Clinical trial NCT02310750: A Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06700841, With Bioavailability/Food Effect Investigation
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-06700841 In Healthy Subjects And Subjects With Plaque Psoriasis And Bioavailability Of A Tablet Formulation Relative To Suspension Formulation And The Effect Of Food On A Tablet Formulation Of Pf-06700841
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Plaque Psoriasis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-12-08
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The main purpose of the study is to determine if PF-06700841 is safe and well tolerated when administered to humans. A secondary purpose is to assess what the body does to PF-06700841 and to assess what PF-06700841 does to the body when given as single and multiple doses. The pharmacokinetic properties of different forms of PF-06700841 may be studied (tablet and solution/suspension forms).


Eligibility criteria: Inclusion Criteria:

Key Inclusion Criteria for Healthy Subject Cohorts:

* Healthy male subjects and/or female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive
* No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)

Key Inclusion Criteria for Psoriasis Subject Cohorts:

* Male subjects and/or female subjects of non-childbearing potential with a diagnosis of plaque psoriasis who are between the ages of 18 and 65 years, inclusive
* Have a diagnosis of plaque psoriasis for at least 6 months prior to first study dose

Exclusion Criteria:

Key Exclusion Criteria for Healthy Subject Cohorts:

* 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)
* Males of childbearing potential 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

Key Exclusion Criteria for Psoriasis Subject Cohorts:

* Currently have non plaque forms of psoriasis, (eg, erythrodermic, guttate, or pustular psoriasis).
* Have current drug induced psoriasis, eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drugs or lithium
* Males of childbearing potential 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

