A Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06700841, With Bioavailability/Food Effect Investigation

NCT02310750 | Completed Phase 1 Results

• 1 other identifier: B7931001
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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).

Conditions

Plaque Psoriasis

Outcome Measures

Primary Outcomes (25)

• Single Ascending Dose (SAD) Cohort: Change From Baseline in Blood Pressure at Day 1

  Baseline, 24 hours post-dose on Day 1

• Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Blood Pressure at Day 10

  Baseline, 16 hours post-dose on Day 10

• Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Blood Pressure at Day 28

  Baseline, 16 hours post-dose on Day 28

• Single Ascending Dose (SAD) Cohort: Change From Baseline in Pulse Rate at Day 1

  Baseline, 24 hours post-dose on Day 1

• Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Pulse Rate at Day 10

  Baseline, 16 hours post-dose on Day 10

• Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Pulse Rate at Day 28

  Baseline, 16 hours post-dose on Day 28

• Single Ascending Dose (SAD) Cohort: Change From Baseline in Oral Temperature at Day 1

  Baseline, 24 hours post-dose on Day 1

• Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Oral Temperature at Day 10

  Baseline, 16 hours post-dose on Day 10

• Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Oral Temperature at Day 28

  Baseline, 16 hours post-dose on Day 28

• Number of Participants With Change From Baseline in Physical Examinations

  Physical examinations included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems.

  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

• 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

  Baseline, 24 hours post-dose on Day 1

• 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

  Baseline, 16 hours post-dose on Day 10

• 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

  Baseline, 16 hours post-dose on Day 28

• Single Ascending Dose (SAD) Cohort: Change From Baseline in Heart Rate at Day 1

  Baseline, 24 hours post-dose on Day 1

• Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Heart Rate at Day 10

  Baseline, 16 hours post-dose on Day 10

• Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Heart Rate at Day 28

  Baseline, 16 hours post-dose on Day 28

• Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Discontinuation Due to AEs

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug up to the end of study (up to Day 8 in SAD cohort, Day 28 in MAD cohort, Day 56 in MAD Psoriasis cohort, Day 37 in Food effect cohort), that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAE and non-SAE.

  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

• Number of Adverse Events (AEs) According to Severity

  An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs were classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.

  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

• Number of Participants With Laboratory Abnormalities

  Criteria for abnormality:hematology: hemoglobin, hematocrit, red blood cell count: less than(\<) 0.8\*lower limit of normal (LLN); mean corpuscular volume; mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration: \<0.9\*LLN,\>1.1\*upper limit of normal (ULN); platelets: \<0.5\*LLN,\>1.75\*ULN, white blood cell count: \<0.6\*LLN, \>1.5\*ULN; lymphocytes, total neutrophils: \<0.8\*LLN, \>1.2\*ULN; eosinophils, basophils, monocytes: \>1.2\*ULN; coagulation: activated partial thromboplastin time, prothrombin, prothrombin international ratio: \>1.1\*ULN; liver function: bilirubin: \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: \>3.0\*ULN; protein, albumin: \<0.8\*LLN\>\</0\>1.2\*ULN; renal function:blood urea nitrogen,creatinine: \>1.3\*ULN; uric acid: \>1.2\*ULN; electrolytes: sodium, potassium, chloride, calcium, bicarbonate: \<0.9\*LLN,\>1.1\*ULN; urinalysis: pH\<4.5, \>8; glucose, protein, blood, ketones, urobilinogen, bilirubin, nitrite; Other(glucose: \<0.6\*LLN,\>1.5\*ULN)

  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

• Single Ascending Dose (SAD) Cohort: Change From Baseline in Creatinine Clearance at Day 1

  Creatinine clearance is a measure of kidney function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time.

  Baseline, 24 hours post-dose on Day 1

• Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Change From Baseline in Creatinine Clearance at Day 10

  Creatinine clearance is a measure of kidney function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time.

  Baseline, 16 hours post-dose on Day 10

• Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Creatinine Clearance at Day 28

  Creatinine clearance is a measure of kidney function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time.

  Baseline, 16 hours post-dose on Day 28

• Food Effect Cohort: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06700841

  AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1

• Food Effect Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06700841

  Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast).

  pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1

• Food Effect Cohort: Maximum Observed Plasma Concentration (Cmax) of PF-06700841

  pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1

Secondary Outcomes (30)

• Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Maximum Observed Plasma Concentration (Cmax) of PF-06700841

  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

• Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06700841

  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

• Food Effect Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF--06700841

  Pre--dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1

• Single Ascending Dose (SAD) Cohort: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06700841

  pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post dose on Day 1

• Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06700841

  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

Study Arms (3)

PF-06700841 Oral Solution/Suspension

EXPERIMENTAL

Drug: PF-06700841 oral solution/suspension

PF-06700841 Tablet

EXPERIMENTAL

Drug: PF-06700841 tablet

Placebo

PLACEBO COMPARATOR

Oral placebo comparator for the healthy subject single and multiple ascending dose periods, and the psoriasis multiple dose period. No placebo used for the bioavailability investigation.

Other: Placebo

Interventions

PF-06700841 oral solution/suspension DRUG

Oral solution or suspension of study drug PF-06700841 (once daily or twice daily during multiple dosing periods)

PF-06700841 Oral Solution/Suspension

Placebo OTHER

Matching placebo given during the single ascending and multiple dose periods

Placebo

PF-06700841 tablet DRUG

PF-06700841 tablet formulation administered during the bioavailability / food effect investigation

PF-06700841 Tablet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

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)
• 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
• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Related Publications (3)

• Hughes JH, Qiu R, Banfield C, Dowty ME, Nicholas T. Population Pharmacokinetics of Oral Brepocitinib in Healthy Volunteers and Patients. Clin Pharmacol Drug Dev. 2022 Dec;11(12):1447-1456. doi: 10.1002/cpdd.1163. Epub 2022 Aug 31.

  PMID: 36045513 DERIVED

• 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.

  PMID: 31972249 DERIVED

• 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.

  PMID: 29266308 DERIVED

Related Links

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

MeSH Terms

Interventions

PF-06700841; 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_Inquires@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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: December 8, 2014
• Study Start: November 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: February 1, 2016
• Last Updated: March 8, 2017
• Results First Posted: March 8, 2017

Record last verified: 2017-01

Locations

US (1)