Healthy Volunteers
Conditions
Keywords
Pharmacokinetics, Adults
Brief summary
The purpose of this study is to compare if three forms of study medicine (called ritlecitinib) get processed differently in healthy adults. This study is seeking healthy participants who have: * Aged 18 years or older; * male or female who are healthy as determined by medical assessment; * BMI of 16-32 kg/m2, and a total body weight \>45 kg (99 lb). All participants in this study will receive a ritlecitinib oral dose in three different forms (solution, capsule 1 and capsule 2). The study will take up to 2.5 months, including the screening period and follow-up phone call. Participants will have to stay at the study clinic for at least 13 days. There will be 4 periods in total for this study. On day 1 of each period, participants will take one form of Riltecitinib without food for the first three periods and with food for the last period. Participants will have blood samples taken both before and after taking ritlecitinib. A follow-up phone call will be made at 28 to 35 days after the last study period.
Detailed description
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 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 and therefore under development in these indications. 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. This study aims to investigate the pharmacokinetics (PK) and relative bioavailability of 2 new modified release (MR) capsule formulations of ritlecitinib, MR1 (release duration: 6-8 hours) and MR2 (release duration:13 15 hours) as single doses in fasted and fed conditions. This is a single dose, open-label, randomized, 4-period, 6-sequence crossover study in a single cohort of approximately 12 healthy participants randomized to one of the sequences (containing 1 solution and 2 modified release \[MR1 and MR2\] capsule formulations of ritlecitinib) described in the table below. The first 3 periods are under fasted condition and the fourth period is under fed condition to investigate the effect of food on the PK of MR1 and MR2. For a given participant, the total study duration from screening to follow-up phone call will be between approximately 8 to 11 weeks. Screening will occur within 28 days prior to the first dose of the study intervention. Each participant will go through Periods 1 through 4 and dosing in each treatment period will be separated by at least 3 days to minimize any carryover effect. Venous PK blood samples for PK analysis will be collected pre-dose and post-dose in each period.
Interventions
DRUGRitlecitinib
Ritlecitinib 100 milligrams (mg) will be provided as either solution or capsule formulation (2 capsules of 50 mg)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Male and female participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests. 2. BMI of 16-32 kg/m2, and a total body weight \>45 kg (99 lb). 3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 4. Capable of giving signed informed consent
Exclusion criteria
1. 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). 2. Participants with the acute or chronic infections or infection history 3. History of febrile illness within 5 days prior to the first dose of study intervention. 4. 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. 5. 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. 6. History of active or latent Mycobacterium TBA: participant who is currently being treated for active or latent Mycobacterium TB infection or has a history of Mycobacterium TB must be excluded from the study. 7. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition | For oral solution: Pre-dose (0 hours), 0.5, 1, 2, 3, 4, 6, 10, 12 and 24 hours post-dose on Day 1 of Period 1, 2 or 3; for MR1 and MR2 capsules: Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2 or 3 | — |
| Area Under the Plasma Concentration-Time Profile From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition | For oral solution: Pre-dose (0 hours), 0.5, 1, 2, 3, 4, 6, 10, 12 and 24 hours post-dose on Day 1 of Period 1, 2 or 3; for MR1 and MR2 capsules: Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2 or 3 | AUCinf was calculated as 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From start of study treatment up to 35 days after administration of last dose of study intervention (maximum up to 45 days) | An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Number of Participants With Clinically Significant Laboratory Test Abnormalities | From start of study treatment up to Day 3 of Period 4 (maximum up to Day 12, each Period = 3 days) | Laboratory parameters included: Hematology: lymphocytes/leukocytes, eosinophils/leukocytes greater than (\>) 1.2\*upper limit of normal (ULN) (percent \[%\]), neutrophils/leukocytes less than (\<) 0.8\*lower limit of normal (LLN) (%); Urinalysis: urine hemoglobin, nitrite greater than or equal to (\>=) 1, bacteria \> 20 (per high power field \[/HPF\]). Clinical significance was judged by investigator. |
| Cmax of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2, 3 (for fasted) or 4 (for fed) | — |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | From start of study treatment up to Day 3 of Period 4 (maximum up to Day 12, each Period = 3 days) | Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT, corrected QT (Fridericia method) (QTcF) and QRS intervals. Clinical significance was judged by investigator. |