Primary outcomes:
measure: Single Ascending Dose (SAD) Cohort: Change From Baseline in Blood Pressure at Day 1
timeFrame: Baseline, 24 hours post-dose on Day 1
measure: Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Blood Pressure at Day 10
timeFrame: Baseline, 16 hours post-dose on Day 10
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Blood Pressure at Day 28
timeFrame: Baseline, 16 hours post-dose on Day 28
measure: Single Ascending Dose (SAD) Cohort: Change From Baseline in Pulse Rate at Day 1
timeFrame: Baseline, 24 hours post-dose on Day 1
measure: Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Pulse Rate at Day 10
timeFrame: Baseline, 16 hours post-dose on Day 10
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Pulse Rate at Day 28
timeFrame: Baseline, 16 hours post-dose on Day 28
measure: Single Ascending Dose (SAD) Cohort: Change From Baseline in Oral Temperature at Day 1
timeFrame: Baseline, 24 hours post-dose on Day 1
measure: Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Oral Temperature at Day 10
timeFrame: Baseline, 16 hours post-dose on Day 10
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Oral Temperature at Day 28
timeFrame: Baseline, 16 hours post-dose on Day 28
measure: Number of Participants With Change From Baseline in Physical Examinations
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 28, MAD Psoriasis Cohort: Baseline up to Day 56, Food Effect Cohort: Baseline up to Day 37
measure: Single Ascending Dose (SAD) Cohort: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) at Day 1
timeFrame: Baseline, 24 hours post-dose on Day 1
measure: Multiple Ascending Dose (MAD) Cohort: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) at Day 10
timeFrame: Baseline, 16 hours post-dose on Day 10
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) at Day 28
timeFrame: Baseline, 16 hours post-dose on Day 28
measure: Single Ascending Dose (SAD) Cohort: Change From Baseline in Heart Rate at Day 1
timeFrame: Baseline, 24 hours post-dose on Day 1
measure: Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Heart Rate at Day 10
timeFrame: Baseline, 16 hours post-dose on Day 10
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Heart Rate at Day 28
timeFrame: Baseline, 16 hours post-dose on Day 28
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Discontinuation Due to AEs
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 28, MAD Psoriasis Cohort: Baseline up to Day 56, Food Effect Cohort: Baseline up to Day 37
measure: Number of Adverse Events (AEs) According to Severity
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 28, MAD Psoriasis Cohort: Baseline up to Day 56, Food Effect Cohort: Baseline up to Day 37
measure: Number of Participants With Laboratory Abnormalities
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 28, MAD Psoriasis Cohort: Baseline up to Day 56, Food Effect Cohort: Baseline up to Day 37
measure: Single Ascending Dose (SAD) Cohort: Change From Baseline in Creatinine Clearance at Day 1
timeFrame: Baseline, 24 hours post-dose on Day 1
measure: Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Change From Baseline in Creatinine Clearance at Day 10
timeFrame: Baseline, 16 hours post-dose on Day 10
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Creatinine Clearance at Day 28
timeFrame: Baseline, 16 hours post-dose on Day 28
measure: Food Effect Cohort: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06700841
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1
measure: Food Effect Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06700841
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1
measure: Food Effect Cohort: Maximum Observed Plasma Concentration (Cmax) of PF-06700841
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1
Secondary outcomes:
measure: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Maximum Observed Plasma Concentration (Cmax) of PF-06700841
timeFrame: SAD: pre-dose, 0.5,1,2,4,6,8,12,16,24,36,48,72,96 hour post dose on Day 1; MAD: pre-dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5,1,2,4,6,8,12,16,24 hours post dose on Day 28
measure: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06700841
timeFrame: SAD: pre-dose, 0.5,1,2,4,6,8,12,16,24,36,48,72,96 hour post dose on Day 1; MAD: pre-dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5,1,2,4,6,8,12,16,24 hours post dose on Day 28
measure: Food Effect Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF--06700841
timeFrame: Pre--dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1
measure: Single Ascending Dose (SAD) Cohort: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06700841
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post dose on Day 1
measure: Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06700841
timeFrame: MAD: pre-dose 0.5, 1, 2, 4, 6, 8, 12, 24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5,1,2,4,6,8,12,16,24 hours post dose on Day 28
measure: Single Ascending Dose (SAD) Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06700841
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post dose on Day 1
measure: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06700841
timeFrame: SAD: pre-dose, 0.5,1,2,4,6,8,12,16,24,36,48,72,96 hour post dose on Day 1; MAD: pre-dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5,1,2,4,6,8,12,16,24 hours post dose on Day 28
