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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02407353
• Other study ID #: B7991003
• Status: Completed
• Phase: Phase 1
• First received: March 25, 2015
• Last updated: March 21, 2016
• Start date: October 2015
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

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
Placebo which will be dosed as oral suspension, single doses to match PF-06648671

Locations

Country	Name	City	State
United States	California Clinical Trials Medical Group, Inc.	Glendale	California
United States	Glendale Adventist Medical Center	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CSF Aß40 and Aß42 concentration at maximum change from baseline		0-36 hours postdose	No
Secondary	Number of participants with AEs and SAEs	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	0-2 weeks	Yes
Secondary	supine vital sign	Measurement of supine vital signs	0-2 weeks	Yes
Secondary	Electrocardiogram (ECG)	Measurement of standard 12-lead ECG (single)	0-2 weeks	Yes
Secondary	Maximum Observed Plasma Concentration (Cmax)		0-72 hours postdose	No
Secondary	Area Under the Curve from Time Zero to Last Quantifiable Plasma Concentration (AUClast)		0-72 hours postdose	No
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time in Plasma (AUCinf)		0-72 hours postdose	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		0-72 hours postdose	No
Secondary	Plasma Decay Half-life (t1/2)		0-72 hours postdose	No
Secondary	Apparent Oral Clearance (CL/F)		0-72 hours postdose	No
Secondary	Apparent Volume of Distribution (Vz/F))		0-72 hours postdose	No
Secondary	Maximum Observed CSF Concentration (CSF Cmax)		0-36 hours postdose	No
Secondary	Area Under the Curve from Time Zero to Last Quantifiable Concentration in CSF (CSF AUClast)		0-36 hours postdose	No
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time in CSF (CSF AUCinf)		0-36 hours postdose	No
Secondary	CSF Decay Half-life (CSF t1/2)		0-36 hours postdose	No
Secondary	Plasma Aß40, Aß42 and Aßtotal	Plasma Aß40, Aß42 and Aßtotal if possible	0-72 hours postdose	No
Secondary	CSF Aß37, Aß38 and Aßtotal Concentration		0-36 hours postdose	No
Secondary	Number of participants with lab test values of potential clinical importance	Pre-defined criteria were established for each lab test to identify potential clinical importance	0-2 weeks	Yes

External Links

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