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

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ClinicalTrials.gov Identifier: NCT02407353
Recruitment Status : Completed
First Posted : April 2, 2015
Last Update Posted : March 22, 2016
Sponsor:
Information provided by (Responsible Party):
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.

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 Type : Interventional  (Clinical Trial)
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 : October 2015
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

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




Primary Outcome Measures :
  1. CSF Aβ40 and Aβ42 concentration at maximum change from baseline [ Time Frame: 0-36 hours postdose ]

Secondary Outcome Measures :
  1. Number of participants with AEs and SAEs [ Time Frame: 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

  2. supine vital sign [ Time Frame: 0-2 weeks ]
    Measurement of supine vital signs

  3. Electrocardiogram (ECG) [ Time Frame: 0-2 weeks ]
    Measurement of standard 12-lead ECG (single)

  4. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0-72 hours postdose ]
  5. Area Under the Curve from Time Zero to Last Quantifiable Plasma Concentration (AUClast) [ Time Frame: 0-72 hours postdose ]
  6. Area Under the Curve From Time Zero to Extrapolated Infinite Time in Plasma (AUCinf) [ Time Frame: 0-72 hours postdose ]
  7. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0-72 hours postdose ]
  8. Plasma Decay Half-life (t1/2) [ Time Frame: 0-72 hours postdose ]
  9. Apparent Oral Clearance (CL/F) [ Time Frame: 0-72 hours postdose ]
  10. Apparent Volume of Distribution (Vz/F)) [ Time Frame: 0-72 hours postdose ]
  11. Maximum Observed CSF Concentration (CSF Cmax) [ Time Frame: 0-36 hours postdose ]
  12. Area Under the Curve from Time Zero to Last Quantifiable Concentration in CSF (CSF AUClast) [ Time Frame: 0-36 hours postdose ]
  13. Area Under the Curve From Time Zero to Extrapolated Infinite Time in CSF (CSF AUCinf) [ Time Frame: 0-36 hours postdose ]
  14. CSF Decay Half-life (CSF t1/2) [ Time Frame: 0-36 hours postdose ]
  15. Plasma Aβ40, Aβ42 and Aβtotal [ Time Frame: 0-72 hours postdose ]
    Plasma Aβ40, Aβ42 and Aβtotal if possible

  16. CSF Aβ37, Aβ38 and Aβtotal Concentration [ Time Frame: 0-36 hours postdose ]
  17. Number of participants with lab test values of potential clinical importance [ Time Frame: 0-2 weeks ]
    Pre-defined criteria were established for each lab test to identify potential clinical importance



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02407353


Locations
United States, California
California Clinical Trials Medical Group, Inc.
Glendale, California, United States, 91206
Glendale Adventist Medical Center
Glendale, California, United States, 91206
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02407353     History of Changes
Other Study ID Numbers: B7991003
First Posted: April 2, 2015    Key Record Dates
Last Update Posted: March 22, 2016
Last Verified: March 2016

Keywords provided by Pfizer:
Phase 1
Double blind
Placebo-Controlled
Parallel Design
CSF Aβ Concentrations
PF-06648671