NCT02871037 - Single Dose, Repeated Dose, and Conditional Food Effect Study of PF-05221304 in Healthy Subjects | Crick | Crick

Single Dose, Repeated Dose, and Conditional Food Effect Study of PF-05221304 in Healthy Subjects

Phase 1CompletedNCT02871037

Pfizer96 enrolled

Overview

The current study is the first clinical trial proposed with PF-05221304. It is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) following administration of single and repeated doses of PF-05221304 to healthy adult subjects. The study may also evaluate effect of food on PK of PF-05221304.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

96

Conditions

Interventions

PF-05221304DRUG

Single or repeated, escalating dose of PF-05221304

single or repeated dose of placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy males and female of non-childbearing potential; * Body Mass Index 17.5-30.5 kg/m2; * Body weight \>50 kg; 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

Locations (1)

New Haven Clinical Research Unit

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

Part 1: Number of Subjects experiencing an Adverse Event

Assessment by adverse event monitoring, 12 lead ECGs, telemetry, vital signs and clinical safety laboratory measurements. 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.

Time frame: Screening up to 28 days after last dose of study medication

Part 2: Number of Subjects experiencing an Adverse Event

Assessment by adverse event monitoring, 12 lead ECGs, telemetry, vital signs and clinical safety laboratory measurements. 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.

Time frame: Screening up to 28 days after last dose of study medication

Part 3: Maximum Observed Plasma Concentration (Cmax) for PF-05221304

Maximum Observed Plasma Concentration (Cmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose

Data from ClinicalTrials.gov

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Secondary Outcomes

Part 1:Maximum Observed Plasma Concentration (Cmax) for PF-05221304

Maximum Observed Plasma Concentration (Cmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose

Part 1: Time to Reach Maximum Observed Concentration for PF-05221304

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose

Part 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05221304

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose

Part 1: dose-normalized Cmax and AUClast for PF05221304

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose

Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] for PF-05221304 (as permitted)

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).

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose

Part 1: Plasma Decay Half-Life (t1/2) for PF-05221304 (as permitted)

Plasma Decay Half-Life (t1/2)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose

Part 1: Apparent Total Body Clearance (CL/F) for PF-05221304 (as permitted)

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 apparent total body 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.

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose

Part 1: Apparent Volume of Distribution (Vz/F) for PF-05221304 (as permitted)

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.

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose

Part 2: Single dose plasma parameters of Cmax for PF-05221304

Maximum Observed Plasma Concentration (Cmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Day 1

Part 2: Single-dose plasma parameters of Tmax for PF-05221304

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Day 1

Part 2: Single-dose plasma parameters of Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-05221304

Area under the concentration curve from time 0 to end of dosing interval (AUCtau)

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Day 1

Part 2: Multiple-dose plasma parameters of Cmax for PF-05221304

Maximum Observed Plasma Concentration (Cmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted)

Part 2: Multiple-dose plasma parameters of Tmax for PF-05221304

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted)

Part 2: Multiple-dose plasma parameters of AUCtau for PF-05221304

Area under the concentration curve from time 0 to end of dosing interval (AUCtau)

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted)

Part 2: Multiple-dose plasma parameters of Minimum Observed Plasma Trough Concentration (Cmin) for PF-05221304

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted)

Part 2: Multiple-dose plasma parameters of CL/F for PF-05221304

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 apparent total body 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.

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted)

Part 2: Multiple-dose plasma parameters of Vz/F for PF-05221304 (as permitted)

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.

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours on Day 1 and 7, and 0 hr on Day 2, Day 4, Day 8, Day 10, Day 13, Day 15, and Day 16 post dose

Part 2: Multiple-dose plasma parameters of Peak-trough ratio (PTR) for PF-05221304

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted)

Part 2: Multiple-dose plasma parameters of Observed accumulation ratio for Cmax (Rac(Cmax)) for PF-05221304

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted)

Part 2: Multiple-dose plasma parameters of Observed accumulation ratio (Rac(AUCtau))

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted)

Part 2: Multiple-dose plasma parameters of Plasma Decay Half-Life (t1/2) for PF-05221304 (as permitted)

Plasma Decay Half-Life (t1/2)

Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours on Day 1 and 7, and 0 hr on Day 2, Day 4, Day 8, Day 10, Day 13, Day 15, and Day 16 post dose

Part 3: Number of Subjects experiencing an Adverse Event

Assessment by adverse event monitoring, 12 lead ECGs, telemetry, vital signs and clinical safety laboratory measurements. 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.

Time frame: Screening up to 28 days after last dose of study medication