measure: Single Ascending Dose (SAD) Cohort: Dose Normalized Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf[dn]) of PF-06700841
timeFrame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post dose on Day 1
measure: Single Ascending Dose (SAD) Cohort: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06700841
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post dose on Day 1
measure: Multiple Ascending Dose (MAD) Cohort: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau[dn]) of PF-06700841
timeFrame: pre-dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10
measure: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Plasma Decay Half-Life (t1/2) of PF-06700841
timeFrame: SAD: pre--dose, 0.5,1,2,4,6,8,12,16,24,36,48,72,96 hour post-dose on Day 1; MAD: pre--dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10; MAD Psoriasis: pre--dose, 0.5,1,2,4,6,8,12,16,24 hours post-dose on Day 28
measure: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Mean Residence Time (MRT) of PF-06700841
timeFrame: SAD: pre--dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post-dose on Day 1; MAD: pre--dose 0.5, 1, 2, 4, 6, 8, 12, 24 hour post--dose on Day 10; MAD Psoriasis: pre--dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours post-dose on Day 28
measure: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Apparent Volume of Distribution (Vz/F) of PF-06700841
timeFrame: SAD: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post-dose on Day 1; MAD: pre-dose 0.5, 1, 2, 4, 6, 8, 12, 24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours post-dose on Day 28
measure: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Apparent Clearance (CL/F) of PF-06700841
timeFrame: SAD: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post-dose on Day 1; MAD: pre-dose 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours post-dose on Day 28
measure: Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Peak-Trough Fluctuation (PTF) of PF-06700841
timeFrame: MAD: pre--dose 0.5, 1, 2, 4, 6, 8, 12, 24 hour post--dose on Day 10; MAD Psoriasis: pre--dose, 0.5,1,2,4,6,8,12,16,24 hours post-dose on Day 28
measure: Multiple Ascending Dose (MAD) Cohort: Amount of PF-06700841 Recovered Unchanged in the Urine Over the Time Interval Tau (Aetau)
timeFrame: 0-24 hour on Day 10
measure: Multiple Ascending Dose (MAD) Cohort: Percentage of Dose of PF-06700841 Recovered Unchanged in the Urine Over the Time Interval Tau (Aetau%)
timeFrame: 0-24 hours on Day 10
measure: Multiple Ascending Dose (MAD) Cohort: Renal Clearance
timeFrame: 0-24 hours on Day 10
measure: Single Ascending Dose (SAD) Cohort: Interferon Gamma-induced Protein 10 (IP-10) Concentration in Serum at Baseline
timeFrame: Baseline
measure: Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Interferon Gamma-induced Protein 10 (IP-10) Concentration in Serum at Day 2, 5, 10, 11, 28
timeFrame: Baseline, Day 2, 5, 10, 11, 28
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Interferon Gamma-Induced Protein 10 (IP-10) Concentration in Serum at Day 2, 5, 7, 14, 21, 28, 29, 35, 56
timeFrame: Baseline, Day 2, 5, 7, 14, 21, 28, 29, 35, 56
measure: Single Ascending Dose (SAD) Cohort: High Sensitivity C-reactive Protein (hsCRP) Concentration in Serum at Baseline
timeFrame: Baseline
measure: Multiple Ascending Dose (MAD) Cohort: Change From Baseline In High Sensitivity C-reactive Protein (hsCRP) at Day 2, 5, 10, 11, 28
timeFrame: Baseline, Day 2, 5, 10, 11, 28
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline In High Sensitivity C-reactive Protein (hsCRP) at Day 2, 5, 7, 14, 21, 28, 29, 35 and 56
timeFrame: Baseline, Day 2, 5 ,7,14, 21, 28, 29, 35, 56
measure: Single Ascending Dose (SAD) Cohort: Change From Baseline in Neutrophil Counts at Day 2, 5 and 8
timeFrame: Baseline, Day 2, 5, 8
measure: Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Neutrophil Counts at Day 4, 8, 10, 11, 14, 28
timeFrame: Baseline, Day 4, 8, 10, 11, 14, 28
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Neutrophil Counts at Day 4, 6, 8, 10, 13, 14, 21, 28, 35, 42 and 56
timeFrame: Baseline, Day 4, 6 ,8,10, 13, 14, 21, 28, 35, 42, 56
measure: Single Ascending Dose (SAD) Cohort: Change From Baseline in Reticulocyte Counts at Day 2, 5, 8
timeFrame: Baseline, Day 2, 5, 8
measure: Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Reticulocyte Counts at Day 4, 8, 10, 11, 14 and 28
timeFrame: Baseline, Day 4, 8, 10, 11, 14, 28
measure: Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Reticulocyte Counts at Day 4, 6, 8, 10, 13, 14, 21, 28, 35, 42 and 56
timeFrame: Baseline, Day 4, 6 ,8,10, 13, 14, 21, 28, 35, 42, 56
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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citation: Page KM, Suarez-Farinas M, Suprun M, Zhang W, Garcet S, Fuentes-Duculan J, Li X, Scaramozza M, Kieras E, Banfield C, Clark JD, Fensome A, Krueger JG, Peeva E. Molecular and Cellular Responses to the TYK2/JAK1 Inhibitor PF-06700841 Reveal Reduction of Skin Inflammation in Plaque Psoriasis. J Invest Dermatol. 2020 Aug;140(8):1546-1555.e4. doi: 10.1016/j.jid.2019.11.027. Epub 2020 Jan 21.
citation: Banfield C, Scaramozza M, Zhang W, Kieras E, Page KM, Fensome A, Vincent M, Dowty ME, Goteti K, Winkle PJ, Peeva E. The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a TYK2/JAK1 Inhibitor (PF-06700841) in Healthy Subjects and Patients With Plaque Psoriasis. J Clin Pharmacol. 2018 Apr;58(4):434-447. doi: 10.1002/jcph.1046. Epub 2017 Dec 21.