A First in Human Study to Evaluate Safety, Tolerability, and Pharmacology of PF-06826647 in Healthy Subjects and Subjects With Plaque Psoriasis

A PHASE 1, WITHIN COHORT, RANDOMIZED, DOUBLE BLIND, THIRD-PARTY OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE DOSE ESCALATION, PARALLEL GROUP STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-06826647 IN HEALTHY SUBJECTS AND SUBJECTS WITH PLAQUE PSORIASIS

This first in human study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-06826647 in healthy subjects and subjects with plaque psoriasis.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: PF-06826647 tablet; Other: Placebo tablet; Drug: PF-06826647 oral suspension; Other: Placebo oral solution/suspension

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC

Participation Criteria

Eligibility Criteria

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

Description

Healthy Participants:

Inclusion Criteria:

• Healthy male subjects between ages of 18-55 years
• Healthy female subjects of non-childbearing potential between the ages of 18-55 years
• Body Mass Index (BMI) of 17.5 to 30.5kg/m2; and a total body weight >50kg (110lbs).
• No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
• (Optional) Japanese subjects who have four Japanese biologic grandparents born in Japan

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)
• Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential
• Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product
• Have a clinically significant infection currently or within 6 months of first dose of study drug

Psoriasis Participants:

Inclusion Criteria:

• Healthy male subjects between ages of 18-65 years
• Healthy female subjects of non-childbearing potential between the ages of 18-65 years
• Have a diagnosis of plaque psoriasis for at least 6 months prior to first study dose
• Have plaque-type psoriasis covering at least 15% of total body surface area (BSA) at Day-1(prior to randomization in the study
• No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)

Exclusion Criteria:

• Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis
• Have a clinically significant infection currently or within 6 months of first dose of study drug, or a history of chronic or recurrent infectious disease
• Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential
• Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo tablet	Other: Placebo tablet; Matching placebo tablet
EXPERIMENTAL: PF-06826647 tablet	Drug: PF-06826647 tablet; PF-06826647 tablet for oral administration
EXPERIMENTAL: PF-06826647 oral suspension	Drug: PF-06826647 oral suspension; PF-06826647 suspension for oral administration (oral suspension to be administered to the 3mg starting dose cohort only)
PLACEBO_COMPARATOR: Placebo oral solution/suspension	Other: Placebo oral solution/suspension; placebo oral solution for the single ascending dose, first cohort only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Single Ascending Dose [SAD] Period)	Maximum absolute values and changes from baseline for vital signs (for supine systolic/diastolic blood pressure [BP] and supine pulse rate [PR]) were summarized descriptively by treatment. Numbers of participants meeting the categorical criteria were provided. Number of participants in PBO SAD cohorts = number of participants in [PBO SAD (3mg, 10mg)] cohorts + number of participants in [PBO SAD -> PBO QD MAD] cohorts.	Baseline up to Day 8
Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Multiple Ascending Dose [MAD] Period)	Maximum absolute values and changes from baseline for vital signs (for supine systolic/diastolic blood pressure and supine pulse rate) were summarized descriptively by treatment. Numbers of participants meeting the categorical criteria were provided.	Baseline up to Day 28
Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)	Maximum absolute values and changes from baseline for vital signs (for supine systolic/diastolic blood pressure and supine pulse rate) were summarized descriptively by treatment. Numbers of participants meeting the categorical criteria were provided.	Baseline up to Day 56
Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (SAD Period)	Physical examinations were conducted by a physician, trained physician assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision. Number of participants in PBO SAD cohorts = number of participants in [PBO SAD (3mg, 10mg)] cohorts + number of participants in [PBO SAD -> PBO QD MAD] cohorts.	Baseline up to Day 8
Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (MAD Period)	Physical examinations were conducted by a physician, trained physician assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.	Baseline up to Day 28
Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)	Physical examinations were conducted by a physician, trained physician assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.	Baseline up to Day 56
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria (SAD Period)	ECG endpoints and changes from baseline (QTcF, PR and QRS) were summarized descriptively by cohort and treatment using pre-defined categories. Numbers of participants meeting the categorical criteria were provided. All planned and unplanned post-dose time points were counted in these categorical summaries. Categorical summarization criteria for ECG were as follows: 1) QTcF maximum absolute value ≥450 and <480 millisecond (msec), ≥480 and <500 msec. ≥500 msec; 2) QTcF maximum increase ≥30 and <60 msec, ≥60 msec; 3) PR maximum absolute value ≥300 msec; 4) PR maximum increases from baseline ≥25% if baseline >200 msec, ≥50% if baseline ≤200 msec; 5) QRS maximum absolute value ≥140 msec; 6) QRS maximum increase from baseline ≥50%. Number of participants in PBO SAD cohorts = number of participants in [PBO SAD (3mg, 10mg)] cohorts + number of participants in [PBO SAD -> PBO QD MAD] cohorts.	Baseline up to Day 8
Number of Participants With ECG Data Meeting Pre-Specified Criteria (MAD Period)	ECG endpoints and changes from baseline (QTcF, PR and QRS) were summarized descriptively by cohort and treatment using pre-defined categories. Numbers of participants meeting the categorical criteria were provided. All planned and unplanned post-dose time points were counted in these categorical summaries. Categorical summarization criteria for ECG were as follows: 1) QTcF maximum absolute value ≥450 and <480 millisecond (msec), ≥480 and <500 msec. ≥500 msec; 2) QTcF maximum increase ≥30 and <60 msec, ≥60 msec; 3) PR maximum absolute value ≥300 msec; 4) PR maximum increases from baseline ≥25% if baseline >200 msec, ≥50% if baseline ≤200 msec; 5) QRS maximum absolute value ≥140 msec; 6) QRS maximum increase from baseline ≥50%.	Baseline up to Day 28
Number of Participants With ECG Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)	ECG endpoints and changes from baseline (QTcF, PR and QRS) were summarized descriptively by cohort and treatment using pre-defined categories. Numbers of participants meeting the categorical criteria were provided. All planned and unplanned post-dose time points were counted in these categorical summaries. Categorical summarization criteria for ECG were as follows: 1) QTcF maximum absolute value ≥450 and <480 millisecond (msec), ≥480 and <500 msec. ≥500 msec; 2) QTcF maximum increase ≥30 and <60 msec, ≥60 msec; 3) PR maximum absolute value ≥300 msec; 4) PR maximum increases from baseline ≥25% if baseline >200 msec, ≥50% if baseline ≤200 msec; 5) QRS maximum absolute value ≥140 msec; 6) QRS maximum increase from baseline ≥50%.	Baseline up to Day 56
