A Target Occupancy Study With Ritlecitinib.

Healthy Clinical Trial

Official title:

AN OPEN LABEL, PHASE 1, TWO-ARM STUDY TO ASSESS TARGET OCCUPANCY AND FUNCTIONAL INHIBITION OF JAK3 AND TEC KINASES BY SINGLE DOSES OF RITLECITINIB IN HEALTHY ADULT PARTICIPANTS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05128058
• Other study ID #: B7981045
• Status: Completed
• Phase: Phase 1
• Start date: October 22, 2021
• Est. completion date: January 14, 2022

Study information

• Verified date: November 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1, open label, two-arm study to assess target occupancy and functional inhibition of JAK3 and TEC kinases by Ritlecitinib in healthy adult participants

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: January 14, 2022
• Est. primary completion date: January 14, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

Participants are eligible to be included in the study only if all the following criteria

apply:

• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination including BP and pulse rate measurement, 12-lead ECG, or clinical and laboratory tests.
• BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Infection with HIV, hepatitis B or hepatitis C viruses
• Have evidence of untreated or inadequately treated active or latent Mycobacterium TB infection
• Known active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections.
• Have received only one of the 2 required doses of COVID-19 vaccine.
• Participants have a known present or a history of malignancy other than a successfully treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Ritlecitinib 50 mg
50 mg single dose
• Ritlecitinib 200 mg
200 mg single dose

Locations

Country	Name	City	State
United States	Pfizer Clinical Research Unit - New Haven	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Target Occupancy for JAK3	Target occupancy for janus kinase 3 (JAK3) in peripheral blood mononuclear cells (PBMCs) by ritlecitinib was investigated in human blood by chemical probe-based enrichment and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Primary	Percent Target Occupancy for BTK	Target occupancy for Bruton's tyrosine kinase (BTK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Primary	Percent Target Occupancy for ITK	Target occupancy forIL 2 inducible T-cell kinase (ITK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Primary	Percent Target Occupancy for TXK	Target occupancy for tyrosine kinase expressed in T cells (TXK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Primary	Percent Target Occupancy for TEC	Target occupancy for tyrosine kinase expressed carcinoma (TEC) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Primary	Percent Target Occupancy for BMX	Target occupancy for bone marrow tyrosine kinase gene in chromosome X (BMX) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point) *100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Secondary	Maximum Observed Plasma Concentration (Cmax) of Ritlecitinib	Cmax is maximum observed plasma concentration. Cmax for ritlecitinib was observed directly from data.	0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ritlecitinib	Tmax is time for Cmax. Tmax for ritlecitinib was observed directly from data as time of first occurrence.	0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Secondary	Last Quantifiable Plasma Concentration (Clast) of Ritlecitinib	Clast is last quantifiable plasma concentration. Clast for ritlecitinib was observed directly from data.	0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Secondary	Average Plasma Concentration From Time 0 to 24 Hours (Cav) of Ritlecitinib	Cav is average plasma concentration from time 0 to 24 hours over the 24 hours period. Cav for ritlecitinib was calculated as area under the plasma concentration-time curve from 0 to 24 hours (AUC24) divided by 24.	0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Ritlecitinib	AUClast is area under the plasma concentration-time profile from time 0 to the time of the Clast. AUClast for ritlecitinib was determined using linear/log trapezoidal method.	0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Secondary	Area Under the Curve From Time 0 to 24 Hours (AUC24) of Ritlecitinib	AUC24 is area under the plasma concentration-time curve from time 0 to 24 hours. AUC24 for ritlecitinib was determined using linear/log trapezoidal method.	0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose
Secondary	Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs)	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness to study treatment was assessed by the investigator. A serious adverse event (SAE) was 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 treatment and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
Secondary	Number of Participants With Treatment-Emergent Adverse Events by Severity	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness to study treatment was assessed by the investigator. Treatment-emergent are events between first dose of study treatment and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs are 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.	From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
Secondary	Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality	Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocyte, platelet, neutrophils, eosinophils, monocytes, basophils, lymphocytes, etc), chemistry (glucose, calcium, sodium, potassium, chloride, total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, etc), and urinalysis (glucose, protein, hemoglobin, ketones, nitrite, leukocytes, urine bacteria, etc). Baseline = the pre-dose measurement on Day -1. Laboratory abnormalities meeting pre-defined criteria are reported for this outcome measure. Only those categories in which at least 1 participant had data were reported. ULN=upper limit of normal. LPF=low power field.	From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
Secondary	Number of Participants With Pre-defined Criteria for Vital Signs	Pre-defined criteria included: 1) Diastolic blood pressure (DBP), a) supine DBP: less than (<) 50 mmHg, b) supine DBP: change of >= 20mmHg increase, c) supine DBP: change of >= 20mmHg decrease; 2) Systolic blood pressure (SBP), a) supine SBP: <90 mmHg, b) supine SBP: change of >=30mmHg increase, c) supine SBP: change of >=30mmHg decrease; 3) Supine pulse rate, a) <40 bpm, b) >120 bpm. mmHg=millimeters of mercury, bpm=beats per minute.	From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)

External Links

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