Single and Multiple Ascending Doses of NTX-253 in Healthy Participants and Participants With Stable Schizophrenia

Официальное название

A First in Human, Phase 1/1b Study of Single and Multiple Ascending Dosing Administration of NTX110253 in Healthy Participants and Participants With Stable Schizophrenia

Обзор

This study will assess the safety, tolerability, and pharmacokinetics of NTX-253 following oral administration in both healthy adult participants as well as adult participants with stable schizophrenia.

Подробное описание

This study will assess the safety, tolerability, and pharmacokinetics of NTX-253 following oral administration in both healthy adult participants as well as adult participants with stable schizophrenia. NTX-253 is an investigational drug being developed for the treatment of schizophrenia. The study will consist of a single ascending dose (SAD - Part 1a) phase which will include a food effect cohort, and a cerebrospinal fluid (CSF - Part 1b) cohort in healthy volunteers. Participants will receive a single dose of either oral NTX-253 or placebo. The multiple ascending dose (MAD - Part 2) phase will follow. In Part 2, participants will be dosed for 10 consecutive days with either NTX-253 or placebo. Each phase will include sequential escalating doses in healthy volunteers. Two cohorts in the MAD phase will include stable schizophrenic adult participants who have had antipsychotic medication withdrawn for up to 8 days prior to dosing with NTX-253.

Вмешательства

• Препарат NTX-253
  Oral Capsule
• Препарат Placebo
  Oral capsule

Первичные конечные точки

• Number of reported Adverse Events [Срок оценки: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).]
• Number of Adverse Events of Special Interest (AESI) [Срок оценки: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).]
• Number of dose limiting treatment emergent adverse events (TEAE) [Срок оценки: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).]
• Vital Signs: Change in blood pressure [Срок оценки: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).]
• Vital Signs: Change in temperature [Срок оценки: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).]
• Vital Signs: Change in respiratory rate [Срок оценки: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).]
• Vital Signs: Change in heart rate [Срок оценки: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).]
• Change in physical examination [Срок оценки: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).]
• Clinical Laboratory Tests [Срок оценки: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).]

Вторичные конечные точки (9)

• Maximum observed plasma concentration (Cmax) [Pharmacokinetics] [Срок оценки: From baseline until up to 168 hours after a single dose, or until up to 168 hours after the last dose in the multiple dose cohorts.]
• Time of Cmax (tmax) [Pharmacokinetics] [Срок оценки: From baseline until up to 168 hours after a single dose, or until up to 168 hours after the last dose in the multiple dose cohorts.]
• Apparent terminal half-life (t1/2) [Срок оценки: From baseline until up to 168 hours after a single dose, or until up to 168 hours after the last dose in the multiple dose cohorts.]
• Amount of unchanged drug excreted in urine (Ae) [urinary excretion) [Срок оценки: From baseline until 72 hours after a single dose, or until the last dosing on Day 10 in the multiple dose cohort.]
• Percent of dose excreted as unchanged drug in urine (Ae%) [urinary excretion] [Срок оценки: From baseline until 72 hours after a single dose, or until the last dosing on Day 10 in the multiple dose cohort.]
• Renal clearance (Clr) [urinary excretion] [Срок оценки: From baseline until 72 hours after a single dose, or until the last dosing on Day 10 in the multiple dose cohort.]
• Maximum observed CSF concentration (Cmax, CSF) [Pharmacokinetics] [Срок оценки: From baseline until 12 hours after a single dose.]
• Time corresponding to Cmax (Tmax, CSF) [Pharmacokinetics] [Срок оценки: From baseline until 12 hours after a single dose.]
• QT/QTc potential interval prolongation and plasma concentration [Срок оценки: From baseline until 72 hours post-dose in the single dose cohorts, then from baseline until Day 13 in the multiple dose cohorts.]

Критерии участия

Primary Inclusion Criteria:

• Male or non-pregnant, non-lactating female participants, ages 18-55 who are not of childbearing potential, with a truly abstinent lifestyle, or agrees to use medically acceptable forms of birth control
• Part 1 a/b, Part 2 Cohort 7 only: Body mass index (BMI) within the range ≥18.0 to ≤30.0 kg/m2
• Participants in the food effect cohort must be willing to eat a single high fat breakfast
• (Part 2 only): Stable schizophrenia participants (schizophrenia cohorts only)
• Body mass index (BMI) within the range ≥17.5 to ≤36.0 kg/m2
• Positive and Negative Syndrome Scale (PANSS) total score <80 at screening

Primary Exclusion Criteria:

• (Part 1a/b, Part 2 Healthy): History of or current clinically significant medical or mental illness
• Cancer diagnosis/treatment in the past 7 years
• Acute or chronic gastrointestinal conditions that would interfere with drug tolerance or absorption
• Any clinically significant, abnormal 12 lead ECG
• Part 2: Any primary DSM-5TR disorder other than schizophrenia
• Participants with schizophrenia who are considered resistant/refractory to antipsychotic treatment by history; history of clozapine use.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Collaborative Neuroscience Research, LLC - CenExel — Los Alamitos

Идентификаторы

NCT: NCT07344948 · NTX-0253-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