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Who Withdrew Due to Adverse Events (AEs) (SAD Period)	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. All events occurring following start of the treatment or increasing in severity were counted as treatment emergent. Events that occurred in a non-treatment period (eg, washout or follow-up) were counted as treatment emergent and attributed to the previous treatment taken. For each event, the investigator pursued and obtained adequate information both to determine the outcome and to assess whether it meets the criteria for classification as an SAE. PBO SAD cohorts = [PBO SAD (3mg, 10mg)] cohorts + [PBO SAD -> PBO QD MAD] cohorts.	Baseline up to Day 8
Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (MAD Period)	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. All events occurring following start of the treatment or increasing in severity were counted as treatment emergent. Events that occurred in a non-treatment period (eg, washout or follow-up) were counted as treatment emergent and attributed to the previous treatment taken. For each event, the investigator pursued and obtained adequate information both to determine the outcome and to assess whether it meets the criteria for classification as an SAE.	Baseline up to Day 28
Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (Psoriasis Cohorts)	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. All events occurring following start of the treatment or increasing in severity were counted as treatment emergent. Events that occurred in a non-treatment period (eg, washout or follow-up) were counted as treatment emergent and attributed to the previous treatment taken. For each event, the investigator pursued and obtained adequate information both to determine the outcome and to assess whether it meets the criteria for classification as an SAE.	Baseline up to Day 84
Number of Participants With Laboratory Abnormalities (SAD Period)	Laboratory data were listed and summarized by treatment in accordance with the sponsor reporting standards. Parameters for laboratory abnormalities evaluation included: erythrocyte mean corpuscular volume (Ery. MCV), erythrocyte mean corpuscular hemoglobin (Ery. MCH), reticulocytes/erythrocytes (%), limphocytes, eosinophils, bilirubin, aspartate aminotransferase (AST), urate, high-density lipoproteins (HDL) cholesterol, low-density lipoproteins (LDL) cholesterol, triglycerides, cholesterol, ketones, nitrite, leukocyte esterase, epithelial cells, urinalysis-bacteria. Number of participants in PBO SAD cohorts = number of participants in [PBO SAD (3mg, 10mg)] cohorts + number of participants in [PBO SAD -> PBO QD MAD] cohorts.	Baseline up to Day 8
Number of Participants With Laboratory Abnormalities (MAD Period)	Laboratory data were listed and summarized by treatment in accordance with the sponsor reporting standards. Parameters and corresponding primary criteria for laboratory abnormalities evaluation included: Ery. MCV <0.9 × LLN, Ery. Mean corpuscular hemoglobin (Ery. MCH) <0.9 × LLN or >1.1 ULN, reticulocytes/erythrocytes (%) >1.5 × ULN, lymphocytes <0.8 × LLN or >1.2 × ULN, neutrophils <0.8 × LLN, eosinophils >1.2 × ULN, bilirubin >1.5 × ULN, urate >1.2 × ULN, HDL cholesterol <0.8 × LLN, LDL cholesterol >1.2 × ULN, triglycerides >1.3 × ULN, bicarbonate >1.1 × ULN, cholesterol >1.3 × ULN, urine glucose ≥1, urine hemoglobin ≥1, nitrite ≥1, leukocyte esterase ≥1, epithelial cells ≥6/LPF, urinalysis-casts >1/LPF, urinalysis-bacteria >20/HPF, urine 24 hours creatinine >1.1 × ULN.	Baseline up to Day 28
Number of Participants With Laboratory Abnormalities (Psoriasis Cohorts)	Laboratory data were listed and summarized by treatment in accordance with the sponsor reporting standards. Parameters and corresponding primary criteria for laboratory abnormalities evaluation included: reticulocytes/erythrocytes (%) >1.5 × ULN, lymphocytes <0.8 × LLN, neutrophils <0.8 × LLN or >1.2 × ULN, eosinophils >1.2 × ULN, bilirubin >1.5 × ULN, alanine aminotransferase (ALT) >3.0 × ULN, creatinine >1.3 × ULN, urate >1.2 × ULN, HDL cholesterol <0.8 × LLN, LDL cholesterol >1.2 × ULN, triglycerides >1.3 × ULN, potassium >1.1 × ULN, bicarbonate >1.1 × ULN, glucose <0.6 × LLN or >1.5 × ULN, Creatine Kinase (CK) >2.0 × ULN, cholesterol >1.3 × ULN, urine glucose ≥1, ketones ≥1, urine hemoglobin ≥1, urine bilirubin ≥1, leukocyte esterase ≥1, epithelial cells ≥6/LPF, urinalysis-bacteria/HPF.	Baseline up to Day 56
