Clinical trial NCT02316756: A Single Ascending Dose Study To Evaluate Safety And Pharmacokinetics Of Compound PF-06648671 In Healthy Subjects
Official title: A Phase 1, Randomized, Double-blind, Sponsor-open, Placebo-controlled First-in-human Trial To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-06648671 After Administration Of Single Ascending Doses To Fasted And Fed Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Phase 1, Single-Dose Escalation, Double Blind, Placebo-Controlled, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, PF-06648671, Plasma Abeta
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-12-15
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This is first in human (FIH), double-blind, sponsor open, placebo-control trial to examine the safety, tolerability, pharmacokinetics and pharmacodynamics following a single ascending doses of PF-06648671 in healthy subjects.


Eligibility 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 drg 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)
* 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 judgement of the investigator, would make the subject inappropriate for entry into this study.

Primary outcomes:
measure: Number of participants with AEs and SAEs
timeFrame: 0-6 weeks
measure: Supine vital sign measurement
timeFrame: 0-6 weeks
measure: Electrocardiogram (ECG)
timeFrame: 0-6 weeks
measure: Number of participants with lab test values of potential clinical importance
timeFrame: 0-6 weeks
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 0-72 hours post dose
measure: Area Under the Curve From Time Zeor to Last Quantifiable Concentration (AUClast)
timeFrame: 0-72 hours post dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
timeFrame: 0-72 hours post dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 0-72 hours post dose
measure: Plasma Decay Half-life (t1/2)
timeFrame: 0-72 hours post dose
measure: Apparent Oral Clearance (CL/F)
timeFrame: 0-72 hours post dose
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 0-72 hours post dose
measure: Plasma Cmax ratio under fed vs fasted conditions
timeFrame: 0-72 hours post dose
measure: Plasma AUClast ratio under fed vs fasted condition
timeFrame: 0-72 hours post dose
measure: Plasma AUCinf ratio under fed vs fasted conditions
timeFrame: 0-72 hours post dose
measure: Plasma Abeta42 Maximum change from baseline
timeFrame: 0-72 hours post dose
measure: Plasma Abeta42, Area Under the Effect Curve from Time Zero to Last Quantifiable Concentration (AUEC)
timeFrame: 0-72 hours post dose
measure: Plasma Abeta42, Time to Reach Maximum Observed Effect (Tmax)
timeFrame: 0-72 hours post-dose
measure: Plasma Abeta40 Maximum change from baseline
timeFrame: 0-72 hours post dose
measure: Plasma Abeta40, Area Under the Effect Curve from Time Zero to Last Quantifiable Concentration (AUEC)
timeFrame: 0-72 hours post dose
measure: Plasma Abeta40, Time to Reach Maximum Observed Effect (Tmax)
timeFrame: 0-72 hours post-dose
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
affiliation: Pfizer
name: Laure Mendes da Costa, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ahn JE, Carrieri C, Dela Cruz F, Fullerton T, Hajos-Korcsok E, He P, Kantaridis C, Leurent C, Liu R, Mancuso J, Mendes da Costa L, Qiu R. Pharmacokinetic and Pharmacodynamic Effects of a gamma-Secretase Modulator, PF-06648671, on CSF Amyloid-beta Peptides in Randomized Phase I Studies. Clin Pharmacol Ther. 2020 Jan;107(1):211-220. doi: 10.1002/cpt.1570. Epub 2019 Sep 11.