NCT03210961

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

Completed Phase 1 Results posted Last updated 31 March 2020

What this trial tests

Phase 1 trial testing PF-06826647 tablet in Plaque Psoriasis in 109 participants. Completed in 25 January 2019.

Timeline

14 July 2017

Primary endpoint
25 January 2019

25 January 2019

Quick facts

Lead sponsor	Pfizer
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	quadruple
Primary purpose	treatment
Enrollment	109
Start date	14 July 2017
Primary completion	25 January 2019
Estimated completion	25 January 2019
Sites	1 location across United States

Drugs / interventions tested

• PF-06826647 tablet
• PF-06826647 oral suspension
• Placebo oral solution/suspension
• Placebo tablet

Conditions studied

• Plaque Psoriasis — all drugs for Plaque Psoriasis →

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 55, any sex, with Plaque Psoriasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Supine diastolic BP Value <50 mmHg

Group	Value	95% CI
PBO SAD	2
PF-06826647 3 mg SAD	2
PF-06826647 10 mg SAD	1
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	1
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Supine diastolic BP Change (Chg) ≥20 mmHg increase

Group	Value	95% CI
PBO SAD	3
PF-06826647 3 mg SAD	1
PF-06826647 10 mg SAD	1
PF-06826647 30 mg SAD	2
PF-06826647 100 mg SAD	1
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	2

Supine diastolic BP Chg ≥20 mmHg decrease

Group	Value	95% CI
PBO SAD	2
PF-06826647 3 mg SAD	1
PF-06826647 10 mg SAD	2
PF-06826647 30 mg SAD	1
PF-06826647 100 mg SAD	2
PF-06826647 400 mg SAD	1
PF-06826647 1600 mg SAD	0

Supine pulse rate Value <40 beats per minute (bpm)

Group	Value	95% CI
PBO SAD	1
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Supine pulse rate Value >120 bpm

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Supine systolic BP Value <90mmHg

Group	Value	95% CI
PBO SAD	1
PF-06826647 3 mg SAD	1
PF-06826647 10 mg SAD	2
PF-06826647 30 mg SAD	1
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Supine systolic BP Chg ≥30 mmHg increase

Group	Value	95% CI
PBO SAD	2
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Supine systolic BP Chg ≥30mmHg decrease

Group	Value	95% CI
PBO SAD	2
PF-06826647 3 mg SAD	1
PF-06826647 10 mg SAD	1
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	1
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

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

Supine diastolic BP Value < 50 mmHg

Group	Value	95% CI
PBO QD MAD (JP PBO Included)	1
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	1
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	1
PF-06826647 400 mg QD MAD JP	1

Supine diastolic BP Chg ≥ 20 mmHg increase

Group	Value	95% CI
PBO QD MAD (JP PBO Included)	1
PBO BID	0
PF-06826647 30 mg QD MAD	1
PF-06826647 100 mg QD MAD	1
PF-06826647 400 mg QD MAD	1
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	3
PF-06826647 400 mg QD MAD JP	0

Supine diastolic BP Chg ≥ 20 mmHg decrease

Group	Value	95% CI
PBO QD MAD (JP PBO Included)	4
PBO BID	0
PF-06826647 30 mg QD MAD	2
PF-06826647 100 mg QD MAD	1
PF-06826647 400 mg QD MAD	1
PF-06826647 1200 mg QD MAD	1
PF-06826647 200 mg BID	1
PF-06826647 400 mg QD MAD JP	2

Supine pulse rate Value < 40 bpm

Group	Value	95% CI
PBO QD MAD (JP PBO Included)	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

Supine pulse rate Value > 120 bpm

Group	Value	95% CI
PBO QD MAD (JP PBO Included)	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

Supine systolic blood pressure Value < 90 mmHg

Group	Value	95% CI
PBO QD MAD (JP PBO Included)	1
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	1

Supine systolic BP Chg ≥ 30 mmHg increase

Group	Value	95% CI
PBO QD MAD (JP PBO Included)	1
PBO BID	0
PF-06826647 30 mg QD MAD	1
PF-06826647 100 mg QD MAD	1
PF-06826647 400 mg QD MAD	2
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