Change in 24 Hour Creatinine Clearance From Day -1 on Day 10 (MAD Period)	Change in 24-hour creatinine clearance at Day 10 from Day -1 (baseline) during the MAD was presented by treatment group.	Day -1 and Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) (SAD Period)	AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Secondary: Dose Normalized AUCinf (AUCinf[dn]) (SAD Period)	AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). AUCinf(dn) = AUCinf / dose. Dose normalized AUC values of PF-06826647 was plotted against dose and included individual participant values and the geometric means for each dose. These plots were used to help understand the relationship between the plasma PK parameters and dose.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Area Under the Concentration-Time Profile From Time 0 to 24 Hours (AUC24) (SAD Period)	AUC24 was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) (SAD Period)	AUClast was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Dose Normalized AUClast (AUClast[dn]) (SAD Period)	AUClast(dn) = AUClast / dose. Dose normalized AUC values of PF-06826647 were plotted against dose and included individual participant values and the geometric means for each dose. These plots was used to help understand the relationship between the plasma PK parameters and dose.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Maximum Plasma Concentration (Cmax) (SAD Period)	Cmax was summarized by dosing regimen and period. It was observed directly from data.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Dose Normalized Cmax (Cmax[dn]) (SAD Period)	Cmax(dn) = Cmax / dose. To assess the relationship between Cmax and dose, dose normalized Cmax was plotted against dose, and included individual participant values and the geometric means for each dose.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Time for Cmax (Tmax) (SAD Period)	Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Terminal Elimination Half-Life ((t½) (SAD Period)	t1/2 was summarized by dosing regimen and period. It was determined by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Mean Residence Time (MRT) (SAD Period)	MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Apparent Volume of Distribution (Vz/F) (SAD Period)	Vz/F 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.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Apparent Clearance (CL/F) (SAD Period)	CL/F 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. 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.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Area Under the Plasma Concentration-Time Profile Over the Dosing Interval τ (AUCτ) (MAD Period Day 1)	AUCτ was summarized by dosing regimen and period. Dosing interval was the interval τ between administration of doses of drug. In this study, the dosing interval was 24 hours for QD dosing and 12 hours for BID dosing. It was determined by linear/log trapezoidal method.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Dose Normalized AUCτ (AUCτ[dn]) (MAD Period Day 1)	Area Under the Plasma Concentration-Time Profile over the Dosing interval τ (AUCτ). Dosing interval was the interval τ between administration of doses of drug. In this study, the dosing interval τ was 24 hours for QD dosing and 12 hours for BID dosing. AUCτ(dn) = AUCτ / Dose. To assess the relationship between the PK parameters and the dose, dose normalized AUCτ was plotted against dose, and included individual participant values and the geometric means for each dose.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Cmax (MAD Period Day 1)	Cmax was summarized by dosing regimen and period. It was observed directly from data.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Cmax(dn) (MAD Period Day 1)	Cmax(dn) = Cmax / dose. To assess the relationship between Cmax and dose, dose normalized Cmax was plotted against dose, and included individual participant values and the geometric means for each dose.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Tmax (MAD Period Day 1)	Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.	Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
AUCτ (MAD Period Day 10)	AUCτ was summarized by dosing regimen and period. Dosing interval was the interval τ between administration of doses of drug. In this study, the dosing interval was 24 hours for QD dosing and 12 hours for BID dosing. It was determined by linear/log trapezoidal method.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
AUCτ(dn) (MAD Period Day 10)	Area Under the Plasma Concentration-Time Profile over the Dosing interval τ (AUCτ). Dosing interval was the interval τ between administration of doses of drug. In this study, the dosing interval τ was 24 hours for QD dosing and 12 hours for BID dosing. AUCτ(dn) = AUCτ / Dose. To assess the relationship between the PK parameters and the dose, dose normalized AUCτ was plotted against dose, and included individual participant values and the geometric means for each dose.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Cmax (MAD Period Day 10)	Cmax was summarized by dosing regimen and period. It was observed directly from data.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Cmax(dn) (MAD Period Day 10)	Cmax(dn) = Cmax / dose. To assess the relationship between Cmax and dose, dose normalized Cmax was plotted against dose, and included individual participant values and the geometric means for each dose.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Tmax (MAD Period Day 10)	Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Average Concentration at Steady State (Cav) (MAD Period Day 10)	Cav = AUCτ,ss / τ, where ss means 'at steady state', and where the dosing interval τ was 24 hours for QD dosing and 12 hours for BID dosing. Cav was summarized by dosing regimen and period.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Lowest Concentration Observed During the Dosing Interval τ (Cmin) (MAD Period Day 10)	Cmin was observed directly from data. It was summarized by dosing regimen and period. Dosing interval was the interval τ between administration of doses of drug. In this study, the dosing interval τ was 24 hours for QD dosing and 12 hours for BID dosing.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Terminal Elimination Half-Life ((t½) (MAD Period Day 10)	t1/2 was summarized by dosing regimen and period. It was determined by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24,48,72,96,168 hours post-dose
