Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids

Официальное название

A Phase 1/2, Multicentre, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Naldemedine in Paediatric Patients Who Are Receiving or Who Are About to Receive Treatment With Opioids

Обзор

The primary objective of this study is to evaluate the pharmacokinetic (PK) profile of naldemedine and nor-naldemedine after a single oral dose of naldemedine in pediatric participants who are receiving or about to receive opioids.

Вмешательства

• Препарат Naldemedine
  Administered as an oral tablet (0.2 mg dose level only), or oral suspension (all dose levels)

Первичные конечные точки

• Maximum Plasma Concentration (Cmax) of Naldemedine and Nor-naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]
• Time to Achieve Maximum Plasma Concentration (Tmax) of Naldemedine and Nor-naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]
• Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of Naldemedine and Nor-naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]
• AUC Extrapolated From Time Zero to Infinity (AUC0-inf) of Naldemedine and Nor-naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]
• Terminal Elimination Rate Constant (λz) of Naldemedine and Nor-naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]
• Terminal Elimination Half-life (t1/2,z) of Naldemedine and Nor-naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]
• Apparent Total Clearance (CL/F) of Naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]
• Mean Residence Time (MRT) of Naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]
• Apparent Volume of Distribution in the Terminal Phase (Vz/F) of Naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]
• Metabolic Ratio of Cmax of Nor-naldemedine to Cmax of Naldemedine (MRM/U, Cmax) for Nor-naldemedine [Срок оценки: Day 1: 0.5, 1, 5, and 12 hours postdose; Day 2: 24 hours post Day 1 dose, before administering the Day 2 dose; Day 7 (Cohort 1 only): Predose and 1 hour postdose]

Вторичные конечные точки (9)

• Number of Participants Experiencing Treatment-emergent Adverse Events [Срок оценки: Day 1 through Day 7]
• Population PK Analysis: Cmax of Naldemedine [Срок оценки: Day 1 through Day 7]
• Population PK Analysis: Tmax of Naldemedine [Срок оценки: Day 1 through Day 7]
• Population PK Analysis: AUC From Time Zero to tau (AUC0-tau) of Naldemedine [Срок оценки: Day 1 through Day 7]
• Population PK Analysis: Accumulation Ratio for Cmax Calculated as Ratio of Day 7 to Day 1 Cmax (RCmax) of Naldemedine [Срок оценки: Day 1 through Day 7]
• Population PK Analysis: Accumulation Ratio for AUC Calculated as Ratio of Day 7 to Day 1 AUC (RAUC) of Naldemedine [Срок оценки: Day 1 through Day 7]
• Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 6 Years and Above [Срок оценки: Day 1 through Day 7]
• Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 2 to Less Than 6 Years [Срок оценки: Day 1 through Day 7]
• Ability to Swallow Naldemedine Tablets [Срок оценки: Day 1 through Day 7]

Критерии участия

Критерии включения

Disease Characteristics

• Participants with cancer or non-cancer pain who are receiving (or who are about to receive) acute or chronic treatment with opioids.
• Participants with either newly diagnosed constipation, a history of constipation treated with laxatives, or are expected to develop constipation after opioid treatment.
• Able to remain in the clinic for blood sampling for at least 12 hours following the first study intervention dose and are able to return for blood sampling at the 24-hour time point.

Weight

• Body mass index within approximately the 3rd to 97th percentile for their age according to the World Health Organization Child Growth Standards.

Критерии исключения

Medical Conditions

• History of a gastrointestinal (GI) neoplasm or an ongoing GI-related issue or any recent (within last 1 year) or planned GI tract surgery.
• Signs or symptoms of GI obstruction or participants with recurrent obstruction who may be at increased risk of GI perforation.
• Inability to eat/swallow or have need of a nasogastric tube.
• No bowel movements reported for 7 consecutive days at the time of obtaining informed consent or on the initial day of study intervention administration (Study Day 1).
• History of more than 1 week of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 neutropenia or thrombocytopenia with clinical sequelae.
• Participants who need mechanical ventilation.
• Severe CTCAE Grade 3 or above hepatic or renal impairment including end-stage renal disease requiring hemodialysis, as determined by the investigator.
• Progressive neurological disorders or potential disruption to the blood-brain barrier (for example, primary brain malignancies, central nervous system metastases, active multiple sclerosis, etc.) considering the risk of opioid withdrawal or reduced analgesia.

Prior/Ongoing Medications

• Currently receiving the first cycle of chemotherapy.
• Previously received naldemedine.

Other Exclusions

\- Positive pregnancy test for females of childbearing potential.

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Поддерживающая терапия

Центры проведения

Франция · 4 центра

• Chu de Caen — Caen
• Hôpital Béclère Service de Pédiatrie Centre de Référence des Maladies Héréditaires du Méta — Clamart
• Hôpital Jeanne de Flandre Antenne du CIC pédiatrique - Niveau 0 CHU de Lille — Lille
• Hôpital Armand Trousseau Service Hématologie et Oncologie Pédiatrique — Paris

Бельгия · 3 центра

• CHU Saint-Pierre Clinical Trials Unit — Brussels
• Universitair Ziekenhuis Brussel (UZBrussel) - Department of Anesthesiology and Perioperati — Brussels
• University Hospitals Leuven Pediatrisch hemato-oncology — Leuven

Италия · 3 центра

• Instituto Nazionale dei Tumori — Milan
• Citta della Salute e della Scienza di Torino — Torino
• Maternal and Child Health Institute IRCCS Burlo Garofolo, Pain and pediatric palliative ca — Trieste

North Macedonia · 2 центра

• PHI University Clinic for Children's , Surgery — Skopje
• University Clinic for Childrens Diseases , Department of Oncology, Hematology and , Malign — Skopje

Albania · 1 центр

• University Center Mother Theresa , Hospital - Onco-hematology department — Tirana

Армения · 1 центр

• Yeolyan Hematology. , and Oncology Center - — Yerevan

Bosnia and Herzegovina · 1 центр

• University Clinical Hospital , Mostar — Mostar

Япония · 1 центр

• National Center for Child Health and Development — Tokyo

Идентификаторы

NCT: NCT05588323 · 1907V921F · 2019-003577-25

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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