NCT02066909

Brief Summary

This study is designed to evaluate the safety and plasma concentrations of PF-06649751 in healthy volunteers following one or two times daily oral dosing of PF-06649751 for 14 days (Cohorts 1 - 4), 21 days (Cohort 5), or 28 days (Cohorts 6 - 8). Cohort 9 will dose Japanese healthy volunteers in a manner identical to Cohort 4 and is intended to bridge the safety/tolerability and PK data from the Western and Japanese populations.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
77

participants targeted

Target at P75+ for phase_1 healthy

Timeline
Completed

Started Feb 2014

Longer than P75 for phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2014

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

February 7, 2014

Completed
13 days until next milestone

First Posted

Study publicly available on registry

February 20, 2014

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2015

Completed
Last Updated

June 24, 2015

Status Verified

June 1, 2015

Enrollment Period

1.2 years

First QC Date

February 7, 2014

Last Update Submit

June 23, 2015

Conditions

Healthy

Keywords

pharmacokineticssafetytolerabilityhealthy volunteerssteady statemultiple dosesJapanese subjects

Outcome Measures

Primary Outcomes (19)

  • Supine and standing vital sign measurements

    Measurement of blood pressure and pulse rate

    Days 1 - 18 (Cohorts 1 - 4, 9), Days 1 - 25 (Cohort 5), Days 1 - 32 (Cohorts 6 - 8) and follow-up

  • Amount of unchanged drug excreted in urine relative to dose (Ae%)

    Day 14 (Cohorts 1 - 4, 9), Day 21 (Cohort 5), Day 28 (Cohorts 6 - 8)

  • Renal Clearance (CLR)

    Day 14 (Cohort 1 - 4, 9), Day 21 (Cohort 5) and Day 28 (Cohorts 6 - 8)

  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau)

    Day 1, Day 14 (Cohorts 1 - 4, 9), Day 1 and Day 21 (Cohort 5), Day 1 and Day 28 (Cohorts 6 - 8)

  • Maximum Observed Plasma Concentration (Cmax)

    Maximum plasma concentration

    Day 1, Day 7, Day 14 (Cohorts 1 - 4, 9), Day 1 and 21 (Cohort 5), Day 1 and 28 (Cohorts 6 - 8)

  • Time to Reach Maximum Observed Plasma Concentration (Tmax)

    Time for Cmax

    Day 1, Day 7, Day 14 (Cohorts 1 - 4, 9), Day 1 and 21 (Cohort 5), Day 1 and 28 (Cohorts 6 - 8)

  • Plasma Decay Half-Life (t1/2)

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

    Days 14 - 18 (Cohorts 1 - 4, 9), Days 21 - 25 (Cohort 5), Days 28 - 32 (Cohorts 6 - 8)

  • Apparent Oral Clearance (CL/F)

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

    Days 14 - 18 (Cohorts 1 - 4, 9), Days 21 - 25 (Cohort 5), Days 28 - 32 (Cohorts 6 - 8)

  • Apparent Volume of Distribution (Vz/F)

    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

    Days 14 - 18 (Cohorts 1 - 4, 9), Days 21 - 25 (Cohort 5), Days 28 - 32 (Cohorts 6 - 8)

  • Trough Concentration (Ctrough)

    Minimum concentration pre-dose

    Day 1 to 14 (Cohorts 1 - 4, 9), Day 1 to 21 (Cohort 5), Day 1 to 28 (Cohorts 6 - 8)

  • Ratio of accumulation for AUCtau (Rac AUCtau)

    Ratio of accumulation for AUCtau. Corrected for titrated doses.

    Day 1 and 14 (Cohorts 1 - 4, 9), Day 1 and 21 (Cohort 5), Day 1 and 28 (Cohorts 6 - 8)

  • Ratio of accumulation for Cmax (Rac Cmax)

    Ratio of accumulation for Cmax. Corrected for titrated doses.

    Day 1, Day 7 and Day 14 (Cohorts 1 - 4, 9), Day 1 and 21 (Cohort 5), Day 1 and 28 (Cohorts 6 - 8)

  • Peak-to-trough ratio (PTR)

    Peak-to-trough ratio at steady state

    Day 7 and Day 14 (Cohorts 1 - 4, 9), Day 21 (Cohort 5), Day 28 (Cohorts 6 - 8)

  • Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS)

    C-SSRS assessed whether participant experienced following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has subject engaged in non-suicidal self-injurious behavior").

    Day 0 and 14 (Cohorts 1 - 4, 9), Day 0 and 21 (Cohort 5), Day 0 and 28 (Cohort 6 - 8) and follow-up

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to \[study drug\] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.