MRT (MAD Period Day 10)	MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24,48,72,96,168 hours post-dose
Peak Trough Ratio (PTR) (MAD Period Day 10)	PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It was summarized by dosing regimen and period.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Observed Accumulation Ratio Based on AUC (Rac) (MAD Period Day 10)	Rac = AUCτ,ss / AUCτ,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac = AUCτ(Day 10) / AUCτ(Day 1). Rac was summarized by dosing regimen and period.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Observed Accumulation Ratio Based on Cmax (Rac,Cmax) (MAD Period Day 10)	Rac,Cmax = Cmax,ss / Cmax,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac,Cmax = Cmax(Day10) / Cmax(Day 1). Rac,Cmax was summarized by dosing regimen and period.	Days 1 and 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Vz/F (MAD Period Day 10)	Vz/F 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.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
CL/F (MAD Period Day 10)	CL/F 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. 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.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Cumulative Amount of Drug Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ) (MAD Period Day 10)	Dosing interval was the interval τ between administration of doses of drug. In this study, the dosing interval τ was 24 hours for QD dosing and 12 hours for BID dosing. Aeτ = Sum of [urine concentration * sample volume] for each collection interval. Aer was summarized by dosing regimen and period.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Percentage of Dose Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ%) (MAD Period Day 10)	Dosing interval was the interval τ between administration of doses of drug. In this study, the dosing interval τ was 24 hours for QD dosing and 12 hours for BID dosing. Aeτ% = Aeτ / Dose * 100. Aeτ%was summarized by dosing regimen and period.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Renal Clearance (Clr) (MAD Period Day 10)	Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Aeτ) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCτ), where dosing interval is 24 hours for QD dosing and 12 hours for BID dosing.	Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
AUCτ (Psoriasis Cohorts)	AUCτ was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
AUCτ(dn) (Psoriasis Cohorts)	AUCτ(dn) = AUCτ / Dose. To assess the relationship between the PK parameters and the dose, dose normalized AUCτ was plotted against dose, and included individual participant values and the geometric means for each dose.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Cmax (Psoriasis Cohorts)	Cmax was summarized by dosing regimen and period. It was observed directly from data.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Cmax(dn) (Psoriasis Cohorts)	Cmax was summarized by dosing regimen and period. It was observed directly from data.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Tmax (Psoriasis Cohorts)	Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Cav (Psoriasis Cohorts)	Cav = AUCτ,ss / τ, where ss means 'at steady state'. Cav was summarized by dosing regimen and period.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Cmin (Psoriasis Cohorts)	Cmin was observed directly from data. It was summarized by dosing regimen and period.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Terminal Elimination Half-Life ((t½) (Psoriasis Cohorts)	t1/2 was summarized by dosing regimen and period. It was determined by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24,168 hours post-dose
MRT (Psoriasis Cohorts)	MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24,168 hours post-dose
PTR (Psoriasis Cohorts)	PTR = Cmax,ss / Cmin,ss, it was summarized by dosing regimen and period.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Vz/F (Psoriasis Cohorts)	Vz/F 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.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
CL/F (Psoriasis Cohorts)	CL/F 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. 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.	Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 28	Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0= 0% to 6= 90-100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section*area score*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4); total possible score range: 0= no disease to 72= maximal disease.	Baseline and Day 28

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): July 14, 2017
• Primary Completion (ACTUAL): January 25, 2019
• Study Completion (ACTUAL): January 25, 2019

Study Registration Dates

• First Submitted: July 3, 2017
• First Submitted That Met QC Criteria: July 5, 2017
• First Posted (ACTUAL): July 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2020
• Last Update Submitted That Met QC Criteria: March 28, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: C2501001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No