Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03210961
Recruitment Status : Completed
First Posted : July 7, 2017
Results First Posted : March 31, 2020
Last Update Posted : March 31, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Plaque Psoriasis Drug: PF-06826647 tablet Drug: PF-06826647 oral suspension Other: Placebo oral solution/suspension Other: Placebo tablet Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind treatment
Primary Purpose: Treatment
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
Actual Study Start Date : July 14, 2017
Actual Primary Completion Date : January 25, 2019
Actual Study Completion Date : January 25, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

Arm Intervention/treatment
Experimental: PF-06826647 tablet Drug: PF-06826647 tablet
PF-06826647 tablet for oral administration

Placebo Comparator: Placebo tablet Other: Placebo tablet
Matching placebo tablet

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




Primary Outcome Measures :
  1. Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Single Ascending Dose [SAD] Period) [ Time Frame: Baseline up to Day 8 ]

    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.


  2. Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Multiple Ascending Dose [MAD] Period) [ Time Frame: Baseline up to Day 28 ]
    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.

  3. Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Psoriasis Cohorts) [ Time Frame: Baseline up to Day 56 ]
    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.

  4. Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (SAD Period) [ Time Frame: Baseline up to Day 8 ]

    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.


  5. Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (MAD Period) [ Time Frame: Baseline up to Day 28 ]
    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.

  6. Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (Psoriasis Cohorts) [ Time Frame: Baseline up to Day 56 ]
    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.

  7. Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria (SAD Period) [ Time Frame: Baseline up to Day 8 ]

    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.


  8. Number of Participants With ECG Data Meeting Pre-Specified Criteria (MAD Period) [ Time Frame: Baseline up to Day 28 ]
    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%.

  9. Number of Participants With ECG Data Meeting Pre-Specified Criteria (Psoriasis Cohorts) [ Time Frame: Baseline up to Day 56 ]
    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%.

  10. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Who Withdrew Due to Adverse Events (AEs) (SAD Period) [ Time Frame: Baseline up to Day 8 ]

    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.


  11. Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (MAD Period) [ Time Frame: Baseline up to Day 28 ]
    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.

  12. Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (Psoriasis Cohorts) [ Time Frame: Baseline up to Day 84 ]
    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.

  13. Number of Participants With Laboratory Abnormalities (SAD Period) [ Time Frame: Baseline up to Day 8 ]

    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.


  14. Number of Participants With Laboratory Abnormalities (MAD Period) [ Time Frame: Baseline up to Day 28 ]
    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.

  15. Number of Participants With Laboratory Abnormalities (Psoriasis Cohorts) [ Time Frame: Baseline up to Day 56 ]
    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.

  16. Change in 24 Hour Creatinine Clearance From Day -1 on Day 10 (MAD Period) [ Time Frame: Day -1 and Day 10 ]
    Change in 24-hour creatinine clearance at Day 10 from Day -1 (baseline) during the MAD was presented by treatment group.


Secondary Outcome Measures :
  1. Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    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).

  2. Secondary: Dose Normalized AUCinf (AUCinf[dn]) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    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.

  3. Area Under the Concentration-Time Profile From Time 0 to 24 Hours (AUC24) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    AUC24 was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.

  4. Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    AUClast was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.

  5. Dose Normalized AUClast (AUClast[dn]) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    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.

  6. Maximum Plasma Concentration (Cmax) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    Cmax was summarized by dosing regimen and period. It was observed directly from data.

  7. Dose Normalized Cmax (Cmax[dn]) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    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.

  8. Time for Cmax (Tmax) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.

  9. Terminal Elimination Half-Life ((t½) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    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.

  10. Mean Residence Time (MRT) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.

  11. Apparent Volume of Distribution (Vz/F) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    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.

  12. Apparent Clearance (CL/F) (SAD Period) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose ]
    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.

  13. Area Under the Plasma Concentration-Time Profile Over the Dosing Interval τ (AUCτ) (MAD Period Day 1) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  14. Dose Normalized AUCτ (AUCτ[dn]) (MAD Period Day 1) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]

    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.


  15. Cmax (MAD Period Day 1) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    Cmax was summarized by dosing regimen and period. It was observed directly from data.

  16. Cmax(dn) (MAD Period Day 1) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  17. Tmax (MAD Period Day 1) [ Time Frame: Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.

  18. AUCτ (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  19. AUCτ(dn) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]

    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.


  20. Cmax (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    Cmax was summarized by dosing regimen and period. It was observed directly from data.

  21. Cmax(dn) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  22. Tmax (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.

  23. Average Concentration at Steady State (Cav) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  24. Lowest Concentration Observed During the Dosing Interval τ (Cmin) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  25. Terminal Elimination Half-Life ((t½) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24,48,72,96,168 hours post-dose ]
    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.

  26. MRT (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24,48,72,96,168 hours post-dose ]
    MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.

  27. Peak Trough Ratio (PTR) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It was summarized by dosing regimen and period.

  28. Observed Accumulation Ratio Based on AUC (Rac) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  29. Observed Accumulation Ratio Based on Cmax (Rac,Cmax) (MAD Period Day 10) [ Time Frame: Days 1 and 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  30. Vz/F (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  31. CL/F (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  32. Cumulative Amount of Drug Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  33. Percentage of Dose Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ%) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  34. Renal Clearance (Clr) (MAD Period Day 10) [ Time Frame: Day 10 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose ]
    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.

  35. AUCτ (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    AUCτ was summarized by dosing regimen and period. It was determined by linear/log trapezoidal method.

  36. AUCτ(dn) (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    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.

  37. Cmax (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    Cmax was summarized by dosing regimen and period. It was observed directly from data.

  38. Cmax(dn) (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    Cmax was summarized by dosing regimen and period. It was observed directly from data.

  39. Tmax (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    Tmax was summarized by dosing regimen and period. It was observed directly from data as time of first occurrence.

  40. Cav (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    Cav = AUCτ,ss / τ, where ss means 'at steady state'. Cav was summarized by dosing regimen and period.

  41. Cmin (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    Cmin was observed directly from data. It was summarized by dosing regimen and period.

  42. Terminal Elimination Half-Life ((t½) (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24,168 hours post-dose ]
    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.

  43. MRT (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24,168 hours post-dose ]
    MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from time 0 to infinity.

  44. PTR (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    PTR = Cmax,ss / Cmin,ss, it was summarized by dosing regimen and period.

  45. Vz/F (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    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.

  46. CL/F (Psoriasis Cohorts) [ Time Frame: Day 28 pre-dose, and 0.5,1,2,4,6,8,12,16,24 hours post-dose ]
    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.

  47. Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 28 [ Time Frame: Baseline and 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03210961


Locations
Layout table for location information
United States, California
Anaheim Clinical Trials, LLC
Anaheim, California, United States, 92801
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] April 5, 2018
Statistical Analysis Plan  [PDF] June 12, 2018

Additional Information:
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03210961    
Other Study ID Numbers: C2501001
First Posted: July 7, 2017    Key Record Dates
Results First Posted: March 31, 2020
Last Update Posted: March 31, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases