Healthy Participants
Conditions
Keywords
etrasimod, adults
Brief summary
The purpose of this study is to look at how healthy adults process Etrasimod when assessed by wearable sensors. Etrasimod is taken without food and assessments taken by site staff and then by participants after training. The study is seeking participants who are: * Aged 18 or older * Male or female who are healthy as determined by medical assessment * Body-mass index (BMI) of 16 to 32, and a total body weight \> 50kg. The study will take up to 9 weeks, including the screening period. Participants will have to stay at the study clinic for at least 2 nights, in each of 2 study periods. Participants will take Etrasimod as a tablet by mouth without food. Blood samples will be taken both before and after participants take Etrasimod. Participants will also use wearable devices to assess blood pressure, heart rate and take further blood samples. A follow-up phone call will be made 20 to 27 days after the last study period.
Interventions
DRUGEtrasimod Immediate Release (IR)
An immediate release tablet
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants * BMI 16 to 32 kg/m2 * body weight more than 50kg
Exclusion criteria
* Ongoing or past history of significant medical conditions * Eye disorders such as macular edema or uveitis * Ongoing or recent infections * Use of prescription or non prescription medications within 7 days of first dose * Smoking or using nicotine products equivalent to more than 5 cigarettes per day * History of severe allergic or anaphylactic reactions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Serum Concentration-Time Profile From Time Zero to 24 Hours (AUC0-24) of Etrasimod: Tasso PK Sampling | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1 of each period | AUC0-24 was calculated as linear/log trapezoidal method. PK sampling: a) Treatment F/Reference: Tasso PK micro sampling was done by clinical research unit (CRU) staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely. |
| Area Under the Serum Concentration-Time Profile From Time 24 Hours to the Time of the Last Quantifiable Concentration (AUC24hr-last) of Etrasimod: Tasso PK Sampling | 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period | AUC24hr-last was calculated as linear/log trapezoidal method. PK sampling: a) Treatment F/Reference: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely. |
| Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Etrasimod: Tasso PK Sampling | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period | AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). Clast is the predicted plasma concentration at the last quantifiable time point and Kel is the terminal phase rate constant. PK sampling: a) Treatment F/Reference: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely. |
| Maximum Observed Concentration (Cmax) of Etrasimod: Tasso PK Sampling | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period | PK sampling: a) Treatment F/Reference: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Baseline; 1, 2, 3 ,4, 5, 6, 8 and 24 hours post-dose on Day 1 of each period | Heart rate was measured in beats per minute (beats/min). Baseline was defined as the average of triplicate electrocardiogram (ECG) HR measurements collected at pre-dose (0 hour) on Day 1 of each period. |
| Change From Baseline to Nadir in HR at Day 1 | Baseline; Anytime or latest time with minimum HR measurement taken post-dose on Day 1 of each period | Heart rate was measured in beats per minute (beats/min). Baseline was defined as the average of triplicate ECG HR measurements collected at pre-dose (0 hour) on Day 1 of each period. Nadir HR was taken as the minimum HR from all ECGs taken post-Etrasimod on day 1 of each period. If Nadir HR was attained at multiple post-dose time points on Day 1, only the latest time point was summarized. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Day 1 up to 35 days after last dose of study treatment (maximum up to 45 days) | An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of study treatment up to 35 days post last dose of study treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect. |
| AUC0-24 of Etrasimod: Tasso and Venous PK Sampling | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1 of each period | AUC0-24 was calculated as linear/log trapezoidal method. In this outcome measure, as planned, data of participants who received Etrasimod 2 mg IR tablet (Treatment A) in C5041034 study is used for comparison. PK sampling: a) Treatment F/Test: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely; c) Treatment A/Reference: Venous PK sampling from pre-dose (0 hour) till 168 hours post-dose. |
| Number of Participants With Clinically Significant Findings in Vital Signs | Day 1 up to 35 days after last dose of study treatment (maximum up to 45 days) | Vital signs included blood pressure systolic and diastolic millimeter of mercury (mmHg) and pulse rate (beats/min). Clinical significance of vital signs abnormalities was determined by the investigator. |
| Number of Participants With Clinically Significant Findings in Physical Examination | Day 1 up to 35 days after last dose of study treatment (maximum up to 45 days) | A complete physical examination test included, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief physical examination test included, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant reported symptoms. Clinical significance of physical examination abnormalities was determined by the investigator. |
| Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | From Baseline (Day 1) maximum up to Day 17 | ECG findings criteria for QT interval corrected using Fridericia's formula (QTcF) were as: 450 millisecond (msec) \< value less than equal (\<=) 480 msec, 480 msec \< value \<=500 msec, \>500 msec, 30 msec \<= change from baseline \<=60 msec, change from baseline \>60 msec. |
| Number of Participants With Clinically Significant Findings in Laboratory Abnormalities | Day 1 up to 35 days after last dose of study treatment (maximum up to 45 days) | Clinical laboratory abnormalities test criteria included, a) hematology: lymphocytes (10\^3/millimeter \[mm)\^3\]) and lymphocytes/leukocytes percentage (%) less than (\<) 0.8\* lower limit of normal (LLN), eosinophils (10\^3/mm\^3), eosinophils/leukocytes (%) and monocytes (10\^3/mm\^3) greater than (\>)1.2\* upper limit of normal (ULN); b) Urinalysis: urine glucose, ketones, urine hemoglobin and bilirubin, leukocyte esterase greater than equal to (\>=) 1. Clinical significance of laboratory abnormalities was determined by the investigator. |
| AUC24hr-last of Etrasimod: Tasso and Venous PK Sampling | 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period | AUC24hr-last was calculated as linear/log trapezoidal method. In this outcome measure, as planned, data of participants who received Etrasimod 2 mg IR tablet (Treatment A) in C5041034 study is used for comparison. PK sampling: a) Treatment F/Test: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely; c) Treatment A/Reference: Venous PK sampling from pre-dose (0 hour) till 168 hours post-dose. |
| AUCinf for Etrasimod: Tasso and Venous PK Sampling | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period | AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). Clast is the predicted plasma concentration at the last quantifiable time point and Kel is the terminal phase rate constant. PK sampling: a) Treatment F/Test: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely. c) Treatment A/Reference: Venous PK sampling from pre-dose (0 hour) till 168 hours post-dose. |
| Cmax for Etrasimod: Tasso and Venous PK Sampling | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period | PK sampling: a) Treatment F/Test: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely. c) Treatment A/Reference: Venous PK sampling from pre-dose (0 hour) till 168 hours post-dose. |
Countries
Belgium
Participant flow
Recruitment details
A total of 8 participants were enrolled in this present study.
Pre-assignment details
For secondary pharmacokinetic (PK) outcome measures' analysis, as planned, data of participants who received Etrasimod 2 mg IR tablet (Treatment A) in C5041034 study \[NCT05956002\] is used for comparison. These participants were not enrolled in the present study C5041050 \[NCT06140290\], only the relevant historical data was used for comparison as per the objectives.
Participants by arm
| Arm | Count |
|---|---|
| All Participants: Etrasimod 2mg All participants who received study treatment either in Period 1 or 2 of the study. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 |
| Period 2 | Assigned but not treated | 0 | 1 |
| Period 2 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants: Etrasimod 2mg |
|---|---|
| Age, Continuous | 42.0 Years STANDARD_DEVIATION 13.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 7 / 8 | 5 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 |
Outcome results
Primary
Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Etrasimod: Tasso PK Sampling
AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). Clast is the predicted plasma concentration at the last quantifiable time point and Kel is the terminal phase rate constant. PK sampling: a) Treatment F/Reference: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely.
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period
Population: PK parameter analysis set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Etrasimod: Tasso PK Sampling | 1503 ng*hr/mL | Geometric Coefficient of Variation 32 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Etrasimod: Tasso PK Sampling | 1652 ng*hr/mL | Geometric Coefficient of Variation 19 |
Comparison: Analysis was performed using a mixed effect model, with treatment as a fixed effect and participant as a random effect.90% CI: [105.17, 126.38]
Primary
Area Under the Serum Concentration-Time Profile From Time 24 Hours to the Time of the Last Quantifiable Concentration (AUC24hr-last) of Etrasimod: Tasso PK Sampling
AUC24hr-last was calculated as linear/log trapezoidal method. PK sampling: a) Treatment F/Reference: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely.
