Study to Evaluate the Effect of Multiple-Dose Ritlecitinib on the Pharmacokinetics (PK) of Tolbutamide

PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY TO ESTIMATE THE EFFECT OF MULTIPLE-DOSE RITLECITINIB (PF-06651600) ON THE PHARMACOKINETICS OF SINGLE-DOSE TOLBUTAMIDE IN HEALTHY PARTICIPANTS

This is a Phase 1, 2-period, multiple-dose, open-label, single fixed sequence study of the effect of ritlecitinib on tolbutamide pharmacokinetics in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Ritlecitinib; Drug: Tolbutamide

Detailed Description

A total of approximately 12 healthy male and/or female participants will be enrolled in the study to obtain at least 10 evaluable participants who complete the study. This is an open-label study not requiring an assessment of efficacy or pharmacodynamics markers, but it will include pharmacokinetic estimation drug-drug interactions.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and/or female participants who are healthy as determined by medical evaluation including medical history, full physical examination (including BP and pulse rate measurements), clinical laboratory tests, and 12-lead ECG.
• BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

Exclusion Criteria:

• Past/present clinically significant hematological, renal, endocrine, pulmonary, GI, CV, hepatic, psychiatric, neurological, dermatological or allergic disease (including drug allergies).
• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
• Infection with hepatitis B or C viruses.
• Participants with any of the following acute or chronic infections or infection history: any infection requiring treatment within 2 weeks prior to the start of study participation; any infection requiring hospitalization or parenteral antimicrobial therapy within 60 days of the first dose of investigational product; any infection judged to be an opportunistic infection or clinically significant within the past 6 months of the first dose of investigational product; known active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections; history of recurrent localized dermatomal herpes zoster, or history of disseminated (single episode) herpes simplex or disseminated herpes zoster.
• History of any lymphoproliferative disorder such as EBV related lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs or symptoms suggestive of current lymphatic or lymphoid disease.
• Known presence 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ritlecitinib and tolbutamide; In Period 1, participants will be dosed with a single administration of tolbutamide 500 mg tablet on Day 1. Period 1 will be immediately followed by Period 2 with no washout. In Period 2, participants will be dosed with oral 200 mg ritlecitinib QD for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of a 200 mg dose of ritlecitinib on the morning of Day 10.

Drug: Ritlecitinib; Ritlecitinib 200 mg provided as four 50 mg oral capsules; Other Names: PF-06651600; Drug: Tolbutamide; Tolbutamide 500 mg provided as one 500 mg oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Tolbutamide Administered With and Without Ritlecitinib	Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 36 hours post-dose of tolbutamide in Period 1 (Days 1 and 2) and Period 2 (Days 10 and 11)
Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tolbutamide Administered With and Without Ritlecitinib	AUCinf was defined as area under the plasma concentration time profile from time 0 extrapolated to infinite time.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 36 hours post-dose in Period 1 (Days 1 and 2) and Period 2 (Days 10 and 11)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related	An adverse event (AE) was any untoward medical occurrence in a clinical investigation where participants were administered a product; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug.	From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Actual): January 10, 2022
• Study Completion (Actual): January 10, 2022

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: pharmacokinetics (PK)
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Tolbutamide
• Other Study ID Numbers: B7981069; 2021-003611-25 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No