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

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: PF-06648671; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02407353

B7991003

Details and patient eligibility

About

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.

Full 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

Enrollment: 22 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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22 participants in 4 patient groups, including a placebo group

PF-06648671 High dose group

Experimental group

Description:

subjects receive a single oral dose of PF-06648671 at 300 mg

Treatment:

Drug: PF-06648671

PF-06648671 Low dose group

Experimental group

Description:

Subjects receive a single oral dose of PF-06648671 lower than 300 mg dose

Treatment:

Drug: PF-06648671

Placebo group

Placebo Comparator group

Description:

Subjects receive matching placebo

Treatment:

Drug: Placebo

PF-06648671 Low dose group (2)

Experimental group

Description:

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

Treatment:

Drug: PF-06648671