Clinical trial NCT02391623: A Multiple Oral Doses Study Of PF-06427878 In Healthy Adult Subjects
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Multiple Ascending Dose
Healthy Subjects
Hyperlipidemia
Lipid Metabolism Disorders
Metabolic Diseases
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-03-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Assessment of adverse events (AEs).
timeFrame: 0-25 days
measure: Assessment of clinical laboratory tests.
timeFrame: 0-25 days
measure: Assessment of vital signs (including blood pressure and pulse rate).
timeFrame: 0-25 days
measure: Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG).
timeFrame: 0-25 days
Secondary outcomes:
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: Maximum Observed Plasma Concentration (Cmax) for PF-06427878 on day 14
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12 hours post dose
measure: 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
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: Accumulation ratio for Area Under the Curve during the dosing interval (Rac(AUCtau)) for PF-06427878 on day14 relative to day 1
timeFrame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post dose
measure: 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
timeFrame: 0- tau hours post dose
measure: 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
timeFrame: 0- tau hours post dose
measure: 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
timeFrame: 0- tau hours post dose
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.