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

NCT03210961 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C2501001
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

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.

Conditions

Plaque Psoriasis

Outcome Measures

Primary Outcomes (16)

• Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Single Ascending Dose [SAD] Period)

  Maximum absolute values and changes from baseline for vital signs (for supine systolic/diastolic blood pressure \[BP\] and supine pulse rate \[PR\]) were summarized descriptively by treatment. Numbers of participants meeting the categorical criteria were provided. Number of participants in PBO SAD cohorts = number of participants in \[PBO SAD (3mg, 10mg)\] cohorts + number of participants in \[PBO SAD -\> PBO QD MAD\] cohorts.

  Baseline up to Day 8

• Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Multiple Ascending Dose [MAD] Period)

  Maximum absolute values and changes from baseline for vital signs (for supine systolic/diastolic blood pressure and supine pulse rate) were summarized descriptively by treatment. Numbers of participants meeting the categorical criteria were provided.

  Baseline up to Day 28

• Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)

  Maximum absolute values and changes from baseline for vital signs (for supine systolic/diastolic blood pressure and supine pulse rate) were summarized descriptively by treatment. Numbers of participants meeting the categorical criteria were provided.

  Baseline up to Day 56

• Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (SAD Period)

  Physical examinations were conducted by a physician, trained physician assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision. Number of participants in PBO SAD cohorts = number of participants in \[PBO SAD (3mg, 10mg)\] cohorts + number of participants in \[PBO SAD -\> PBO QD MAD\] cohorts.

  Baseline up to Day 8

• Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (MAD Period)

  Physical examinations were conducted by a physician, trained physician assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.

  Baseline up to Day 28

• Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)

  Physical examinations were conducted by a physician, trained physician assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.

  Baseline up to Day 56

• Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria (SAD Period)

  ECG endpoints and changes from baseline (QTcF, PR and QRS) were summarized descriptively by cohort and treatment using pre-defined categories. Numbers of participants meeting the categorical criteria were provided. All planned and unplanned post-dose time points were counted in these categorical summaries. Categorical summarization criteria for ECG were as follows: 1) QTcF maximum absolute value ≥450 and \<480 millisecond (msec), ≥480 and \<500 msec. ≥500 msec; 2) QTcF maximum increase ≥30 and \<60 msec, ≥60 msec; 3) PR maximum absolute value ≥300 msec; 4) PR maximum increases from baseline ≥25% if baseline \>200 msec, ≥50% if baseline ≤200 msec; 5) QRS maximum absolute value ≥140 msec; 6) QRS maximum increase from baseline ≥50%. Number of participants in PBO SAD cohorts = number of participants in \[PBO SAD (3mg, 10mg)\] cohorts + number of participants in \[PBO SAD -\> PBO QD MAD\] cohorts.

  Baseline up to Day 8

• Number of Participants With ECG Data Meeting Pre-Specified Criteria (MAD Period)

  ECG endpoints and changes from baseline (QTcF, PR and QRS) were summarized descriptively by cohort and treatment using pre-defined categories. Numbers of participants meeting the categorical criteria were provided. All planned and unplanned post-dose time points were counted in these categorical summaries. Categorical summarization criteria for ECG were as follows: 1) QTcF maximum absolute value ≥450 and \<480 millisecond (msec), ≥480 and \<500 msec. ≥500 msec; 2) QTcF maximum increase ≥30 and \<60 msec, ≥60 msec; 3) PR maximum absolute value ≥300 msec; 4) PR maximum increases from baseline ≥25% if baseline \>200 msec, ≥50% if baseline ≤200 msec; 5) QRS maximum absolute value ≥140 msec; 6) QRS maximum increase from baseline ≥50%.

