A Target Occupancy Study With Ritlecitinib.

NCT05128058 | Completed Phase 1 Results FDA Drug

• 1 other identifier: B7981045
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (10)

• Maximum Observed Plasma Concentration (Cmax) of Ritlecitinib

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

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

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

• Last Quantifiable Plasma Concentration (Clast) of Ritlecitinib

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

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

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

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

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

Study Arms (2)

Cohort 1

EXPERIMENTAL

Subjects will be dosed with 50 mg Ritlecitinib on Day 1 and followed up till Day 3

Drug: Ritlecitinib 50 mg

Cohort 2

EXPERIMENTAL

Subjects will be dosed with 200 mg Ritlecitinib on Day 1 and followed up till Day 3

Drug: Ritlecitinib 200 mg

Interventions

Ritlecitinib 50 mg DRUG

50 mg single dose

Also known as: PF-06651600

Cohort 1

Ritlecitinib 200 mg DRUG

200 mg single dose

Also known as: PF-06651600

Cohort 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Clinical Research Unit - New Haven

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

• Saadeddin A, Purohit V, Huh Y, Wong M, Maulny A, Dowty ME, Sagawa K. Virtual Bioequivalence Assessment of Ritlecitinib Capsules with Incorporation of Observed Clinical Variability Using a Physiologically Based Pharmacokinetic Model. AAPS J. 2024 Jan 24;26(1):17. doi: 10.1208/s12248-024-00888-9.

  PMID: 38267790 DERIVED

Related Links

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

MeSH Terms

Interventions

PF-06651600

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2021
• First Posted: November 19, 2021
• Study Start: October 22, 2021
• Primary Completion: January 14, 2022
• Study Completion: January 14, 2022
• Last Updated: November 13, 2023
• Results First Posted: November 13, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)