A Phase 1, Randomized Investigator-And-Subject-Blind, Sponsor Open, Placebo Controlled Two-Part Study To Characterize The Pharmacokinetics And Pharmacodynamics Of Single Doses Of Pf-05297909 In Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- PF-05297909 25 mg
- Conditions
- Healthy
- Sponsor
- Pfizer
- Enrollment
- 51
- Locations
- 1
- Primary Endpoint
- Plasma area under the curve last (AUClast) pharmacokinetic parameter
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
This study is designed to observe the safety and concentrations of PF-05297909 and proteins in both blood and cerebrospinal fluid after a single dose of PF-05297909 in healthy adults.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For Healthy adult volunteers: healthy male and/or female subjects of non child bearing potential between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and heart rate measurement, 12 lead ECG and clinical laboratory tests.)
Exclusion Criteria
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
Arms & Interventions
Dose Escalation
Ascending doses in healthy volunteers
Intervention: PF-05297909 25 mg
Dose Escalation
Ascending doses in healthy volunteers
Intervention: PF-05297909 100 mg
Dose Escalation
Ascending doses in healthy volunteers
Intervention: PF-05297909 250 mg
Dose Escalation
Ascending doses in healthy volunteers
Intervention: PF-05297909 525 mg
Part 2: CSF PKPD
Pharmacokinetic and pharmacodynamic cerebrospinal fluid assessment
Intervention: PF-05297909 525 mg
Outcomes
Primary Outcomes
Plasma area under the curve last (AUClast) pharmacokinetic parameter
Time Frame: Day 1 to Day 3
Plasma apparent clearance (CL/F) pharmacokinetic parameter
Time Frame: Day 0 to Day 3
Clinical potency of PF 05297909 for reduction in CSF levels of Abeta40, Abeta42, and/or AbetaX via estimation of the IC50 from a population PK/PD (PPK/PD) model
Time Frame: Day 0 to Day 3
Plasma area under the curve infinity (AUCinf) pharmacokinetic parameter
Time Frame: Day 1 to Day 3
Plasma half-life (t1/2) pharmacokinetic parameter
Time Frame: Day 1 to Day 3
Plasma apparent volume of distribution (Vz/F) pharmacokinetic parameter
Time Frame: Day 1 to Day 3
CSF concentration summary by time point for PF 05297909.
Time Frame: Day 1 to Day 3
Change from baseline in CSF levels of Abeta40
Time Frame: Day 1 to Day 3
Change from baseline in CSF levels of Abeta42
Time Frame: Day 1 to Day 3
Change from baseline in CSF levels of AbetaX
Time Frame: Day 1 to Day 3
Change from baseline in CSF levels of sAPPalpha
Time Frame: Day 1 to Day 3
Change from baseline in CSF levels of sAPPbeta.
Time Frame: Day 1 to Day 3