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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Ritlecitinib
* Drug: Tolbutamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ritlecitinib and tolbutamide<br>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<br>* Ritlecitinib 200 mg provided as four 50 mg oral capsules<br>* Other names: PF-06651600;Drug: Tolbutamide<br>* Tolbutamide 500 mg provided as one 500 mg oral tablet<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics (PK)