A Single Ascending Dose Study To Evaluate Safety And Pharmacokinetics Of Compound PF-06648671 In Healthy Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: PF-06648671; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Doses Cohort 1; subjects receive 3 active doses and one placebo	Drug: PF-06648671; Experimental Pfizer compound which will be dosed as oral suspension; Drug: Placebo; Placebo which will be given as oral suspension
Experimental: Single Ascending Doses Cohort 2; subjects receive 3 doses and one placebo	Drug: PF-06648671; Experimental Pfizer compound which will be dosed as oral suspension; Drug: Placebo; Placebo which will be given as oral suspension
Experimental: Cohort 3; optional cohort	Drug: PF-06648671; Experimental Pfizer compound which will be dosed as oral suspension; Drug: Placebo; Placebo which will be given as oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 occurences of an AE within a category will be counted once within the category	0-6 weeks
Supine vital sign measurement	Measurement of blood pressure and pulse rate	0-6 weeks
Electrocardiogram (ECG)	Measurement of standard 12-lead ECG, single or triplicate	0-6 weeks
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	0-6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax)	0-72 hours post dose
Area Under the Curve From Time Zeor to Last Quantifiable Concentration (AUClast)	0-72 hours post dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)	0-72 hours post dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0-72 hours post dose
Plasma Decay Half-life (t1/2)	0-72 hours post dose
Apparent Oral Clearance (CL/F)	0-72 hours post dose
Apparent Volume of Distribution (Vz/F)	0-72 hours post dose
Plasma Cmax ratio under fed vs fasted conditions	0-72 hours post dose
Plasma AUClast ratio under fed vs fasted condition	0-72 hours post dose
Plasma AUCinf ratio under fed vs fasted conditions	0-72 hours post dose
Plasma Abeta42 Maximum change from baseline	0-72 hours post dose
Plasma Abeta42, Area Under the Effect Curve from Time Zero to Last Quantifiable Concentration (AUEC)	0-72 hours post dose
Plasma Abeta42, Time to Reach Maximum Observed Effect (Tmax)	0-72 hours post-dose
Plasma Abeta40 Maximum change from baseline	0-72 hours post dose
Plasma Abeta40, Area Under the Effect Curve from Time Zero to Last Quantifiable Concentration (AUEC)	0-72 hours post dose
Plasma Abeta40, Time to Reach Maximum Observed Effect (Tmax)	0-72 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Principal Investigator: Laure Mendes da Costa, MD, Pfizer

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: December 10, 2014
• First Submitted That Met QC Criteria: December 10, 2014
• First Posted (Estimate): December 15, 2014

Study Record Updates

• Last Update Posted (Estimate): June 9, 2015
• Last Update Submitted That Met QC Criteria: June 8, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Phase 1, Single-Dose Escalation, Double Blind, Placebo-Controlled, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, PF-06648671, Plasma Abeta
• Other Study ID Numbers: B7991001; 2014-004394-17 (EudraCT Number)