Supine systolic BP Chg ≥ 30 mmHg decrease

Group	Value	95% CI
PBO QD MAD (JP PBO Included)	0
PBO BID	0
PF-06826647 30 mg QD MAD	1
PF-06826647 100 mg QD MAD	1
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

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

Supine diastolic blood pressure Value < 50 mmHg

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	1
PF-06826647 100 mg QD PSO	1

Supine diastolic BP Chg ≥ 20 mmHg increase

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	3
PF-06826647 100 mg QD PSO	5

Supine diastolic BP Chg ≥ 20 mmHg decrease

Group	Value	95% CI
PBO QD PSO	6
PF-06826647 400 mg QD PSO	7
PF-06826647 100 mg QD PSO	4

Supine pulse rate Value < 40 bpm

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

Supine pulse rate Value > 120 bpm

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

Supine systolic BP Value < 90 mmHg

Group	Value	95% CI
PBO QD PSO	1
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

Supine systolic BP Chg ≥ 30 mmHg increase

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	1
PF-06826647 100 mg QD PSO	2

Supine systolic BP Chg ≥ 30 mmHg decrease

Group	Value	95% CI
PBO QD PSO	6
PF-06826647 400 mg QD PSO	5
PF-06826647 100 mg QD PSO	1

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

cardiovascular

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

ears

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

eyes

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

gastrointestinal

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

general appearance

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

head

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

heart

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

lungs

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

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

cardiovascular

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

ears

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

eyes

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

gastrointestinal

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

general appearance

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

head

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

heart

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

lungs

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

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

cardiovascular

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

ears at screening

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

ears at Day 28

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	1
PF-06826647 100 mg QD PSO	0

eyes

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

gastrointestinal

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

general appearance

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

head

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

heart

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria (SAD Period) Primary · 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 ≥2

PR maximum absolute value ≥300 msec

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

PR maximum increase from baseline ≥25/50%

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

QRS maximum absolute value ≥140 msec

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

QRS maximum increase from baseline ≥50%

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

QTCF maximum absolute value ≥450 and <480 msec

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	1
PF-06826647 1600 mg SAD	0

QTCF maximum absolute value ≥480 and <500 msec

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

QTCF maximum absolute value ≥500 msec

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

QTCF maximum increase ≥30 and <60 msec

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	1
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	1
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Number of Participants With ECG Data Meeting Pre-Specified Criteria (MAD Period) Primary · 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 ≥2

PR maximum absolute value ≥300 msec

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

PR maximum increase from baseline ≥25/50%

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

QRS maximum absolute value ≥140 msec

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

QRS maximum increase from baseline ≥50%

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

QTCF maximum absolute value ≥450 and <480 msec

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	1
PF-06826647 400 mg QD MAD	1
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	1

QTCF maximum absolute value ≥480 and <500 msec

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

QTCF maximum absolute value ≥500 msec

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

QTCF maximum increase ≥30 and <60 msec

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

Number of Participants With ECG Data Meeting Pre-Specified Criteria (Psoriasis Cohorts) Primary · 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 ≥2

PR maximum absolute value ≥300 msec

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

PR maximum increase from baseline ≥25/50%

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

QRS maximum absolute value ≥140 msec

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

QRS maximum increase from baseline ≥50%

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

QTCF maximum absolute value ≥450 and <480 msec

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

QTCF maximum absolute value ≥480 and <500 msec

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

QTCF maximum absolute value ≥500 msec

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

QTCF maximum increase ≥30 and <60 msec

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

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

Participants with AEs (AC)

Group	Value	95% CI
PBO SAD	1
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	1
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	2

Participants with AEs (TR)

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	1
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Participants with SAEs (AC)

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Participants with SAEs (TR)

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Participants with severe AEs (AC)

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Participants with severe AEs (TR)

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Participants withdrew due to AEs (AC)

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

Participants withdrew due to AEs (TR)

