A Multiple Dose Study Of PF-06678552 In Healthy Subjects

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT02079922

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

9.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Healthy	Drug: PF-06678552 Drug: Placebo Drug: PF-06678552 Drug: Placebo Drug: PF-06678552 Drug: Placebo Drug: PF-06678552 Drug: Placebo Drug: PF-06678552 Drug: Placebo Drug: PF-06678552 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, 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

Study Start Date :

Mar 1, 2014

Actual Primary Completion Date :

Jul 1, 2014

Actual Study Completion Date :

Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

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. [0 to 24 days post dose]

Secondary Outcome Measures

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 on day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 on day 7 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 on day 14 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve during the dosing interval (AUCtau) for PF-06644927 on day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve during the dosing interval (AUCtau) for PF-06644927 on day 7 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve during the dosing interval (AUCtau) for PF-06644927 on day 14 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Maximum Observed Plasma Concentration (Cmax) for PF-06644927 on day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Maximum Observed Plasma Concentration (Cmax) for PF-06644927 on day 7 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Maximum Observed Plasma Concentration (Cmax) for PF-06644927 on day 14 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 on day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 on day 7 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 on day 14 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Plasma Decay Half-Life (t1/2) for PF-06644927 on day 14 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48 hours post dose]
Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06644927 on day 7 relative to day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06644927 on day 14 relative to day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06644927 on day 7 relative to day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06644927 on day 14 relative to day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Amount of PF-06644927 excreted in urine (Ae) on day 14 [0-12 hours post dose]
Percent of dose excreted in urine as PF-06644927 (Ae%) on day 14 [0-12 hours post dose]
Renal clearance of PF-06644927 (CLr) on day 14 [0-12 hours post dose]
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 on day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 on day 7 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 on day 14 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve during the dosing interval (AUCtau) for PF-06678552 on day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve during the dosing interval (AUCtau) for PF-06678552 on day 7 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Area Under the Curve during the dosing interval (AUCtau) for PF-06678552 on day 14 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Maximum Observed Plasma Concentration (Cmax) for PF-06678552 on day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Maximum Observed Plasma Concentration (Cmax) for PF-06678552 on day 7 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Maximum Observed Plasma Concentration (Cmax) for PF-06678552 on day 14 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06678552 on day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06678552 on day 7 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Plasma Decay Half-Life (t1/2) for PF-06678552 on day 14 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48 hours post dose]
Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06678552 on day 7 relative to day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06678552 on day 14 relative to day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06678552 on day 7 relative to day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUC)) for PF-06678552 on day 14 relative to day 1 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
Apparent Oral Clearance (CL/F) of PF-06678552 on day 7 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
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 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
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 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
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 [0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 hours post dose]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)