Time frame: 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period
Population: PK parameter analysis set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Area Under the Serum Concentration-Time Profile From Time 24 Hours to the Time of the Last Quantifiable Concentration (AUC24hr-last) of Etrasimod: Tasso PK Sampling | 768.4 ng*hr/mL | Geometric Coefficient of Variation 37 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Area Under the Serum Concentration-Time Profile From Time 24 Hours to the Time of the Last Quantifiable Concentration (AUC24hr-last) of Etrasimod: Tasso PK Sampling | 872.1 ng*hr/mL | Geometric Coefficient of Variation 16 |
Comparison: Analysis was performed using a mixed effect model, with treatment as a fixed effect and participant as a random effect.90% CI: [108.02, 134.22]
Primary
Area Under the Serum Concentration-Time Profile From Time Zero to 24 Hours (AUC0-24) of Etrasimod: Tasso PK Sampling
AUC0-24 was calculated as linear/log trapezoidal method. PK sampling: a) Treatment F/Reference: Tasso PK micro sampling was done by clinical research unit (CRU) staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely.
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1 of each period
Population: PK parameter analysis set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Area Under the Serum Concentration-Time Profile From Time Zero to 24 Hours (AUC0-24) of Etrasimod: Tasso PK Sampling | 666.4 Nanogram*hour per milliliter (ng*hr/mL ) | Geometric Coefficient of Variation 23 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Area Under the Serum Concentration-Time Profile From Time Zero to 24 Hours (AUC0-24) of Etrasimod: Tasso PK Sampling | 745.5 Nanogram*hour per milliliter (ng*hr/mL ) | Geometric Coefficient of Variation 25 |
Comparison: Analysis was performed using a mixed effect model, with treatment as a fixed effect and participant as a random effect.90% CI: [101.2, 115.94]
Primary
Maximum Observed Concentration (Cmax) of Etrasimod: Tasso PK Sampling
PK sampling: a) Treatment F/Reference: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely.
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period
Population: PK parameter analysis set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Maximum Observed Concentration (Cmax) of Etrasimod: Tasso PK Sampling | 40.65 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Maximum Observed Concentration (Cmax) of Etrasimod: Tasso PK Sampling | 44.63 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
Comparison: Analysis was performed using a mixed effect model, with treatment as a fixed effect and participant as a random effect.90% CI: [99.33, 114.73]
Secondary
AUC0-24 of Etrasimod: Tasso and Venous PK Sampling
AUC0-24 was calculated as linear/log trapezoidal method. In this outcome measure, as planned, data of participants who received Etrasimod 2 mg IR tablet (Treatment A) in C5041034 study is used for comparison. PK sampling: a) Treatment F/Test: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely; c) Treatment A/Reference: Venous PK sampling from pre-dose (0 hour) till 168 hours post-dose.
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1 of each period
Population: PK parameter analysis set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | AUC0-24 of Etrasimod: Tasso and Venous PK Sampling | 666.4 ng*hr/mL | Geometric Coefficient of Variation 23 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | AUC0-24 of Etrasimod: Tasso and Venous PK Sampling | 745.5 ng*hr/mL | Geometric Coefficient of Variation 25 |
| Etrasimod 2mg IR Tablet: Treatment A, C5041034 Study | AUC0-24 of Etrasimod: Tasso and Venous PK Sampling | 725.8 ng*hr/mL | Geometric Coefficient of Variation 21 |
Comparison: Analysis was performed using ANOVA (Analysis of variance) model with treatment as a fixed effect.90% CI: [77.76, 108.38]
Comparison: Analysis was performed using ANOVA model with treatment as a fixed effect.90% CI: [86.33, 122.19]
Secondary
AUC24hr-last of Etrasimod: Tasso and Venous PK Sampling
AUC24hr-last was calculated as linear/log trapezoidal method. In this outcome measure, as planned, data of participants who received Etrasimod 2 mg IR tablet (Treatment A) in C5041034 study is used for comparison. PK sampling: a) Treatment F/Test: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely; c) Treatment A/Reference: Venous PK sampling from pre-dose (0 hour) till 168 hours post-dose.