  Baseline up to Day 28

• Number of Participants With ECG Data Meeting Pre-Specified Criteria (Psoriasis Cohorts)

  ECG endpoints and changes from baseline (QTcF, PR and QRS) were summarized descriptively by cohort and treatment using pre-defined categories. Numbers of participants meeting the categorical criteria were provided. All planned and unplanned post-dose time points were counted in these categorical summaries. Categorical summarization criteria for ECG were as follows: 1) QTcF maximum absolute value ≥450 and \<480 millisecond (msec), ≥480 and \<500 msec. ≥500 msec; 2) QTcF maximum increase ≥30 and \<60 msec, ≥60 msec; 3) PR maximum absolute value ≥300 msec; 4) PR maximum increases from baseline ≥25% if baseline \>200 msec, ≥50% if baseline ≤200 msec; 5) QRS maximum absolute value ≥140 msec; 6) QRS maximum increase from baseline ≥50%.

  Baseline up to Day 56

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Who Withdrew Due to Adverse Events (AEs) (SAD Period)

  An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. All events occurring following start of the treatment or increasing in severity were counted as treatment emergent. Events that occurred in a non-treatment period (eg, washout or follow-up) were counted as treatment emergent and attributed to the previous treatment taken. For each event, the investigator pursued and obtained adequate information both to determine the outcome and to assess whether it meets the criteria for classification as an SAE. PBO SAD cohorts = \[PBO SAD (3mg, 10mg)\] cohorts + \[PBO SAD -\> PBO QD MAD\] cohorts.

  Baseline up to Day 8

• Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (MAD Period)

  An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. All events occurring following start of the treatment or increasing in severity were counted as treatment emergent. Events that occurred in a non-treatment period (eg, washout or follow-up) were counted as treatment emergent and attributed to the previous treatment taken. For each event, the investigator pursued and obtained adequate information both to determine the outcome and to assess whether it meets the criteria for classification as an SAE.

  Baseline up to Day 28

• Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (Psoriasis Cohorts)

  An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. All events occurring following start of the treatment or increasing in severity were counted as treatment emergent. Events that occurred in a non-treatment period (eg, washout or follow-up) were counted as treatment emergent and attributed to the previous treatment taken. For each event, the investigator pursued and obtained adequate information both to determine the outcome and to assess whether it meets the criteria for classification as an SAE.

  Baseline up to Day 84

• Number of Participants With Laboratory Abnormalities (SAD Period)

  Laboratory data were listed and summarized by treatment in accordance with the sponsor reporting standards. Parameters for laboratory abnormalities evaluation included: erythrocyte mean corpuscular volume (Ery. MCV), erythrocyte mean corpuscular hemoglobin (Ery. MCH), reticulocytes/erythrocytes (%), limphocytes, eosinophils, bilirubin, aspartate aminotransferase (AST), urate, high-density lipoproteins (HDL) cholesterol, low-density lipoproteins (LDL) cholesterol, triglycerides, cholesterol, ketones, nitrite, leukocyte esterase, epithelial cells, urinalysis-bacteria. Number of participants in PBO SAD cohorts = number of participants in \[PBO SAD (3mg, 10mg)\] cohorts + number of participants in \[PBO SAD -\> PBO QD MAD\] cohorts.

  Baseline up to Day 8

• Number of Participants With Laboratory Abnormalities (MAD Period)

  Laboratory data were listed and summarized by treatment in accordance with the sponsor reporting standards. Parameters and corresponding primary criteria for laboratory abnormalities evaluation included: Ery. MCV \<0.9 × LLN, Ery. Mean corpuscular hemoglobin (Ery. MCH) \<0.9 × LLN or \>1.1 ULN, reticulocytes/erythrocytes (%) \>1.5 × ULN, lymphocytes \<0.8 × LLN or \>1.2 × ULN, neutrophils \<0.8 × LLN, eosinophils \>1.2 × ULN, bilirubin \>1.5 × ULN, urate \>1.2 × ULN, HDL cholesterol \<0.8 × LLN, LDL cholesterol \>1.2 × ULN, triglycerides \>1.3 × ULN, bicarbonate \>1.1 × ULN, cholesterol \>1.3 × ULN, urine glucose ≥1, urine hemoglobin ≥1, nitrite ≥1, leukocyte esterase ≥1, epithelial cells ≥6/LPF, urinalysis-casts \>1/LPF, urinalysis-bacteria \>20/HPF, urine 24 hours creatinine \>1.1 × ULN.

