A Multiple Dose Study Of PF-06678552 In Healthy Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT02079922
First received: March 4, 2014
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

PF-06678552 is a new compound proposed for the treatment of hypercholesteremia. The primary purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of PF-06678552 in healthy subjects.


Condition Intervention Phase
Healthy
Drug: PF-06678552
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study To Assess The Safety, Tolerability, And Pharmacokinetics Of PF-06678552 After Administration Of Multiple Escalating Oral Doses In Healthy Adult Subjects

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Assessment of adverse events (AEs), clinical laboratory tests, vital signs (including blood pressure and pulse rate), and cardiac conduction intervals as assessed by 12 lead ECG. [ Time Frame: 0 to 24 days post dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 on day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve during the dosing interval (AUCtau) for PF-06644927 on day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve during the dosing interval (AUCtau) for PF-06644927 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve during the dosing interval (AUCtau) for PF-06644927 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) for PF-06644927 on day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) for PF-06644927 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) for PF-06644927 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 on day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) for PF-06644927 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48 hours post dose ] [ Designated as safety issue: No ]
  • Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06644927 on day 7 relative to day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06644927 on day 14 relative to day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06644927 on day 7 relative to day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06644927 on day 14 relative to day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Amount of PF-06644927 excreted in urine (Ae) on day 14 [ Time Frame: 0-12 hours post dose ] [ Designated as safety issue: No ]
  • Percent of dose excreted in urine as PF-06644927 (Ae%) on day 14 [ Time Frame: 0-12 hours post dose ] [ Designated as safety issue: No ]
  • Renal clearance of PF-06644927 (CLr) on day 14 [ Time Frame: 0-12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 on day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve during the dosing interval (AUCtau) for PF-06678552 on day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve during the dosing interval (AUCtau) for PF-06678552 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve during the dosing interval (AUCtau) for PF-06678552 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) for PF-06678552 on day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) for PF-06678552 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) for PF-06678552 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06678552 on day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06678552 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) for PF-06678552 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48 hours post dose ] [ Designated as safety issue: No ]
  • Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06678552 on day 7 relative to day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06678552 on day 14 relative to day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06678552 on day 7 relative to day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06678552 on day 14 relative to day 1 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
  • Apparent Oral Clearance (CL/F) of PF-06678552 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
    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. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  • Apparent Oral Clearance (CL/F) of PF-06678552 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
    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. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  • Apparent Volume of Distribution (Vz/F) of PF-06678552 on day 7 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
    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.

  • Apparent Volume of Distribution (Vz/F) of PF-06678552 on day 14 [ Time Frame: 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose ] [ Designated as safety issue: No ]
    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.


Enrollment: 38
Study Start Date: March 2014
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Single dose level of PF-06678552 or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
Drug: PF-06678552
PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.
Drug: Placebo
PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.
Experimental: Cohort 2
Single dose level of PF-06678552 or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
Drug: PF-06678552
PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.
Drug: Placebo
PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.
Experimental: Cohort 3
Single dose level of PF-06678552 or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
Drug: PF-06678552
PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.
Drug: Placebo
PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.
Experimental: Cohort 4
Single dose level of PF-06678552 or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
Drug: PF-06678552
PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.
Drug: Placebo
PF-06678552 or placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days.
Experimental: Cohort 5
Single dose level of PF-06678552 or placebo will be provided either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
Drug: PF-06678552
PF-06678552 or placebo will be administered as an extemporaneously prepared solution either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days.
Drug: Placebo
PF-06678552 or placebo will be administered as an extemporaneously prepared solution either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days.
Experimental: Cohort 6
Single dose level of PF-06678552 or placebo will be provided either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.
Drug: PF-06678552
PF-06678552 or placebo will be administered as an extemporaneously prepared solution either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days.
Drug: Placebo
PF-06678552 or placebo will be administered as an extemporaneously prepared solution either once daily (QD), every 12 hours (Q12H), or every 8 hours (Q8H) for 14 days.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male and/or female subjects of non-childbearing potential.
  • Body Mass Index (BMI) of 18 to 30.5 kg/m2; and a total body weight >50 kg
  • Low density lipoprotein cholesterol between 115 mg/dL and 190 mg/dL

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 time of dosing)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02079922

Locations
Belgium
Pfizer Investigational Site
Brussels, Belgium, B-1070
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02079922     History of Changes
Other Study ID Numbers: B7611002
Study First Received: March 4, 2014
Last Updated: July 29, 2014
Health Authority: Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Pfizer:
Multiple Ascending Dose
healthy subjects
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 20, 2014