Healthy Participants
Conditions
Brief summary
A phase I, single dose study to test two forms of pediatric ritlecitinib compared to adult ritlecitinib in healthy adults aged 18-55 years old. Approximately 12 adults will participate for approximately 2.5 months.
Interventions
DRUGritlecitinib
30 mg intact adult capsule
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female participants who are healthy as determined by medical evaluation including a detailed medical history, complete (full) physical examination, which includes BP and pulse rate measurement, 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
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, dermatological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). * Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). * Known immunodeficiency disorder, including positive serology for HIV at screening, or a first degree relative with a hereditary immunodeficiency * Infection with hepatitis B or hepatitis C viruses. * History of any lymphoproliferative disorder * Known present or a history of malignancy other than a successfully treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for Ritlecitinib | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, and 24 hours post dose on Day 1 in each period | Plasma AUCinf for ritlecitinib is reported. AUCinf was calculated as \[AUClast+(Clast\*/kel)\], where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the Clast, Clast is the last quantifiable concentration, Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Maximum Plasma Concentration (Cmax) for Ritlecitinib | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, and 24 hours post dose on Day 1 in each period | Plasma Cmax for ritlecitinib is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Post first dose of study intervention on Period 1 Day 1 up to 35 days post last dose of study intervention on Period 3 Day 1 (maximum of 40 days) | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Treatment-emergent AEs (TEAEs) = 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. A serious AE (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-related AEs and SAEs were determined by the investigator. Severe=an event that prevents normal everyday activities. |
| Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | Baseline up to Period 3 Day 2 (maximum of 7 days) | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, etc), chemistry (fasting glucose, calcium, sodium, potassium, chloride, total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, uric acid, total protein, albumin, etc), and urinalysis (glucose, protein, blood, ketones, nitrites, leukocyte esterase, etc). Baseline = the last pre-dose measurement before Period 1 Day 1 (ie, first dose of study intervention). Laboratory abnormalities meeting pre-defined criteria are reported for this outcome measure. ULN=upper limit of normal. LLN=lower limit of normal. HPF=high-powered field. mEq=milliequivalent. L=liter. |
Countries
United States
Participant flow
Pre-assignment details
A total of 12 participants were assigned to study treatment and all the participants were treated in this study.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all participants who were assigned to study treatment. Participants assigned to treatment sequence 1 received ritlecitinib 30 mg intact adult capsule SD on Period 1 Day 1, followed by ritlecitinib 3\*10 mg pediatric capsules SD on Period 2 Day 1, and ritlecitinib 30 mg spray congealed beads SD on Period 3 Day 1. Participants assigned to treatment sequence 2 received ritlecitinib 3\*10 mg pediatric capsules SD on Period 1 Day 1, followed by ritlecitinib 30 mg intact adult capsule SD on Period 2 Day 1, and ritlecitinib 30 mg spray congealed beads SD on Period 3 Day 1. There was a at least 2-day washout between dosing. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 40.0 Years |
| Age, Customized 18-44 Years | 8 Participants |
| Age, Customized 45-64 Years | 4 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 9 Participants |
| Race/Ethnicity, Customized White | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 2 / 12 | 1 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for Ritlecitinib
Plasma AUCinf for ritlecitinib is reported. AUCinf was calculated as \[AUClast+(Clast\*/kel)\], where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the Clast, Clast is the last quantifiable concentration, Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, and 24 hours post dose on Day 1 in each period
Population: Includes all participants randomized and treated who had at least 1 of the pharmacokinetic (PK) parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for Ritlecitinib | 361.1 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 39 |
| Treatment B: Ritlecitinib 3*10 mg Pediatric Capsules | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for Ritlecitinib | 370.1 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 40 |
| Treatment C: Ritlecitinib 30 mg Spray Congealed Beads | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for Ritlecitinib | 385.1 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
Comparison: AUCinf was analyzed using a mixed effects model with sequence and treatment as fixed effects and participant within sequence as a random effect. Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% confidence intervals (CIs) were obtained from the model.90% CI: [94.21, 111.51]