  Baseline up to Day 28

• Number of Participants With Laboratory Abnormalities (Psoriasis Cohorts)

  Laboratory data were listed and summarized by treatment in accordance with the sponsor reporting standards. Parameters and corresponding primary criteria for laboratory abnormalities evaluation included: reticulocytes/erythrocytes (%) \>1.5 × ULN, lymphocytes \<0.8 × LLN, neutrophils \<0.8 × LLN or \>1.2 × ULN, eosinophils \>1.2 × ULN, bilirubin \>1.5 × ULN, alanine aminotransferase (ALT) \>3.0 × ULN, creatinine \>1.3 × ULN, urate \>1.2 × ULN, HDL cholesterol \<0.8 × LLN, LDL cholesterol \>1.2 × ULN, triglycerides \>1.3 × ULN, potassium \>1.1 × ULN, bicarbonate \>1.1 × ULN, glucose \<0.6 × LLN or \>1.5 × ULN, Creatine Kinase (CK) \>2.0 × ULN, cholesterol \>1.3 × ULN, urine glucose ≥1, ketones ≥1, urine hemoglobin ≥1, urine bilirubin ≥1, leukocyte esterase ≥1, epithelial cells ≥6/LPF, urinalysis-bacteria/HPF.

  Baseline up to Day 56

• Change in 24 Hour Creatinine Clearance From Day -1 on Day 10 (MAD Period)

  Change in 24-hour creatinine clearance at Day 10 from Day -1 (baseline) during the MAD was presented by treatment group.

  Day -1 and Day 10

Secondary Outcomes (47)

• Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) (SAD Period)

  Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose

• Secondary: Dose Normalized AUCinf (AUCinf[dn]) (SAD Period)

  Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose

• Area Under the Concentration-Time Profile From Time 0 to 24 Hours (AUC24) (SAD Period)

  Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24 hours post-dose

• Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) (SAD Period)

  Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose

• Dose Normalized AUClast (AUClast[dn]) (SAD Period)

  Day 1 pre-dose, and 0.5,1,2,4,6,8,12,24,36,48,72,168 hours post-dose

Study Arms (4)

PF-06826647 tablet

EXPERIMENTAL

Drug: PF-06826647 tablet

Placebo tablet

PLACEBO COMPARATOR

Other: Placebo tablet

PF-06826647 oral suspension

EXPERIMENTAL

Drug: PF-06826647 oral suspension

Placebo oral solution/suspension

PLACEBO COMPARATOR

Other: Placebo oral solution/suspension

Interventions

PF-06826647 tablet DRUG

PF-06826647 tablet for oral administration

PF-06826647 tablet

PF-06826647 oral suspension DRUG

PF-06826647 suspension for oral administration (oral suspension to be administered to the 3mg starting dose cohort only)

PF-06826647 oral suspension

Placebo oral solution/suspension OTHER

placebo oral solution for the single ascending dose, first cohort only

Placebo oral solution/suspension

Placebo tablet OTHER

Matching placebo tablet

Placebo tablet

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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)
• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Related Publications (1)

• Tehlirian C, Peeva E, Kieras E, Scaramozza M, Roberts ES, Singh RSP, Pradhan V, Banerjee A, Garcet S, Xi L, Gale JD, Vincent MS, Krueger J. Safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of the oral TYK2 inhibitor PF-06826647 in participants with plaque psoriasis: a phase 1, randomised, double-blind, placebo-controlled, parallel-group study. Lancet Rheumatol. 2021 Mar;3(3):e204-e213. doi: 10.1016/S2665-9913(20)30397-0. Epub 2020 Dec 24.

  PMID: 38279383 DERIVED

Related Links

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

MeSH Terms

Interventions

ropsacitinib; Suspensions

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind treatment
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: July 3, 2017
• First Posted: July 7, 2017
• Study Start: July 14, 2017
• Primary Completion: January 25, 2019
• Study Completion: January 25, 2019
• Last Updated: March 31, 2020
• Results First Posted: March 31, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)