Single Dose Study of PF-06815345 in Healthy Subjects

A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess Safety, Tolerability, And Pharmacokinetics Of Single Escalating Oral Doses Of Pf-06815345, As Well As Characterize The Pharmacokinetics Of Two Formulations And Effect Of Food On Pharmacokinetics Of One Formulation Of Pf-06815345 Administered To Healthy Adult Subjects

The current study is the first clinical trial proposed with PF-06815345. It is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) following administration of single oral doses of PF-06815345 to healthy adult subjects.

Study Overview

• Status: Terminated
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Other: Placebo; Drug: PF-06815345; Drug: PF-06815345

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 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 males and female of non-childbearing potential;
• Age of 18-55, inclusive;
• Body Mass Index 17.5-34.9 kg/m2, inclusive;
• Body weight >50 kg;
• Not on any prescription or non-prescription drugs within 7 days or 5 half-lives prior to first dose.

Exclusion Criteria:

- Evidence of history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergises, 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
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1_Cohort 1_Active; Single ascending dose of PF-06815345	Drug: PF-06815345; PF-06815345 will be administered as a liquid dosage formulation; Drug: PF-06815345; PF-06815345 will be administered as either solid dosage formulation or liquid dosage formulation
Placebo Comparator: Part 1_Cohort 1_Placebo; Single dose of placebo	Other: Placebo; Placebo
Experimental: Part 1_Cohort 2_Active; Single ascending dose of PF-06815345	Drug: PF-06815345; PF-06815345 will be administered as a liquid dosage formulation; Drug: PF-06815345; PF-06815345 will be administered as either solid dosage formulation or liquid dosage formulation
Placebo Comparator: Part 1_Cohort 2_Placebo; Single dose of placebo	Other: Placebo; Placebo
Experimental: Part 2; Single dose of solid dosage formulation (test) versus liquid dosage formulation (reference) of PF-06815345	Drug: PF-06815345; PF-06815345 will be administered as a liquid dosage formulation; Drug: PF-06815345; PF-06815345 will be administered as either solid dosage formulation or liquid dosage formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment Emergent Treatment-Related Adverse Events (AEs)	Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Drug was assessed by the investigator (Yes/No). Subjects with multiple occurrences of an AE within a category were counted once within the category.	Baseline (Day 0) up to 28 days after last dose of study medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06815345	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] for PF-06815345	AUC (0-infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-infinity). It is obtained from AUC (0-t) plus AUC (t-infinity).	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Maximum Observed Plasma Concentration (Cmax) for PF-06815345	Maximum Observed Plasma Concentration (Cmax)	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Time to Reach Maximum Observed Concentration for PF-06815345	Time to Reach Maximum Observed Plasma Concentration (Tmax)	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Plasma Decay Half-Life (t1/2) for PF-06815345	Plasma Decay Half-Life (t1/2)	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Apparent Oral Clearance (CL/F) for PF-06815345	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. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Apparent Volume of Distribution (Vz/F) for PF-06815345	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.	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for the metabolite (PF-06811701)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] for metabolite (PF-06811701)	AUC (0-infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-infinity). It is obtained from AUC (0-t) plus AUC (t-infinity).	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Maximum Observed Plasma Concentration (Cmax) for metabolite (PF-06811701)	Maximum Observed Plasma Concentration (Cmax)	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Time to Reach Maximum Observed Concentration for metabolite (PF-06811701)	Time to Reach Maximum Observed Plasma Concentration (Tmax)	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose
Plasma Decay Half-Life (t1/2) for metabolite (PF-06811701)	Plasma Decay Half-Life (t1/2)	0, 0.5, 1, 2, 3, 4, 6, 10, 14, 24, and 48 hours post dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: November 17, 2015
• First Submitted That Met QC Criteria: January 11, 2016
• First Posted (Estimate): January 13, 2016

Study Record Updates

• Last Update Posted (Actual): September 28, 2018
• Last Update Submitted That Met QC Criteria: September 26, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Dyslipidemia; Healthy subjects; Hyperlipidemia; Single Ascending Dose
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: C0281001; 2015-003935-36 (EudraCT Number)