    Days 1 - 18 (Cohorts 1 - 4, 9), Days 1 - 25 (Cohort 5), Days 1 - 32 (Cohorts 6 - 8) and follow-up

  • Electrocardiogram (ECG)

    Measurement of standard 12-lead ECG, single or triplicate

    Days 1 - 18 (Cohorts 1 - 4, 9), Days 1 - 25 (Cohort 5), Days 1 - 32 (Cohorts 6 - 8) and follow-up

  • Number of Participants With Laboratory Test Values of Potential Clinical Importance

    Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.

    Days 1 - 18 (Cohorts 1 - 4, 9), Days 1 - 25 (Cohort 5), Days 1 - 32 (Cohorts 6 - 8) and follow-up

  • Changes from baseline in total cholesterol, High Density Lipoprotein (HDL) cholesterol, Low Density Lipoprotein (LDL) cholesterol, triglycerides

    Day 1 and Day 14 (Cohorts 1 - 4, 9), Day 1 and 21 (Cohort 5), Day 1 and 28 (Cohorts 6 - 8)

  • Amount of unchanged drug excreted in urine relative to dose (Ae)

    Calculated from urinary volumes and concentration

    Day 14 (Cohorts 1 - 4, 9), Day 21 (Cohort 5), Day 28 (Cohorts 6 - 8)

Secondary Outcomes (1)

  • Metabolite Scouting

    Day 1 (Cohorts 1 - 9) , Day 14 (Cohorts 1 - 4, 9), Day 21 (Cohort 5), Day 28 (Cohorts 6 - 8)

Study Arms (9)

Cohort 1

EXPERIMENTAL

Dosing in healthy Western subjects.

Drug: 0.15 mg PF-06649751

Cohort 2

EXPERIMENTAL

Dosing in healthy Western subjects.

Drug: 0.5 mg PF-06649751

Cohort 3

EXPERIMENTAL

Dosing in healthy Western subjects.

Drug: 0.5 mg PF-06649751

Cohort 4

EXPERIMENTAL

Dosing in healthy Western subjects.

Drug: 1.5 mg PF-06649751

Cohort 5

EXPERIMENTAL

Dosing in healthy Western subjects.

Drug: 1.5 mg PF-06649751 21 Days

Cohort 6

EXPERIMENTAL

Dosing in healthy Western subjects.

Drug: 3.0 mg PF-06649751

Cohort 7

EXPERIMENTAL

Dosing in healthy Western subjects.

Drug: 5.0 mg PF-06649751

Optional Cohort 8

EXPERIMENTAL

Dosing in healthy Western subjects. Cohort may not be conducted.

Drug: 8.0 mg PF-06649751

Cohort 9

EXPERIMENTAL

Dosing in healthy Japanese subjects.

Drug: 1.5 mg PF-06649751 in healthy Japanese subjects

Interventions

0.15 mg PF-06649751DRUG

Oral dosing of 0.15 mg PF-06649751 extemporaneously-prepared solution given once-daily for 14 days.

Cohort 1
0.5 mg PF-06649751DRUG

Oral dosing of 0.5 mg PF-06649751 extemporaneously-prepared solution given once-daily for 14 days.

Cohort 2
1.5 mg PF-06649751DRUG

Oral dosing of tablets up to 1.5 mg PF-06649751 given once-daily for 14 days.

Cohort 4
1.5 mg PF-06649751 21 DaysDRUG

Oral dosing of tablets up to 1.5 mg PF-06649751 given once-daily for 21 days.

Cohort 5
3.0 mg PF-06649751DRUG

Oral dosing of tablets up to 3.0 mg PF-06649751 given once-daily for 28 days.

Cohort 6
5.0 mg PF-06649751DRUG

Oral dosing of tablets up to 5.0 mg PF-06649751 given once-daily for 28 days.

Cohort 7
8.0 mg PF-06649751DRUG

Oral dosing of tablets up to 8.0 mg PF-06649751 given once-daily for 28 days.

Optional Cohort 8
1.5 mg PF-06649751 in healthy Japanese subjectsDRUG

Oral dosing of tablets up to 1.5 mg PF-06649751 given once-daily for 14 days given in healthy Japanese subjects.

Cohort 9

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy males and/or female subjects of non childbearing potential between the ages of 18 and 55 years, inclusive (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests).
  • Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs).
  • Cohort 9 only: Japanese subjects must have four biologic Japanese grandparents who were born in Japan.

You may not qualify if:

  • 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).
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Links

Study Officials

  • Pfizer CT.gov Call Center

    Pfizer

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 7, 2014

First Posted

February 20, 2014

Study Start

February 1, 2014

Primary Completion

April 1, 2015

Study Completion

April 1, 2015

Last Updated

June 24, 2015

Record last verified: 2015-06

Locations

US(1)