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

Primary Purpose

Plaque Psoriasis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-06826647 tablet
PF-06826647 oral suspension
Placebo oral solution/suspension
Placebo tablet
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Plaque Psoriasis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Anaheim Clinical Trials, LLC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

PF-06826647 tablet

Placebo tablet

PF-06826647 oral suspension

Placebo oral solution/suspension

Arm Description

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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%.
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%.
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.
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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

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).
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.
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.
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.
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.
Maximum Plasma Concentration (Cmax) (SAD Period)
Cmax was summarized by dosing regimen and period. It was observed directly from data.
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.
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.
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.
Mean Residence Time (MRT) (SAD Period)
MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.
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.
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.
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.
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.
Cmax (MAD Period Day 1)
Cmax was summarized by dosing regimen and period. It was observed directly from data.
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.
Tmax (MAD Period Day 1)
Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.
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.
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.
Cmax (MAD Period Day 10)
Cmax was summarized by dosing regimen and period. It was observed directly from data.
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.
Tmax (MAD Period Day 10)
Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.
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.
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.
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.
MRT (MAD Period Day 10)
MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.
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.
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.
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.
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.
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.
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.
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.
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.
AUCτ (Psoriasis Cohorts)
AUCτ was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.
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.
Cmax (Psoriasis Cohorts)
Cmax was summarized by dosing regimen and period. It was observed directly from data.
Cmax(dn) (Psoriasis Cohorts)
Cmax was summarized by dosing regimen and period. It was observed directly from data.
Tmax (Psoriasis Cohorts)
Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.
Cav (Psoriasis Cohorts)
Cav = AUCτ,ss / τ, where ss means 'at steady state'. Cav was summarized by dosing regimen and period.
Cmin (Psoriasis Cohorts)
Cmin was observed directly from data. It was summarized by dosing regimen and period.
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.
MRT (Psoriasis Cohorts)
MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.
PTR (Psoriasis Cohorts)
PTR = Cmax,ss / Cmin,ss, it was summarized by dosing regimen and period.
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.
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.
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.

