple occurrence of an AE within a category will be counted once within the category
  • supine vital sign [ Time Frame: 0-2 weeks ]
    Measurement of supine vital signs
  • Electrocardiogram (ECG) [ Time Frame: 0-2 weeks ]
    Measurement of standard 12-lead ECG (single)
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0-72 hours postdose ]
  • Area Under the Curve from Time Zero to Last Quantifiable Plasma Concentration (AUClast) [ Time Frame: 0-72 hours postdose ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time in Plasma (AUCinf) [ Time Frame: 0-72 hours postdose ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0-72 hours postdose ]
  • Plasma Decay Half-life (t1/2) [ Time Frame: 0-72 hours postdose ]
  • Apparent Oral Clearance (CL/F) [ Time Frame: 0-72 hours postdose ]
  • Apparent Volume of Distribution (Vz/F)) [ Time Frame: 0-72 hours postdose ]
  • Maximum Observed CSF Concentration (CSF Cmax) [ Time Frame: 0-36 hours postdose ]
  • Area Under the Curve from Time Zero to Last Quantifiable Concentration in CSF (CSF AUClast) [ Time Frame: 0-36 hours postdose ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time in CSF (CSF AUCinf) [ Time Frame: 0-36 hours postdose ]
  • CSF Decay Half-life (CSF t1/2) [ Time Frame: 0-36 hours postdose ]
  • Plasma Aβ40, Aβ42 and Aβtotal [ Time Frame: 0-72 hours postdose ]
    Plasma Aβ40, Aβ42 and Aβtotal if possible
  • CSF Aβ37, Aβ38 and Aβtotal Concentration [ Time Frame: 0-36 hours postdose ]
  • Number of participants with lab test values of potential clinical importance [ Time Frame: 0-2 weeks ]
    Pre-defined criteria were established for each lab test to identify potential clinical importance


Original Secondary Outcome:

  • Number of participants with AEs and SAEs [ Time Frame: 0-2 weeks ]
    Counts of participants who have TEAEs, defined as newly occuring or worsening after first dose. Relatedness to PF-06648671 will be assessed by the investigator (Yes/No). Participants with multiple occurrence of an AE within a category will be counted once within the category
  • supine vital sign [ Time Frame: 0-2 weeks ]
    Measurement of supine vital signs
  • Electrocardiogram (ECG) [ Time Frame: 0-2 weeks ]
    Measurement of standard 12-lead ECG (single)
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0-72 hours postdose ]
  • Area Under the Curve from Time Zero to Last Quantifiable Plasma Concentration (AUClast) [ Time Frame: 0-72 hours postdose ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time in Plasma (AUCinf) [ Time Frame: 0-72 hours postdose ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0-72 hours postdose ]
  • Plasma Decay Half-life (t1/2) [ Time Frame: 0-72 hours postdose ]
  • Apparent Oral Clearance (CL/F) [ Time Frame: 0-72 hours postdose ]
  • Apparent Volume of Distribution (Vz/F)) [ Time Frame: 0-72 hours postdose ]
  • Maximum Observed CSF Concentration (CSF Cmax) [ Time Frame: 0-36 hours postdose ]
  • Area Under the Curve from Time Zero to Last Quantifiable Concentration in CSF (CSF AUClast) [ Time Frame: 0-36 hours postdose ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time in CSF (CSF AUCinf) [ Time Frame: 0-36 hours postdose ]
  • CSF Decay Half-life (CSF t1/2) [ Time Frame: 0-36 hours postdose ]
  • Plasma Aβ40, Aβ42 and Aβtotal [ Time Frame: 0-72 hours postdose ]
  • CSF Aβ37, Aβ38 and Aβtotal Concentration [ Time Frame: 0-36 hours postdose ]
  • Number of participants with lab test values of potential clinical importance [ Time Frame: 0-2 weeks ]
    Pre-defined criteria were established for each lab test to identify potential clinical importance


Information By: Pfizer

Dates:
Date Received: March 25, 2015
Date Started: October 2015
Date Completion:
Last Updated: March 21, 2016
Last Verified: March 2016