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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT02407353

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

2.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: PF-06648671 Drug: Placebo	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

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 Concentrations In Cerebrospinal Fluid Using Serial Sampling Methodology

Study Start Date :

Oct 1, 2015

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-06648671 High dose group subjects receive a single oral dose of PF-06648671 at 300 mg	Drug: PF-06648671 Experimental Pfizer compound which will be dosed as oral suspension, single dose at 300 mg and/or 1-2 lower doses
Experimental: PF-06648671 Low dose group Subjects receive a single oral dose of PF-06648671 lower than 300 mg dose	Drug: PF-06648671 Experimental Pfizer compound which will be dosed as oral suspension, single dose at 300 mg and/or 1-2 lower doses
Placebo Comparator: Placebo group Subjects receive matching placebo	Drug: Placebo Placebo which will be dosed as oral suspension, single doses to match PF-06648671
Experimental: PF-06648671 Low dose group (2) 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	Drug: PF-06648671 Experimental Pfizer compound which will be dosed as oral suspension, single dose at 300 mg and/or 1-2 lower doses

Outcome Measures

Primary Outcome Measures

CSF Aβ40 and Aβ42 concentration at maximum change from baseline [0-36 hours postdose]

Secondary Outcome Measures

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
supine vital sign [0-2 weeks]
Measurement of supine vital signs
Electrocardiogram (ECG) [0-2 weeks]
Measurement of standard 12-lead ECG (single)
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]
Area Under the Curve From Time Zero to Extrapolated Infinite Time in Plasma (AUCinf) [0-72 hours postdose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) [0-72 hours postdose]
Plasma Decay Half-life (t1/2) [0-72 hours postdose]
Apparent Oral Clearance (CL/F) [0-72 hours postdose]
Apparent Volume of Distribution (Vz/F)) [0-72 hours postdose]
Maximum Observed CSF Concentration (CSF Cmax) [0-36 hours postdose]
Area Under the Curve from Time Zero to Last Quantifiable Concentration in CSF (CSF AUClast) [0-36 hours postdose]
Area Under the Curve From Time Zero to Extrapolated Infinite Time in CSF (CSF AUCinf) [0-36 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
CSF Aβ37, Aβ38 and Aβtotal Concentration [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Clinical Trials Medical Group, Inc.	Glendale	California	United States	91206
2	Glendale Adventist Medical Center	Glendale	California	United States	91206