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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: PF-06427878; Drug: Placebo; Drug: PF-06427878; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / 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).; 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).
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).; 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).
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).; 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).
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).; 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).
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).; 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).
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 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).; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Amin NB, Carvajal-Gonzalez S, Purkal J, Zhu T, Crowley C, Perez S, Chidsey K, Kim AM, Goodwin B. Targeting diacylglycerol acyltransferase 2 for the treatment of nonalcoholic steatohepatitis. Sci Transl Med. 2019 Nov 27;11(520):eaav9701. doi: 10.1126/scitranslmed.aav9701.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: March 12, 2015
• First Submitted That Met QC Criteria: March 12, 2015
• First Posted (Estimate): March 18, 2015

Study Record Updates

• Last Update Posted (Estimate): March 2, 2016
• Last Update Submitted That Met QC Criteria: March 1, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Hyperlipidemia; Healthy Subjects; Lipid Metabolism Disorders; Metabolic Diseases; Multiple Ascending Dose
• Other Study ID Numbers: B7871002; 2015-000130-29 (EudraCT Number)