Group	Value	95% CI
PBO SAD	0
PF-06826647 3 mg SAD	0
PF-06826647 10 mg SAD	0
PF-06826647 30 mg SAD	0
PF-06826647 100 mg SAD	0
PF-06826647 400 mg SAD	0
PF-06826647 1600 mg SAD	0

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

Participants with AEs (AC)

Group	Value	95% CI
PBO QD MAD	2
PBO BID	0
PF-06826647 30 mg QD MAD	2
PF-06826647 100 mg QD MAD	1
PF-06826647 400 mg QD MAD	1
PF-06826647 1200 mg QD MAD	1
PF-06826647 200 mg BID	3
PF-06826647 400 mg QD MAD JP	1

Participants with AEs (TR)

Group	Value	95% CI
PBO QD MAD	1
PBO BID	0
PF-06826647 30 mg QD MAD	1
PF-06826647 100 mg QD MAD	1
PF-06826647 400 mg QD MAD	1
PF-06826647 1200 mg QD MAD	1
PF-06826647 200 mg BID	2
PF-06826647 400 mg QD MAD JP	1

Participants with SAEs (AC)

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

Participants with SAEs (TR)

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

Participants with severe AEs (AC)

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

Participants with severe AEs (TR)

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

Participants withdrew due to AEs (AC)

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

Participants withdrew due to AEs (TR)

Group	Value	95% CI
PBO QD MAD	0
PBO BID	0
PF-06826647 30 mg QD MAD	0
PF-06826647 100 mg QD MAD	0
PF-06826647 400 mg QD MAD	0
PF-06826647 1200 mg QD MAD	0
PF-06826647 200 mg BID	0
PF-06826647 400 mg QD MAD JP	0

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

Participants with AEs (AC)

Group	Value	95% CI
PBO QD PSO	7
PF-06826647 400 mg QD PSO	12
PF-06826647 100 mg QD PSO	5

Participants with AEs (TR)

Group	Value	95% CI
PBO QD PSO	5
PF-06826647 400 mg QD PSO	5
PF-06826647 100 mg QD PSO	3

Participants with SAEs (AC)

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

Participants with SAEs (TR)

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

Participants with severe AEs (AC)

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

Participants with severe AEs (TR)

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	0
PF-06826647 100 mg QD PSO	0

Participants withdrew due to AEs (AC)

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	1
PF-06826647 100 mg QD PSO	0

Participants withdrew due to AEs (TR)

Group	Value	95% CI
PBO QD PSO	0
PF-06826647 400 mg QD PSO	1
PF-06826647 100 mg QD PSO	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Day 8 for SAD Cohorts, which included PF-06826647 3mg, 10mg, 30mg, 100mg, 400mg, and 1600mg SD cohorts as well as placebo matching each SAD cohort. Baseline up to Day 28 for MAD Cohorts, which included PF-06826647 30mg, 100mg, 400mg, 1200mg QD, 200mg BID, 400mg QD JP, as well as placebo matching each MAD cohort. Baseline up to Day 84 for Psoriasis Cohorts, which included PF-06826647 400mg and 100mg QD cohorts, as well as placebo matching each psoriasis cohort.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo SAD

Serious: 0/13 (0%)

Deaths: 0/13

Placebo QD MAD (JP Placebo Included)

Serious: 0/9 (0%)

Deaths: 0/9

Placebo BID

Serious: 0/2 (0%)

Deaths: 0/2

PF-06826647 3 mg SAD

Serious: 0/6 (0%)

Deaths: 0/6

PF-06826647 10 mg SAD

Serious: 0/6 (0%)

Deaths: 0/6

PF-06826647 30 mg SAD

Serious: 0/8 (0%)

Deaths: 0/8

PF-06826647 30 mg QD MAD

Serious: 0/6 (0%)

Deaths: 0/6

PF-06826647 100 mg SAD

Serious: 0/7 (0%)

Deaths: 0/7

PF-06826647 100 mg QD MAD

Serious: 0/6 (0%)

Deaths: 0/6

PF-06826647 400 mg SAD

Serious: 0/8 (0%)