| Number of Participants With Clinically Significant Vital Signs Abnormalities | From start of study treatment up to Day 3 of Period 4 (maximum up to Day 12, each Period = 3 days) | Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) were measured in a supine position. Criteria for vital signs included: SBP: value less than (\<) 90 millimeter of mercury (mmHg), change greater than or equal to (\>=) 30 mmHg decrease, change \>= 30 mmHg increase; DBP: value \< 50 mmHg, change \>= 20 mmHg decrease, change \>= 20 mmHg increase; PR: value \< 40 beats per minute (bpm), value \> 120 bpm. Clinical significance was judged by investigator. |
| AUCinf of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2, 3 (for fasted) or 4 (for fed) | AUCinf was calculated as 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. |
Countries
Belgium
Participant flow
Pre-assignment details
Participants received treatment in Period 1, 2 or 3 under fasted condition and in Period 4 under fed condition.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence 1: A Then B Then C Then B (Fed) Participants were randomized to receive ritlecitinib 100 mg single oral dose as oral solution \[A\] in fasted state on Day 1 of Period 1; then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR1 capsules \[B\] in fasted state on Day 1 of Period 2; then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR2 capsules \[C\] in fasted state on Day 1 of Period 3; and then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR1 capsules \[B\] in fed state of Period 4. Between 2 doses of consecutive periods there was a gap of at least 48 hours. | 2 |
| Treatment Sequence 2: B Then C Then A Then B (Fed) Participants were randomized to receive ritlecitinib 100 mg (2\*50 mg) single oral dose as MR1 capsules \[B\] in fasted state on Day 1 of Period 2; then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR2 capsules \[C\] in fasted state on Day 1 of Period 3; then ritlecitinib 100 mg single oral dose as oral solution \[A\] in fasted state on Day 1 of Period 1; and then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR1 capsules \[B\] in fed state of Period 4. Between 2 doses of consecutive periods there was a gap of at least 48 hours. | 2 |
| Treatment Sequence 3: C Then A Then B Then B (Fed) Participants were randomized to receive ritlecitinib 100 mg (2\*50 mg) single oral dose as MR2 capsules \[C\] in fasted state on Day 1 of Period 3; then ritlecitinib 100 mg single oral dose as oral solution \[A\] in fasted state on Day 1 of Period 1; then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR1 capsules \[B\] in fasted state on Day 1 of Period 2; and then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR1 capsules \[B\] in fed state of Period 4. Between 2 doses of consecutive periods there was a gap of at least 48 hours. | 2 |
| Treatment Sequence 4: A Then B Then C Then C (Fed) Participants were randomized to receive ritlecitinib 100 mg single oral dose as oral solution \[A\] in fasted state on Day 1 of Period 1; then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR1 capsules \[B\] in fasted state on Day 1 of Period 2; then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR2 capsules \[C\] in fasted state on Day 1 of Period 3; and then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR2 capsules \[C\] in fed state of Period 4. Between 2 doses of consecutive periods there was a gap of at least 48 hours. | 2 |
| Treatment Sequence 5: B Then C Then A Then C (Fed) Participants were randomized to receive ritlecitinib 100 mg (2\*50 mg) single oral dose as MR1 capsules \[B\] in fasted state on Day 1 of Period 2; then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR2 capsules \[C\] in fasted state on Day 1 of Period 3; then ritlecitinib 100 mg single oral dose as oral solution \[A\] in fasted state on Day 1 of Period 1; and then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR2 capsules \[C\] in fed state of Period 4. Between 2 doses of consecutive periods there was a gap of at least 48 hours. | 2 |
| Treatment Sequence 6: C Then A Then B Then C (Fed) Participants were randomized to receive ritlecitinib 100 mg (2\*50 mg) single oral dose as MR2 capsules \[C\] in fasted state on Day 1 of Period 3; then ritlecitinib 100 mg single oral dose as oral solution \[A\] in fasted state on Day 1 of Period 1; then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR1 capsules \[B\] in fasted state on Day 1 of Period 2; and then ritlecitinib 100 mg (2\*50 mg) single oral dose as MR2 capsules \[C\] in fed state of Period 4. Between 2 doses of consecutive periods there was a gap of at least 48 hours. | 2 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period 2 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment Sequence 1: A Then B Then C Then B (Fed) | Treatment Sequence 2: B Then C Then A Then B (Fed) | Treatment Sequence 3: C Then A Then B Then B (Fed) | Treatment Sequence 4: A Then B Then C Then C (Fed) | Treatment Sequence 5: B Then C Then A Then C (Fed) | Treatment Sequence 6: C Then A Then B Then C (Fed) | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 | 0 / 12 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 3 / 12 | 5 / 11 | 3 / 12 | 0 / 5 | 1 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 | 0 / 12 | 0 / 5 | 0 / 6 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition
AUCinf was calculated as 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.
