Healthy Volunteers
Conditions
Keywords
pharmacokinetics (PK)
Brief summary
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
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.
Interventions
DRUGRitlecitinib
Ritlecitinib 200 mg provided as four 50 mg oral capsules
DRUGTolbutamide
Tolbutamide 500 mg provided as one 500 mg oral tablet
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Tolbutamide Administered With and Without Ritlecitinib | 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) | Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data. |
| Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tolbutamide Administered With and Without Ritlecitinib | 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) | AUCinf was defined as area under the plasma concentration time profile from time 0 extrapolated to infinite time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related | 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) | 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. |
Countries
United States
Participant flow
Pre-assignment details
A total of 12 participants were enrolled in the study. All participants were treated in Period 1 (tolbutamide treatment alone). Ten participants were treated in Period 2 (multiple dose ritlecitinib plus single dose tolbutamide treatment).
Participants by arm
| Arm | Count |
|---|---|
| Male Male participants were healthy adults between 18-65 years of age. No contraception methods were required for male participants in this study. | 9 |
| Female Female participants were healthy adults between 18-65 years of age. A female participant was eligible to participate if she was not pregnant or breastfeeding, and at least 1 of the following conditions applied: was not a woman of childbearing potential, OR was a woman of childbearing potential using a contraceptive method that was highly effective. | 3 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 | Adverse Event | 1 |
| Period 1 | Close contact with highly-transmissible infection | 1 |
Baseline characteristics
| Characteristic | Male | Female | Total |
|---|---|---|---|
| Age, Continuous Mean | 37.4 Years STANDARD_DEVIATION 12.57 | 48.7 Years STANDARD_DEVIATION 11.15 | 40.3 Years STANDARD_DEVIATION 12.78 |
| Age, Continuous Median | 36.0 Years | 53.0 Years | 37.0 Years |
| Age, Customized <18 | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 18-44 | 6 Participants | 1 Participants | 7 Participants |
| Age, Customized 45-64 | 3 Participants | 2 Participants | 5 Participants |
| Age, Customized >=65 | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 9 Participants | 0 Participants | 9 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 / 10 | 0 / 10 |
| other Total, other adverse events | 1 / 12 | 2 / 10 | 2 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 | 0 / 10 |
Outcome results
Primary
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.
Time frame: 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)
Population: Analysis population included all participants treated who had at least 1 concentration in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Tolbutamide | Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tolbutamide Administered With and Without Ritlecitinib | 608600 ng*hr/mL | Geometric Coefficient of Variation 20 |
| Period 2: Ritlecitinib + Tolbutamide | Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tolbutamide Administered With and Without Ritlecitinib | 586500 ng*hr/mL | Geometric Coefficient of Variation 30 |
90% CI: [92.01, 106.62]
Primary
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.
Time frame: 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)
Population: Analysis population included all participants treated who had at least 1 concentration in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Tolbutamide | Maximum Plasma Concentration (Cmax) of Tolbutamide Administered With and Without Ritlecitinib | 44240 ng/mL (nanogram/milliliter) | Geometric Coefficient of Variation 15 |
| Period 2: Ritlecitinib + Tolbutamide | Maximum Plasma Concentration (Cmax) of Tolbutamide Administered With and Without Ritlecitinib | 45740 ng/mL (nanogram/milliliter) | Geometric Coefficient of Variation 17 |
90% CI: [96.66, 109.77]
Secondary
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.
Time frame: 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)
Population: Analysis population included all participants assigned to the study intervention and who took at least 1 dose of the study intervention. Participants were analyzed according to the intervention they actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Period 1: Tolbutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related | All-Causality | 1 Participants |
| Period 1: Tolbutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related | Treatment-Related | 0 Participants |
| Period 2: Ritlecitinib + Tolbutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related | All-Causality | 2 Participants |
| Period 2: Ritlecitinib + Tolbutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related | Treatment-Related | 0 Participants |
| Period 2: Ritlecitinib + Tolbutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related | All-Causality | 2 Participants |
| Period 2: Ritlecitinib + Tolbutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related | Treatment-Related | 1 Participants |