Comparison: AUCinf was analyzed using a mixed effects model with sequence and treatment as fixed effects and participant within sequence as a random effect. Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% confidence intervals (CIs) were obtained from the model.90% CI: [100.07, 113.66]
Primary
Maximum Plasma Concentration (Cmax) for Ritlecitinib
Plasma Cmax for ritlecitinib is reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, and 24 hours post dose on Day 1 in each period
Population: Includes all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Maximum Plasma Concentration (Cmax) for Ritlecitinib | 197.4 ng/mL | Geometric Coefficient of Variation 38 |
| Treatment B: Ritlecitinib 3*10 mg Pediatric Capsules | Maximum Plasma Concentration (Cmax) for Ritlecitinib | 199.6 ng/mL | Geometric Coefficient of Variation 37 |
| Treatment C: Ritlecitinib 30 mg Spray Congealed Beads | Maximum Plasma Concentration (Cmax) for Ritlecitinib | 177.9 ng/mL | Geometric Coefficient of Variation 30 |
Comparison: Cmax was analyzed using a mixed effects model with sequence and treatment as fixed effects and participant within sequence as a random effect. Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% confidence intervals (CIs) were obtained from the model.90% CI: [88.25, 115.87]
Comparison: Cmax was analyzed using a mixed effects model with sequence and treatment as fixed effects and participant within sequence as a random effect. Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% confidence intervals (CIs) were obtained from the model.90% CI: [78.49, 103.44]
Secondary
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, etc), chemistry (fasting glucose, calcium, sodium, potassium, chloride, total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, uric acid, total protein, albumin, etc), and urinalysis (glucose, protein, blood, ketones, nitrites, leukocyte esterase, etc). Baseline = the last pre-dose measurement before Period 1 Day 1 (ie, first dose of study intervention). Laboratory abnormalities meeting pre-defined criteria are reported for this outcome measure. ULN=upper limit of normal. LLN=lower limit of normal. HPF=high-powered field. mEq=milliequivalent. L=liter.
Time frame: Baseline up to Period 3 Day 2 (maximum of 7 days)
Population: Includes all participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | Eosinophils/Leukocytes (%) >1.2*ULN | 1 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | Monocytes/Leukocytes (%) >1.2*ULN | 2 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | Bicarbonate (mEq/L) <0.9*LLN | 1 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | Ketones (No Unit) >=1 | 1 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | URINE Hemoglobin (No Unit) >=1 | 1 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | Nitrite (No Unit) >=1 | 1 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | Leukocyte Esterase (No Unit) >=1 | 1 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | URINE Leukocytes (/HPF) >=20 | 1 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality | Bacteria (/HPF) >20 | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Treatment-emergent AEs (TEAEs) = 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. A serious AE (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-related AEs and SAEs were determined by the investigator. Severe=an event that prevents normal everyday activities.
Time frame: Post first dose of study intervention on Period 1 Day 1 up to 35 days post last dose of study intervention on Period 3 Day 1 (maximum of 40 days)
Population: Includes all participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with AEs (All Causalities) | 2 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with AEs (Treatment Related) | 0 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with SAEs | 0 Participants |
| Treatment A: Ritlecitinib 30 mg Intact Adult Capsule | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with Severe AEs | 0 Participants |
| Treatment B: Ritlecitinib 3*10 mg Pediatric Capsules | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with Severe AEs | 0 Participants |
| Treatment B: Ritlecitinib 3*10 mg Pediatric Capsules | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with AEs (All Causalities) | 1 Participants |
| Treatment B: Ritlecitinib 3*10 mg Pediatric Capsules | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with SAEs | 0 Participants |
| Treatment B: Ritlecitinib 3*10 mg Pediatric Capsules | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with AEs (Treatment Related) | 0 Participants |
| Treatment C: Ritlecitinib 30 mg Spray Congealed Beads | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with Severe AEs | 0 Participants |
| Treatment C: Ritlecitinib 30 mg Spray Congealed Beads | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with AEs (Treatment Related) | 0 Participants |
| Treatment C: Ritlecitinib 30 mg Spray Congealed Beads | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with SAEs | 0 Participants |
| Treatment C: Ritlecitinib 30 mg Spray Congealed Beads | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Participants with AEs (All Causalities) | 1 Participants |