ETRASIMOD ARGININE for Ulcerative colitis|Immune-mediated inflammatory disorders

Inclusion criteria

• {"criterion_text":"- Healthy (as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and 12-lead ECGs) lactating women who are actively breastfeeding or expressing breast milk, who are at least 12 weeks post-partum and not currently pregnant (must have a negative pregnancy test), and must be 18 to 55 years of age, inclusive, at the time of signing the informed consent document (ICD).\n- Body mass index (BMI) of 16-35 kg/m2; and a total body weight >45 kg (99 lb).\n- Participants must be willing to temporarily discontinue breastfeeding their infants for a total of 21 days, ie, from the evening of the day before Day 1 through to 14 days after the last dose (approximately 8 AM the morning of Day 21). Participants must be willing to regularly pump breasts throughout the study and express breast milk according to a schedule designed to maintain lactation until the completion of breast milk collection."}

Exclusion criteria

• {"criterion_text":"- 1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary (such as moderate or severe chronic pulmonary disorders like asthma or chronic obstructive pulmonary disease [COPD]), gastrointestinal, cardiovascular, hepatic, neurological/psychiatric, anaphylactic, ophthalmologic disorders (such as macular edema, uveitis, retinopathy), or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).\n- 10. History of any lymphoproliferative disorder such as Epstein-Barr virus (EBV) related lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs or symptoms suggestive of current lymphatic or lymphoid disease. 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.\n- 11. Evidence of active Mycobacterium tuberculosis (TB) infection in the past. Adequately treated latent TB will be permitted.\n- 12. 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.\n- 13. Participants with ANY of the abnormalities in clinical laboratory tests at screening or Day -1, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary. - White blood cell (WBC) <3500/mm3 (<3.5 × 109 cells/L) - Absolute neutrophil count (ANC) <1500/mm3 (<1.5 × 109 cells/L) - Absolute lymphocyte count (ALC) <800/mm3 (<0.8 × 109 cells/L) - Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) level >2 × upper limit of normal (ULN) - Total bilirubin level > 1.5 × ULN; participants with a history of Gilbert’s syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN; - Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. - In the opinion of the investigator, have any clinically significant laboratory abnormality that could affect interpretation of study data or the participant’s participation in the study.\n- 2. Participants who in the last 6 months experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or New York Heart Association (NYHA) Class III/IV heart failure.\n- 3. Participants with history or presence of second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sinoatrial block.\n- 4. Resting HR <50 bpm at Screening or pre-randomization on Day 1. Measurement can be repeated up to 3 times to confirm the finding. Mean values will be used if repeated.\n- 5. Recurrent symptomatic bradycardia or recurrent cardiogenic syncope.\n- 14. A positive urine drug test. A single repeat for positive drug screen may be allowed.\n- 15. A positive pregnancy test.\n- 16. Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If systolic BP is ≥140 mm Hg or diastolic ≥90 mm Hg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant’s eligibility.\n- 17. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >470 ms, complete LBBB, signs of an acute or indeterminate age myocardial infarction, ST segment and/or T wave changes suggestive of myocardial ischemia, second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF exceeds 470 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant’s eligibility. Computer interpreted ECGs [with abnormal findings] should be overread by an investigator experienced in reading ECGs before excluding a participant.\n- 6. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).\n- 7. Known immunodeficiency disorder, including positive serology for human immunodeficiency virus (HIV), or a first degree relative with a hereditary immunodeficiency and history of organ transplant (except corneal transplant).\n- 8. History or evidence of hepatitis B or hepatitis C viruses. Hepatitis B vaccination is allowed.\n- 9. Participants with any of the acute or chronic infections or infection history."}

Primary endpoints

• {"endpoint_text":"- Breast milk etrasimod PK parameters: AUCtau, Cmax, Aebm, Aebm%, Tmax, and CLbm (if data permit).","definition_or_measurement_approach":"Evaluate amount of etrasimod secreted in human breast milk following multiple oral doses of etrasimod 2 mg at steady state in lactating women; PK parameters measured in breast milk (AUCtau, Cmax, Aebm, Aebm%, Tmax, CLbm)."}

Secondary endpoints

• {"endpoint_text":"- Plasma etrasimod PK parameters: AUCtau, Cmax, Tmax, as data permits.","definition_or_measurement_approach":"Estimate plasma pharmacokinetic parameters of etrasimod following multiple oral doses of etrasimod 2 mg at steady state in lactating women."}
• {"endpoint_text":"- MPAUCtau","definition_or_measurement_approach":""}
• {"endpoint_text":"- TEAEs, clinical laboratory tests, vital signs, and ECGs","definition_or_measurement_approach":"Characterize safety and tolerability of multiple oral doses of etrasimod 2 mg in lactating women using treatment-emergent adverse events, lab tests, vital signs, and ECGs."}
• {"endpoint_text":"- BWNID, BWNMD, and BWNIDPCM","definition_or_measurement_approach":""}

Methods

• Recruitment contact via Pfizer Clinical Research Unit (Belgium) with phone +3225567003 and email PfizerVolRecruitment@pfizer.com targeting healthy lactating women (site-specific contact provided for Belgium).

Belgium

Earliest CTIS Part Ii Submission Date

25-04-2025

Latest Decision Or Authorization Date

07-05-2025

Processing Time Days

12

Number Of Sites

1

Number Of Participants

8

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States