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Completed

NCT Number: NCT02066909

A Study To Observe Safety And Blood Concentrations Of PF-06649751 During And Following The Oral Administration Of Multiple Doses Of PF-06649751 In Healthy Adult Western and Japanese Volunteers

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.

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Key information

Conditions

Healthy

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

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).
  • 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.

Treatment and study plan

0.15 mg PF-06649751

Drug

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

0.5 mg PF-06649751

Drug

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

1.5 mg PF-06649751

Drug

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

1.5 mg PF-06649751 21 Days

Drug

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

3.0 mg PF-06649751

Drug

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

5.0 mg PF-06649751

Drug

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

8.0 mg PF-06649751

Drug

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

1.5 mg PF-06649751 in healthy Japanese subjects

Drug

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

Primary outcomes

  1. Supine and standing vital sign measurements

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

    Measurement of blood pressure and pulse rate

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

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

  3. Renal Clearance (CLR)

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

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

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

  5. Maximum Observed Plasma Concentration (Cmax)

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

    Maximum plasma concentration

  6. Time to Reach Maximum Observed Plasma Concentration (Tmax)

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

    Time for Cmax

  7. Plasma Decay Half-Life (t1/2)

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

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

  8. Apparent Oral Clearance (CL/F)

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

    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.

  9. Apparent Volume of Distribution (Vz/F)

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

    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.

  10. Trough Concentration (Ctrough)

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

    Minimum concentration pre-dose

  11. Ratio of accumulation for AUCtau (Rac AUCtau)

    Time frame: 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 AUCtau. Corrected for titrated doses.

  12. Ratio of accumulation for Cmax (Rac Cmax)

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

    Ratio of accumulation for Cmax. Corrected for titrated doses.

  13. Peak-to-trough ratio (PTR)

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

    Peak-to-trough ratio at steady state

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

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

    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").

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

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

    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.

  16. Electrocardiogram (ECG)

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

    Measurement of standard 12-lead ECG, single or triplicate

  17. Number of Participants With Laboratory Test Values of Potential Clinical Importance

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

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

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

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

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

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

    Calculated from urinary volumes and concentration

Secondary outcomes

  1. Metabolite Scouting

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

    Identification of metabolites from blood and urine samples.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

A Phase 1, Double Blind, Sponsor Open, Randomized, Placebo Controlled, Dose Escalation, Parallel Group Study To Investigate The Safety, Tolerability And Pharmacokinetics Of Repeat Doses Of Pf-06649751 In Healthy Western And Japanese Subjects

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Feb 20, 2014
Registry last updated
Jun 24, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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