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Recruiting NCT05588323

Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids

Phase I / Phase II Interventional Opioid-Induced Constipation (OIC)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Naldemedine.
Who it may be relevant to
Registry conditions: Opioid-Induced Constipation (OIC). Basic parameters: 2 years — 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Albania, Armenia, Belgium, Bosnia and Herzegovina, France +3
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

  • Maximum Plasma Concentration (Cmax) of Naldemedine and Nor-naldemedine [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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]
Secondary outcome measures (9)
  • Number of Participants Experiencing Treatment-emergent Adverse Events [Time frame: Day 1 through Day 7]
  • Population PK Analysis: Cmax of Naldemedine [Time frame: Day 1 through Day 7]
  • Population PK Analysis: Tmax of Naldemedine [Time frame: Day 1 through Day 7]
  • Population PK Analysis: AUC From Time Zero to tau (AUC0-tau) of Naldemedine [Time frame: 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 [Time frame: 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 [Time frame: Day 1 through Day 7]
  • Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 6 Years and Above [Time frame: Day 1 through Day 7]
  • Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 2 to Less Than 6 Years [Time frame: Day 1 through Day 7]
  • Ability to Swallow Naldemedine Tablets [Time frame: Day 1 through Day 7]

Eligibility criteria

Inclusion criteria

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.

Exclusion criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Supportive care

Study locations

France · 4 centers
  • 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
Belgium · 3 centers
  • CHU Saint-Pierre Clinical Trials Unit — Brussels
  • Universitair Ziekenhuis Brussel (UZBrussel) - Department of Anesthesiology and Perioperati — Brussels
  • University Hospitals Leuven Pediatrisch hemato-oncology — Leuven
Italy · 3 centers
  • 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 centers
  • PHI University Clinic for Children's , Surgery — Skopje
  • University Clinic for Childrens Diseases , Department of Oncology, Hematology and , Malign — Skopje
Albania · 1 center
  • University Center Mother Theresa , Hospital - Onco-hematology department — Tirana
Armenia · 1 center
  • Yeolyan Hematology. , and Oncology Center - — Yerevan
Bosnia and Herzegovina · 1 center
  • University Clinical Hospital , Mostar — Mostar
Japan · 1 center
  • National Center for Child Health and Development — Tokyo

Identifiers

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

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