Deaths: 0/8

PF-06826647 400 mg QD MAD

Serious: 0/6 (0%)

Deaths: 0/6

PF-06826647 1600 mg SAD

Serious: 0/6 (0%)

Deaths: 0/6

PF-06826647 1200 mg QD MAD

Serious: 0/5 (0%)

Deaths: 0/5

PF-06826647 200 mg BID

Serious: 0/7 (0%)

Deaths: 0/7

PF-06826647 400 mg QD MAD JP

Serious: 0/5 (0%)

Deaths: 0/5

Placebo QD PSO

Serious: 0/14 (0%)

Deaths: 0/14

PF-06826647 400 mg QD PSO

Serious: 0/15 (0%)

Deaths: 0/15

PF-06826647 100 mg QD PSO

Serious: 0/11 (0%)

Deaths: 0/11

Other adverse events (38 terms — click to expand)

Reaction	System	Placebo SAD	Placebo QD MAD (JP Placebo…	Placebo BID	PF-06826647 3 mg SAD	PF-06826647 10 mg SAD	PF-06826647 30 mg SAD	PF-06826647 30 mg QD MAD	PF-06826647 100 mg SAD	PF-06826647 100 mg QD MAD	PF-06826647 400 mg SAD	PF-06826647 400 mg QD MAD	PF-06826647 1600 mg SAD	PF-06826647 1200 mg QD MAD	PF-06826647 200 mg BID	PF-06826647 400 mg QD MAD JP	Placebo QD PSO	PF-06826647 400 mg QD PSO	PF-06826647 100 mg QD PSO
Blood creatinine increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Sinus headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Cerumen impaction	Ear and labyrinth disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Ear discomfort	Ear and labyrinth disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Epigastric discomfort	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Faeces hard	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Face oedema	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Oedema	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Peripheral swelling	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Secretion discharge	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Otitis externa	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Postoperative wound infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Periorbital haematoma	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Periorbital haemorrhage	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Blood creatine phosphokinase	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Blood uric acid increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Body temperature	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dysuria	Renal and urinary disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Urticaria	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Data from ClinicalTrials.gov NCT03210961 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Emerging Topical and Systemic JAK Inhibitors in Dermatology.
   Solimani F, Meier K, Ghoreschi K. · · 2019 · cited 199× · PMID 31849996 · DOI 10.3389/fimmu.2019.02847
2. Targeting the Janus Kinase Family in Autoimmune Skin Diseases.
   Howell MD, Kuo FI, Smith PA. · · 2019 · cited 180× · PMID 31649667 · DOI 10.3389/fimmu.2019.02342
3. Mendelian randomization and clinical trial evidence supports TYK2 inhibition as a therapeutic target for autoimmune diseases.
   Yuan S, Wang L, Zhang H, Xu F, et al · · 2023 · cited 61× · PMID 36842216 · DOI 10.1016/j.ebiom.2023.104488
4. SOCS-JAK-STAT inhibitors and SOCS mimetics as treatment options for autoimmune uveitis, psoriasis, lupus, and autoimmune encephalitis.
   Pandey R, Bakay M, Hakonarson H. · · 2023 · cited 45× · PMID 38022642 · DOI 10.3389/fimmu.2023.1271102
5. Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors.
   Martin G. · · 2023 · cited 35× · PMID 36592300 · DOI 10.1007/s13555-022-00878-9
6. 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.
   Tehlirian C, Peeva E, Kieras E, Scaramozza M, et al · · 2021 · cited 29× · PMID 38279383 · DOI 10.1016/s2665-9913(20)30397-0
7. New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis.
   Carmona-Rocha E, Rusiñol L, Puig L. · · 2024 · cited 28× · PMID 38399292 · DOI 10.3390/pharmaceutics16020239
8. Safety and Pharmacokinetics of the Oral TYK2 Inhibitor PF-06826647: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study.
   Singh RSP, Pradhan V, Roberts ES, Scaramozza M, et al · · 2021 · cited 23× · PMID 33290616 · DOI 10.1111/cts.12929