Full Information

First Posted
July 3, 2017
Last Updated
March 28, 2020
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT03210961
Brief Title
A First in Human Study to Evaluate Safety, Tolerability, and Pharmacology of PF-06826647 in Healthy Subjects and Subjects With Plaque Psoriasis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
July 14, 2017 (Actual)
Primary Completion Date
January 25, 2019 (Actual)
Study Completion Date
January 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plaque Psoriasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Combination single and multiple ascending dose design. Cohorts of participants are assigned to receive interventions based on acceptable safety, tolerability, and pharmacokinetics of previous dose cohort
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blind treatment
Allocation
Randomized
Enrollment
109 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PF-06826647 tablet
Arm Type
Experimental
Arm Title
Placebo tablet
Arm Type
Placebo Comparator
Arm Title
PF-06826647 oral suspension
Arm Type
Experimental
Arm Title
Placebo oral solution/suspension
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
PF-06826647 tablet
Intervention Description
PF-06826647 tablet for oral administration
Intervention Type
Drug
Intervention Name(s)
PF-06826647 oral suspension
Intervention Description
PF-06826647 suspension for oral administration (oral suspension to be administered to the 3mg starting dose cohort only)
Intervention Type
Other
Intervention Name(s)
Placebo oral solution/suspension
Intervention Description
placebo oral solution for the single ascending dose, first cohort only
Intervention Type
Other
Intervention Name(s)
Placebo tablet
Intervention Description
Matching placebo tablet
Primary Outcome Measure Information:
Title
Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Single Ascending Dose [SAD] Period)
Description
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.
Time Frame
Baseline up to Day 8
Title
Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Multiple Ascending Dose [MAD] Period)
Description
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.
Time Frame
Baseline up to Day 28
Title
Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)
Description
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.
Time Frame
Baseline up to Day 56
Title
Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (SAD Period)
Description
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.
Time Frame
Baseline up to Day 8
Title
Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (MAD Period)
Description
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.
Time Frame
Baseline up to Day 28
Title
Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)
Description
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.
Time Frame
Baseline up to Day 56
Title
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria (SAD Period)
Description
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.
Time Frame
Baseline up to Day 8
Title
Number of Participants With ECG Data Meeting Pre-Specified Criteria (MAD Period)
Description
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%.
Time Frame
Baseline up to Day 28
Title
Number of Participants With ECG Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)
Description
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%.
Time Frame
Baseline up to Day 56
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Who Withdrew Due to Adverse Events (AEs) (SAD Period)
Description
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.
Time Frame
Baseline up to Day 8
Title
Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (MAD Period)
Description
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.
Time Frame
Baseline up to Day 28
Title
Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (Psoriasis Cohorts)
Description
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.
Time Frame
Baseline up to Day 84
Title
Number of Participants With Laboratory Abnormalities (SAD Period)
Description
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.
Time Frame
Baseline up to Day 8
Title
Number of Participants With Laboratory Abnormalities (MAD Period)
Description
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.
Time Frame
Baseline up to Day 28
Title
Number of Participants With Laboratory Abnormalities (Psoriasis Cohorts)
Description
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.
Time Frame
Baseline up to Day 56
Title
Change in 24 Hour Creatinine Clearance From Day -1 on Day 10 (MAD Period)
Description
Change in 24-hour creatinine clearance at Day 10 from Day -1 (baseline) during the MAD was presented by treatment group.
Time Frame
Day -1 and Day 10
Secondary Outcome Measure Information:
Title
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) (SAD Period)
Description
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).
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Secondary: Dose Normalized AUCinf (AUCinf[dn]) (SAD Period)
Description
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.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Area Under the Concentration-Time Profile From Time 0 to 24 Hours (AUC24) (SAD Period)
Description
AUC24 was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) (SAD Period)
Description
AUClast was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Dose Normalized AUClast (AUClast[dn]) (SAD Period)
Description
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.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Maximum Plasma Concentration (Cmax) (SAD Period)
Description
Cmax was summarized by dosing regimen and period. It was observed directly from data.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Dose Normalized Cmax (Cmax[dn]) (SAD Period)
Description
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.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Time for Cmax (Tmax) (SAD Period)
Description
Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Terminal Elimination Half-Life ((t½) (SAD Period)
Description
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.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Mean Residence Time (MRT) (SAD Period)
Description
MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Apparent Volume of Distribution (Vz/F) (SAD Period)
Description
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.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Apparent Clearance (CL/F) (SAD Period)
Description
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.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose
Title
Area Under the Plasma Concentration-Time Profile Over the Dosing Interval τ (AUCτ) (MAD Period Day 1)
Description
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.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Dose Normalized AUCτ (AUCτ[dn]) (MAD Period Day 1)
Description
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.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Cmax (MAD Period Day 1)
Description
Cmax was summarized by dosing regimen and period. It was observed directly from data.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Cmax(dn) (MAD Period Day 1)
Description
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.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Tmax (MAD Period Day 1)
Description
Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.
Time Frame
Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
AUCτ (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
AUCτ(dn) (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Cmax (MAD Period Day 10)
Description
Cmax was summarized by dosing regimen and period. It was observed directly from data.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Cmax(dn) (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Tmax (MAD Period Day 10)
Description
Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Average Concentration at Steady State (Cav) (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Lowest Concentration Observed During the Dosing Interval τ (Cmin) (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Terminal Elimination Half-Life ((t½) (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24,48,72,96,168 hours post-dose
Title
MRT (MAD Period Day 10)
Description
MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24,48,72,96,168 hours post-dose
Title
Peak Trough Ratio (PTR) (MAD Period Day 10)
Description
PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It was summarized by dosing regimen and period.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Observed Accumulation Ratio Based on AUC (Rac) (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Observed Accumulation Ratio Based on Cmax (Rac,Cmax) (MAD Period Day 10)
Description
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.
Time Frame
Days 1 and 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Vz/F (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
CL/F (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Cumulative Amount of Drug Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ) (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Percentage of Dose Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ%) (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
Renal Clearance (Clr) (MAD Period Day 10)
Description
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.
Time Frame
Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose
Title
AUCτ (Psoriasis Cohorts)
Description
AUCτ was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
AUCτ(dn) (Psoriasis Cohorts)
Description
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.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
Cmax (Psoriasis Cohorts)
Description
Cmax was summarized by dosing regimen and period. It was observed directly from data.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
Cmax(dn) (Psoriasis Cohorts)
Description
Cmax was summarized by dosing regimen and period. It was observed directly from data.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
Tmax (Psoriasis Cohorts)
Description
Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
Cav (Psoriasis Cohorts)
Description
Cav = AUCτ,ss / τ, where ss means 'at steady state'. Cav was summarized by dosing regimen and period.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
Cmin (Psoriasis Cohorts)
Description
Cmin was observed directly from data. It was summarized by dosing regimen and period.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
Terminal Elimination Half-Life ((t½) (Psoriasis Cohorts)
Description
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.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24,168 hours post-dose
Title
MRT (Psoriasis Cohorts)
Description
MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24,168 hours post-dose
Title
PTR (Psoriasis Cohorts)
Description
PTR = Cmax,ss / Cmin,ss, it was summarized by dosing regimen and period.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
Vz/F (Psoriasis Cohorts)
Description
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.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
CL/F (Psoriasis Cohorts)
Description
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.
Time Frame
Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose
Title
Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 28
Description
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.
Time Frame
Baseline and Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Anaheim Clinical Trials, LLC
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C2501001
Description
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Learn more about this trial

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

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