Time frame: For oral solution: Pre-dose (0 hours), 0.5, 1, 2, 3, 4, 6, 10, 12 and 24 hours post-dose on Day 1 of Period 1, 2 or 3; for MR1 and MR2 capsules: Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2 or 3
Population: PK parameter set included all participants who had at least 1 PK parameter of interest quantified in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ritlecitinib 100 mg Oral Solution (Fasted) | Area Under the Plasma Concentration-Time Profile From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition | 1261 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
| Ritlecitinib 100 mg MR1 Capsule (Fasted) | Area Under the Plasma Concentration-Time Profile From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition | 1067 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| Ritlecitinib 100 mg MR2 Capsule (Fasted) | Area Under the Plasma Concentration-Time Profile From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition | 970.6 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 22 |
Comparison: A mixed effect model was used with sequence, period and treatment as fixed effects and participant with sequence as a random effect.90% CI: [79.11, 94.54]
Comparison: A mixed effect model was used with sequence, period and treatment as fixed effects and participant with sequence as a random effect.90% CI: [70.65, 83.9]
Primary
Maximum Observed Concentration (Cmax) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition
Time frame: For oral solution: Pre-dose (0 hours), 0.5, 1, 2, 3, 4, 6, 10, 12 and 24 hours post-dose on Day 1 of Period 1, 2 or 3; for MR1 and MR2 capsules: Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2 or 3
Population: Pharmacokinetic (PK) parameter set included all participants who had at least 1 PK parameter of interest quantified in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ritlecitinib 100 mg Oral Solution (Fasted) | Maximum Observed Concentration (Cmax) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition | 671.6 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| Ritlecitinib 100 mg MR1 Capsule (Fasted) | Maximum Observed Concentration (Cmax) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition | 145.1 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Ritlecitinib 100 mg MR2 Capsule (Fasted) | Maximum Observed Concentration (Cmax) of Ritlecitinib: MR Capsules vs Oral Solution Under Fasted Condition | 84.96 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
Comparison: A mixed effect model was used with sequence, period and treatment as fixed effects and participant with sequence as a random effect.90% CI: [19.31, 24.8]
Comparison: A mixed effect model was used with sequence, period and treatment as fixed effects and participant with sequence as a random effect.90% CI: [11.21, 14.27]
Secondary
AUCinf of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition
AUCinf was calculated as 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.
