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Completed

NCT Number: NCT05128058

A Target Occupancy Study With Ritlecitinib.

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

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Key information

Conditions

Healthy

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Clinical Research Unit - New Haven

New Haven, Connecticut, 06511, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Ritlecitinib 50 mg

Drug

50 mg single dose

Other names: PF-06651600

Ritlecitinib 200 mg

Drug

200 mg single dose

Other names: PF-06651600

Primary outcomes

  1. Percent Target Occupancy for JAK3

    Time frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    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.

  2. Percent Target Occupancy for BTK

    Time frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    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.

  3. Percent Target Occupancy for ITK

    Time frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    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.

  4. Percent Target Occupancy for TXK

    Time frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    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.

  5. Percent Target Occupancy for TEC

    Time frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    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.

  6. Percent Target Occupancy for BMX

    Time frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    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.

Secondary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of Ritlecitinib

    Time frame: 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    Cmax is maximum observed plasma concentration. Cmax for ritlecitinib was observed directly from data.

  2. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ritlecitinib

    Time frame: 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    Tmax is time for Cmax. Tmax for ritlecitinib was observed directly from data as time of first occurrence.

  3. Last Quantifiable Plasma Concentration (Clast) of Ritlecitinib

    Time frame: 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    Clast is last quantifiable plasma concentration. Clast for ritlecitinib was observed directly from data.

  4. Average Plasma Concentration From Time 0 to 24 Hours (Cav) of Ritlecitinib

    Time frame: 0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose

    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.

  5. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Ritlecitinib

    Time frame: 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

    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.

  6. Area Under the Curve From Time 0 to 24 Hours (AUC24) of Ritlecitinib

    Time frame: 0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose

    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.

  7. Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs)

    Time frame: From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)

    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.

  8. Number of Participants With Treatment-Emergent Adverse Events by Severity

    Time frame: From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)

    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.

  9. Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality

    Time frame: From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)

    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.

  10. Number of Participants With Pre-defined Criteria for Vital Signs

    Time frame: From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)

    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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Nov 19, 2021
Registry last updated
Nov 13, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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