A Multiple Oral Doses Study Of PF-06427878 In Healthy Adult Subjects

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT02391623

Collaborator

(none)

Enrollment

Location

Arms

11.1

Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

PF-06427878 is a new compound proposed for the treatment of hyperlipidemia. The primary purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple oral doses of PF-06427878 in healthy adult subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: PF-06427878 Drug: Placebo Drug: PF-06427878 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

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 Multiple Escalating Oral Doses Of Pf-06427878 Co Administered With And Without Food In Healthy Adult Subjects

Study Start Date :

Mar 1, 2015

Actual Primary Completion Date :

Feb 1, 2016

Actual Study Completion Date :

Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Single dose level of PF-06427878 at 5 mg or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.	Drug: PF-06427878 PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8). Drug: Placebo Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).
Experimental: Cohort 2 Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 1 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.	Drug: PF-06427878 PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8). Drug: Placebo Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).
Experimental: Cohort 3 Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 2 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.	Drug: PF-06427878 PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8). Drug: Placebo Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).
Experimental: Cohort 4 Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 3 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.	Drug: PF-06427878 PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8). Drug: Placebo Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).
Experimental: Cohort 5 Single dose level of PF-06427878 at a dose no more than 3.5-fold increase from Cohort 4 or placebo every 8 hours (Q8H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.	Drug: PF-06427878 PF-06427878 will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=8). Drug: Placebo Placebo will be administered as an extemporaneously prepared solution every 8 hours for 14 days (n=2).
Experimental: Cohort 6 Single dose level of PF-06427878 (with the same total daily dose as Cohort 5) or placebo every 12 hours (Q12H) for 14 days to investigate the safety, tolerability, and pharmacokinetics.	Drug: PF-06427878 PF-06427878 will be administered as an extemporaneously prepared solution every 12 hours for 14 days (n=8). Drug: Placebo Placebo will be administered as an extemporaneously prepared solution every 12 hours for 14 days (n=2).

Outcome Measures

Primary Outcome Measures

Assessment of adverse events (AEs). [0-25 days]
Assessment of clinical laboratory tests. [0-25 days]
Assessment of vital signs (including blood pressure and pulse rate). [0-25 days]
Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG). [0-25 days]

Secondary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Maximum Observed Plasma Concentration (Cmax) for PF-06427878during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Maximum Observed Plasma Concentration (Cmax) for PF-06427878 on day 14 [0, 1, 2, 3, 4, 6, 8, 12 hours post dose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Plasma Decay Half-Life (t1/2) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Apparent Volume of Distribution (Vz/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Apparent Oral Clearance (CL/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Minimum Observed Plasma Concentration (Cmin) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Peak:Trough ratio of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1 [0, 1, 2, 3, 4, 6, 8, 12 hours post dose]
Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUCtau)) for PF-06427878 on day14 relative to day 1 [0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose]
Amount of PF-06427878 excreted in urine (Ae) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0- tau hours post dose]
Percent of dose excreted in urine as PF-06427878 (Ae%) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0- tau hours post dose]
Renal clearance of PF-06427878 (CLr) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14 [0- tau hours post dose]

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 17.5 to 35.4 kg/m2; and a total body weight >50 kg
Subjects with fasting TG level of >=90 mg/dL and <=500 mg/dL following an overnight fast
Subjects with low density lipoprotein cholesterol between 115 mg/dL and 190 mg/dL following an overnight fast

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).