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

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: Placebo; Drug: PF-06648671

• Registration Number: NCT02407353
• Lead Sponsor: Pfizer

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 Description

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

Study Timeline

• Study First Submitted: 2015-03-25
• Study First Submitted QC: 2015-03-30
• Study First Posted: 2015-04-02
• Study Start: 2015-10
• Status Verified: 2016-03
• Primary Completion: 2016-03
• Study Completion: 2016-03
• Last Update Submitted: 2016-03-21
• Last Update Posted: 2016-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Healthy male and/or female subjects of non childbearing potential
• BMI of 17.5 to 30.5 kg/m2 and a total body weight >50 kg (110 lbs)
• Evidence of a personally signed and dated informed consent document indicating that subject has been informed of all pertinent aspects of the study.

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 the time of dosing)
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study medication (whichever is longer)
• Subjects with a history of significant active bleeding, coagulation disorder or clinically significant finding on prothrombin time/ partial thromboplastin time/International Normalized Ratio (PT/PTT/INR) at Screening
• Subjects with lower spinal malformations (on physical examination), local spinal infection, or other abnormalities that would exclude puncture (LP)
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	Placebo	Subjects receive matching placebo
PF-06648671 Low dose group	PF-06648671	Subjects receive a single oral dose of PF-06648671 lower than 300 mg dose
PF-06648671 Low dose group (2)	PF-06648671	Optional arm. Subjects receive a single oral dose of PF-06648671 at second lower dose if 300 mg dose is not repeated in cohort 2
PF-06648671 High dose group	PF-06648671	subjects receive a single oral dose of PF-06648671 at 300 mg

Primary Outcome Measures

Name	Time	Method
CSF Aβ40 and Aβ42 concentration at maximum change from baseline	0-36 hours postdose

Secondary Outcome Measures

Name	Time	Method
Plasma Decay Half-life (t1/2)	0-72 hours postdose
Maximum Observed Plasma Concentration (Cmax)	0-72 hours postdose
Area Under the Curve from Time Zero to Last Quantifiable Plasma Concentration (AUClast)	0-72 hours postdose
Apparent Oral Clearance (CL/F)	0-72 hours postdose
Area Under the Curve from Time Zero to Last Quantifiable Concentration in CSF (CSF AUClast)	0-36 hours postdose
Number of participants with lab test values of potential clinical importance	0-2 weeks	Pre-defined criteria were established for each lab test to identify potential clinical importance
Number of participants with AEs and SAEs	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
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0-72 hours postdose
Maximum Observed CSF Concentration (CSF Cmax)	0-36 hours postdose
Area Under the Curve From Time Zero to Extrapolated Infinite Time in CSF (CSF AUCinf)	0-36 hours postdose
supine vital sign	0-2 weeks	Measurement of supine vital signs
Electrocardiogram (ECG)	0-2 weeks	Measurement of standard 12-lead ECG (single)
CSF Aβ37, Aβ38 and Aβtotal Concentration	0-36 hours postdose
Area Under the Curve From Time Zero to Extrapolated Infinite Time in Plasma (AUCinf)	0-72 hours postdose
Apparent Volume of Distribution (Vz/F))	0-72 hours postdose
CSF Decay Half-life (CSF t1/2)	0-36 hours postdose
Plasma Aβ40, Aβ42 and Aβtotal	0-72 hours postdose	Plasma Aβ40, Aβ42 and Aβtotal if possible

Trial Locations

Locations (2)

Glendale Adventist Medical Center; 🇺🇸 Glendale, California, United States

California Clinical Trials Medical Group, Inc.; 🇺🇸 Glendale, California, United States