Time frame: 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period
Population: PK parameter analysis set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | AUC24hr-last of Etrasimod: Tasso and Venous PK Sampling | 768.4 ng*hr/mL | Geometric Coefficient of Variation 37 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | AUC24hr-last of Etrasimod: Tasso and Venous PK Sampling | 872.1 ng*hr/mL | Geometric Coefficient of Variation 16 |
| Etrasimod 2mg IR Tablet: Treatment A, C5041034 Study | AUC24hr-last of Etrasimod: Tasso and Venous PK Sampling | 890.1 ng*hr/mL | Geometric Coefficient of Variation 31 |
Comparison: Analysis was performed using ANOVA model with treatment as a fixed effect.90% CI: [69.42, 107.37]
Comparison: Analysis was performed using ANOVA model with treatment as a fixed effect.90% CI: [76.99, 124.7]
Secondary
AUCinf for Etrasimod: Tasso and Venous PK Sampling
AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). Clast is the predicted plasma concentration at the last quantifiable time point and Kel is the terminal phase rate constant. PK sampling: a) Treatment F/Test: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely. c) Treatment A/Reference: Venous PK sampling from pre-dose (0 hour) till 168 hours post-dose.
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period
Population: PK parameter analysis set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | AUCinf for Etrasimod: Tasso and Venous PK Sampling | 1503 ng*hr/mL | Geometric Coefficient of Variation 32 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | AUCinf for Etrasimod: Tasso and Venous PK Sampling | 1652 ng*hr/mL | Geometric Coefficient of Variation 19 |
| Etrasimod 2mg IR Tablet: Treatment A, C5041034 Study | AUCinf for Etrasimod: Tasso and Venous PK Sampling | 1694 ng*hr/mL | Geometric Coefficient of Variation 26 |
Comparison: Analysis was performed using ANOVA model with treatment as a fixed effect.90% CI: [73.1, 107.68]
Comparison: Analysis was performed using ANOVA model with treatment as a fixed effect.90% CI: [78.74, 120.83]
Secondary
Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1
Heart rate was measured in beats per minute (beats/min). Baseline was defined as the average of triplicate electrocardiogram (ECG) HR measurements collected at pre-dose (0 hour) on Day 1 of each period.
Time frame: Baseline; 1, 2, 3 ,4, 5, 6, 8 and 24 hours post-dose on Day 1 of each period
Population: SAS included all participants who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 1 hour | -4.9 Beats/minute | Standard Deviation 3.56 |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 5 hours | -4.6 Beats/minute | Standard Deviation 4.44 |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 3 hours | -10.8 Beats/minute | Standard Deviation 5.44 |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 6 hours | -7.0 Beats/minute | Standard Deviation 5.58 |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 2 hours | -10.8 Beats/minute | Standard Deviation 4.33 |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 8 hours | -9.0 Beats/minute | Standard Deviation 6.82 |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 4 hours | -10.8 Beats/minute | Standard Deviation 5.73 |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 24 hours | -8.4 Beats/minute | Standard Deviation 4.6 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 24 hours | -1.9 Beats/minute | Standard Deviation 5.01 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 1 hour | -3.4 Beats/minute | Standard Deviation 1.72 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 2 hours | -10.3 Beats/minute | Standard Deviation 2.75 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 3 hours | -10.9 Beats/minute | Standard Deviation 2.34 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 4 hours | -10.1 Beats/minute | Standard Deviation 3.44 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 5 hours | -2.4 Beats/minute | Standard Deviation 3.46 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 6 hours | -2.0 Beats/minute | Standard Deviation 5.92 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Change From Baseline in Heart Rate (HR) at 1, 2, 3, 4 ,5, 6, 8 and 24 Hours Post-dose on Day 1 | Change at 8 hours | -4.9 Beats/minute | Standard Deviation 4.56 |
Secondary
Change From Baseline to Nadir in HR at Day 1
Heart rate was measured in beats per minute (beats/min). Baseline was defined as the average of triplicate ECG HR measurements collected at pre-dose (0 hour) on Day 1 of each period. Nadir HR was taken as the minimum HR from all ECGs taken post-Etrasimod on day 1 of each period. If Nadir HR was attained at multiple post-dose time points on Day 1, only the latest time point was summarized.
Time frame: Baseline; Anytime or latest time with minimum HR measurement taken post-dose on Day 1 of each period
Population: SAS included all participants who took at least 1 dose of study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Change From Baseline to Nadir in HR at Day 1 | -14.1 Beats/ min | Standard Deviation 5.14 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Change From Baseline to Nadir in HR at Day 1 | -12.1 Beats/ min | Standard Deviation 2.27 |
Secondary
Cmax for Etrasimod: Tasso and Venous PK Sampling
PK sampling: a) Treatment F/Test: Tasso PK micro sampling was done by CRU staff participants at the CRU up to 24 hours post-dose and by participants 48-168 hours post-dose remotely; b) Treatment G/Test: Tasso PK micro sampling was done by participants at the CRU up to 24 hours post-dose and 48-168 hours post-dose remotely. c) Treatment A/Reference: Venous PK sampling from pre-dose (0 hour) till 168 hours post-dose.
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Day 1 of each period
Population: PK parameter analysis set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Cmax for Etrasimod: Tasso and Venous PK Sampling | 40.65 ng/mL | Geometric Coefficient of Variation 26 |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Cmax for Etrasimod: Tasso and Venous PK Sampling | 44.63 ng/mL | Geometric Coefficient of Variation 28 |
| Etrasimod 2mg IR Tablet: Treatment A, C5041034 Study | Cmax for Etrasimod: Tasso and Venous PK Sampling | 43.18 ng/mL | Geometric Coefficient of Variation 22 |
Comparison: Analysis was performed using ANOVA model with treatment as a fixed effect.90% CI: [79.01, 112.17]
Comparison: Analysis was performed using ANOVA model with treatment as a fixed effect.90% CI: [86.04, 124.16]
Secondary
Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria
ECG findings criteria for QT interval corrected using Fridericia's formula (QTcF) were as: 450 millisecond (msec) \< value less than equal (\<=) 480 msec, 480 msec \< value \<=500 msec, \>500 msec, 30 msec \<= change from baseline \<=60 msec, change from baseline \>60 msec.
Time frame: From Baseline (Day 1) maximum up to Day 17
Population: SAS included all participants who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | 480 msec < Value <= 500 msec | 0 Participants |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | 30 msec <= Change from baseline <= 60 msec | 0 Participants |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | Value > 500 msec | 0 Participants |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | Change from baseline > 60 msec | 0 Participants |
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | 450 msec < Value <= 480 msec | 1 Participants |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | Change from baseline > 60 msec | 0 Participants |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | 450 msec < Value <= 480 msec | 0 Participants |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | 480 msec < Value <= 500 msec | 0 Participants |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | Value > 500 msec | 0 Participants |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Number of Participants Categorized Per Pre-defined Electrocardiogram (ECG) Findings Criteria | 30 msec <= Change from baseline <= 60 msec | 0 Participants |
Secondary
Number of Participants With Clinically Significant Findings in Laboratory Abnormalities
Clinical laboratory abnormalities test criteria included, a) hematology: lymphocytes (10\^3/millimeter \[mm)\^3\]) and lymphocytes/leukocytes percentage (%) less than (\<) 0.8\* lower limit of normal (LLN), eosinophils (10\^3/mm\^3), eosinophils/leukocytes (%) and monocytes (10\^3/mm\^3) greater than (\>)1.2\* upper limit of normal (ULN); b) Urinalysis: urine glucose, ketones, urine hemoglobin and bilirubin, leukocyte esterase greater than equal to (\>=) 1. Clinical significance of laboratory abnormalities was determined by the investigator.
Time frame: Day 1 up to 35 days after last dose of study treatment (maximum up to 45 days)
Population: SAS included all participants who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Number of Participants With Clinically Significant Findings in Laboratory Abnormalities | 0 Participants |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Number of Participants With Clinically Significant Findings in Laboratory Abnormalities | 0 Participants |
Secondary
Number of Participants With Clinically Significant Findings in Physical Examination
A complete physical examination test included, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief physical examination test included, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant reported symptoms. Clinical significance of physical examination abnormalities was determined by the investigator.
Time frame: Day 1 up to 35 days after last dose of study treatment (maximum up to 45 days)
Population: SAS included all participants who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Number of Participants With Clinically Significant Findings in Physical Examination | 0 Participants |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Number of Participants With Clinically Significant Findings in Physical Examination | 0 Participants |
Secondary
Number of Participants With Clinically Significant Findings in Vital Signs
Vital signs included blood pressure systolic and diastolic millimeter of mercury (mmHg) and pulse rate (beats/min). Clinical significance of vital signs abnormalities was determined by the investigator.
Time frame: Day 1 up to 35 days after last dose of study treatment (maximum up to 45 days)
Population: SAS included all participants who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of study treatment up to 35 days post last dose of study treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect.
Time frame: Day 1 up to 35 days after last dose of study treatment (maximum up to 45 days)
Population: SAS included all participants who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Etrasimod 2mg (Treatment F, With Practice Session) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| Period 2: Etrasimod 2mg (Treatment G, Without Practice Session) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 5 Participants |