Time frame: Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2, 3 (for fasted) or 4 (for fed)
Population: PK parameter set included all participants who had at least 1 PK parameter of interest quantified in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ritlecitinib 100 mg Oral Solution (Fasted) | AUCinf of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | 1067 Nanogram*Hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 28 |
| Ritlecitinib 100 mg MR1 Capsule (Fasted) | AUCinf of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | 970.6 Nanogram*Hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 22 |
| Ritlecitinib 100 mg MR2 Capsule (Fasted) | AUCinf of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | 1168 Nanogram*Hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 20 |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | AUCinf of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | 1036 Nanogram*Hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 15 |
Comparison: A mixed effect model was used with sequence, period and treatment as fixed effects and participant with sequence as a random effect.90% CI: [96.46, 119.76]
Comparison: A mixed effect model was used with sequence, period and treatment as fixed effects and participant with sequence as a random effect.90% CI: [99.19, 121.17]
Secondary
Cmax of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition
Time frame: Pre-dose (0 hours), 1, 2, 3, 4, 6, 10, 12,16, 24, 36 and 48 hours post-dose on Day 1 of Period 1, 2, 3 (for fasted) or 4 (for fed)
Population: PK parameter set included all participants who had at least 1 PK parameter of interest quantified in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ritlecitinib 100 mg Oral Solution (Fasted) | Cmax of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | 145.1 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Ritlecitinib 100 mg MR1 Capsule (Fasted) | Cmax of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | 84.96 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Ritlecitinib 100 mg MR2 Capsule (Fasted) | Cmax of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | 177.1 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 16 |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | Cmax of Ritlecitinib: MR Capsules Under Fed vs Fasted Condition | 112.0 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 14 |
Comparison: A mixed effect model was used with sequence, period and treatment as fixed effects and participant with sequence as a random effect.90% CI: [105.16, 146.02]
Comparison: A mixed effect model was used with sequence, period and treatment as fixed effects and participant with sequence as a random effect.90% CI: [111.51, 151.06]
Secondary
Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: From start of study treatment up to 35 days after administration of last dose of study intervention (maximum up to 45 days)
Population: Safety analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ritlecitinib 100 mg Oral Solution (Fasted) | Number of Participants With Adverse Events (AEs) | 3 Participants |
| Ritlecitinib 100 mg MR1 Capsule (Fasted) | Number of Participants With Adverse Events (AEs) | 5 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fasted) | Number of Participants With Adverse Events (AEs) | 3 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | Number of Participants With Adverse Events (AEs) | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | Number of Participants With Adverse Events (AEs) | 1 Participants |
Secondary
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT, corrected QT (Fridericia method) (QTcF) and QRS intervals. Clinical significance was judged by investigator.
Time frame: From start of study treatment up to Day 3 of Period 4 (maximum up to Day 12, each Period = 3 days)
Population: Safety analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ritlecitinib 100 mg Oral Solution (Fasted) | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 1 Participants |
| Ritlecitinib 100 mg MR1 Capsule (Fasted) | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fasted) | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Test Abnormalities
Laboratory parameters included: Hematology: lymphocytes/leukocytes, eosinophils/leukocytes greater than (\>) 1.2\*upper limit of normal (ULN) (percent \[%\]), neutrophils/leukocytes less than (\<) 0.8\*lower limit of normal (LLN) (%); Urinalysis: urine hemoglobin, nitrite greater than or equal to (\>=) 1, bacteria \> 20 (per high power field \[/HPF\]). Clinical significance was judged by investigator.
Time frame: From start of study treatment up to Day 3 of Period 4 (maximum up to Day 12, each Period = 3 days)
Population: Safety analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ritlecitinib 100 mg Oral Solution (Fasted) | Number of Participants With Clinically Significant Laboratory Test Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR1 Capsule (Fasted) | Number of Participants With Clinically Significant Laboratory Test Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fasted) | Number of Participants With Clinically Significant Laboratory Test Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | Number of Participants With Clinically Significant Laboratory Test Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | Number of Participants With Clinically Significant Laboratory Test Abnormalities | 0 Participants |
Secondary
Number of Participants With Clinically Significant Vital Signs Abnormalities
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) were measured in a supine position. Criteria for vital signs included: SBP: value less than (\<) 90 millimeter of mercury (mmHg), change greater than or equal to (\>=) 30 mmHg decrease, change \>= 30 mmHg increase; DBP: value \< 50 mmHg, change \>= 20 mmHg decrease, change \>= 20 mmHg increase; PR: value \< 40 beats per minute (bpm), value \> 120 bpm. Clinical significance was judged by investigator.
Time frame: From start of study treatment up to Day 3 of Period 4 (maximum up to Day 12, each Period = 3 days)
Population: Safety analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ritlecitinib 100 mg Oral Solution (Fasted) | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR1 Capsule (Fasted) | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fasted) | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
| Ritlecitinib 100 mg MR2 Capsule (Fed) | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |