A Study to Assess Two Forms of The Study Medicine (Ritlecitinib) in Healthy Adult Participants

Ritlecitinib is a covalent and irreversible inhibitor of JAK3 with high selectivity over the other JAK isoforms (JAK1, JAK2, and TYK2). Ritlecitinib also inhibits irreversibly the tyrosine kinase expressed in TEC family kinases with selectivity over the broader human kinome. Treatment with ritlecitinib is expected to inhibit the inflammatory pathways mediated by IL 7, IL 15 and IL 21, all implicated in UC, CD, AA, RA, and vitiligo. Moreover, due to lack of activity against the other JAK isoforms, ritlecitinib is expected to spare immunoregulatory cytokines such as IL 10, IL 27 and IL 35, which are critical to the maintenance of immunosuppressive functions and immune homeostasis.

The objective of this study is to estimate the impact of administration methods on the bioavailability of the pediatric ritlecitinib intact BiC formulation. The study will be conducted as a Phase 1, open-label, single dose, randomized, 4-crossover periods and 1-fixed period design in a single cohort of approximately 12 healthy male or female participants at a single center. Participants will be randomized into 1 of 4 sequences of treatment. Blood samples will be collected for PK analysis. A taste assessment will be also conducted.

Participants will participate in the study for up to approximately 2.5 months, with the inclusion of the screening and follow-up period. On Day 1 of each period, participants will receive a single dose of IP. Administration of IP will be via dosing using intact BiCs with water or by emptying the capsule contents on soft food as per dosing instructions.

Participants will be confined in the CRU for a total of at least 11 days and discharged at the discretion of the investigator. A follow-up phone call will be made at least 28 calendar days and up to 35 calendar days after the last administration of the study intervention to capture any potential AE and confirm appropriate contraceptive usage.

Tolerability and safety will be assessed for all treatments by monitoring AEs.

• Ritlecitinib (Drug), also known as PF-06651600: ritlecitinib 1 x 30 mg intact BiC (Treatment Arms A, E) ritlecitinib 1 x 30 mg intact BiC sprinkled on soft foods (Treatment Arms B, C, D)

Primary outcomes

• Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Ritlecitinib [0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours post-dose on Day 1 of each period. Each treatment period lasted 24 hours. Dosing of each period was separated by at least a 48-hour washout interval.]: AUCinf was defined as area under the plasma-concentration time profile from time zero extrapolated to infinite time. AUCinf for ritlecitinib was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
• Maximum Observed Concentration (Cmax) of Ritlecitinib [0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours post-dose on Day 1 of each period. Each treatment period lasted 24 hours. Dosing of each period was separated by at least a 48-hour washout interval.]: Cmax was defined as maximum observed plasma concentration. Cmax for ritlecitinib was observed directly from data.

Secondary outcomes

• Number of Participants With All-Causality and Treatment-Related Treatment Emergent Adverse Events (TEAEs) [From the first dose of study treatment up to 28-35 days after last dose of study treatment (ie, up to 45 days)]: An adverse event (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 events were events between first dose of study treatment and up to approximately 35 days that were absent before treatment or that worsened relative to pretreatment state.
• Number of Participants With Laboratory Abnormalities [From the first dose of study treatment up to 28-35 days after last dose of study treatment (ie, up to 45 days)]: Hematology included hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, etc. Chemistry included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, etc. Urinalysis included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin and microscopy. Laboratory abnormalities were judged by the investigator. Laboratory abnormalities reported for at least 1 participant in the whole study are presented here.

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Key Inclusion Criteria:

1. Aged 18 or older.
2. Male or female who are healthy as determined by medical assessment.
3. Body-mass Index (BMI) of 16 to 32, and a total body weight > 45kg.

Key Exclusion Criteria:

1. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
2. 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).
3. Known immunodeficiency disorder, including positive serology for HIV, or a first degree relative with a hereditary immunodeficiency, or infections (acute or chronic).

Participant flow

Outcome results

• Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Ritlecitinib (Primary), Geometric mean, nanogram*hour per milliliter (ng*hr/mL): Ritlecitinib 30 mg Capsule (Fasted) 389.1 +/- 32; Ritlecitinib 30 mg Capsule Mixed With Strawberry Jam (Fasted) 398.3 +/- 31; Ritlecitinib 30 mg Capsule Mixed With Yoghurt (Fasted) 378.0 +/- 27; Ritlecitinib 30 mg Capsule Mixed With Applesauce (Fasted) 387.8 +/- 27; Ritlecitinib 30 mg Capsule Given With High Fat Meal 387.0 +/- 23
• Maximum Observed Concentration (Cmax) of Ritlecitinib (Primary), Geometric mean, ng/mL: Ritlecitinib 30 mg Capsule (Fasted) 244.3 +/- 35; Ritlecitinib 30 mg Capsule Mixed With Strawberry Jam (Fasted) 236.1 +/- 28; Ritlecitinib 30 mg Capsule Mixed With Yoghurt (Fasted) 206.6 +/- 24; Ritlecitinib 30 mg Capsule Mixed With Applesauce (Fasted) 229.4 +/- 25; Ritlecitinib 30 mg Capsule Given With High Fat Meal 108.0 +/- 28
• Number of Participants With All-Causality and Treatment-Related Treatment Emergent Adverse Events (TEAEs) (Secondary), Count of participants, Participants: Ritlecitinib 30 mg Capsule (Fasted) 5; Ritlecitinib 30 mg Capsule Mixed With Strawberry Jam (Fasted) 2; Ritlecitinib 30 mg Capsule Mixed With Yoghurt (Fasted) 4; Ritlecitinib 30 mg Capsule Mixed With Applesauce (Fasted) 4; Ritlecitinib 30 mg Capsule Given With High Fat Meal 2
• Number of Participants With Laboratory Abnormalities (Secondary), Count of participants, Participants: Ritlecitinib 30 mg Capsule (Fasted) 0; Ritlecitinib 30 mg Capsule Mixed With Strawberry Jam (Fasted) 0; Ritlecitinib 30 mg Capsule Mixed With Yoghurt (Fasted) 0; Ritlecitinib 30 mg Capsule Mixed With Applesauce (Fasted) 0; Ritlecitinib 30 mg Capsule Given With High Fat Meal 0

Adverse events

Time frame: From the first dose of study treatment up to 28-35 days after last dose of study treatment (ie, up to 45 days)

Other adverse events by term

• Study Protocol (PDF, 2023-02-02)
• Statistical Analysis Plan (PDF, 2023-03-27)

• Pfizer CT.gov Call Center, Study director, Pfizer