Evaluating the safety and effects of naldemedine in children using opioids

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

This study is testing whether a new medication called naldemedine can help children who are using opioids for pain avoid constipation and stay safe while doing so.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 2 Years to 18 Years
• Sex: All
• Sponsor: Shionogi Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 16 sites (Tirana and 15 other locations)
• Trial ID: NCT05588323 on ClinicalTrials.gov

What this trial studies

This study aims to assess the pharmacokinetic profile of naldemedine and its metabolite, nor-naldemedine, after a single oral dose in pediatric patients who are currently receiving or about to receive opioid treatment. The trial focuses on children with cancer or non-cancer pain who are at risk of developing opioid-induced constipation. Participants will be monitored for their ability to remain in the clinic for blood sampling for pharmacokinetic analysis over a 24-hour period following the dose. The study is designed to gather important safety and efficacy data for this population.

Who should consider this trial

Good fit: Ideal candidates include children with cancer or non-cancer pain who are receiving opioids and are at risk of constipation.

Not a fit: Patients with a history of gastrointestinal neoplasms or ongoing GI-related issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for managing opioid-induced constipation in pediatric patients.

How similar studies have performed: While there have been studies on naldemedine in adults, this specific approach in pediatric patients is novel and has not been extensively tested.

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.

Where this trial is running

Tirana and 15 other locations

• University Center Mother Theresa , Hospital - Onco-hematology department — Tirana, Albania (Not_yet_recruiting)
• Yeolyan Hematology. , and Oncology Center - — Yerevan, Armenia (Recruiting)
• CHU Saint-Pierre Clinical Trials Unit — Brussels, Belgium (Completed)
• Universitair Ziekenhuis Brussel (UZBrussel) - Department of Anesthesiology and Perioperative Medicine — Brussels, Belgium (Completed)
• University Hospitals Leuven Pediatrisch hemato-oncology — Leuven, Belgium (Completed)
• University Clinical Hospital , Mostar — Mostar, Bosnia and Herzegovina (Recruiting)
• Chu de Caen — Caen, France (Completed)
• Hôpital Béclère Service de Pédiatrie Centre de Référence des Maladies Héréditaires du Métabolisme Hépatique (CRMHMH) — Clamart, France (Completed)
• Hôpital Jeanne de Flandre Antenne du CIC pédiatrique - Niveau 0 CHU de Lille — Lille, France (Completed)
• Hôpital Armand Trousseau Service Hématologie et Oncologie Pédiatrique — Paris, France (Completed)
• Instituto Nazionale dei Tumori — Milan, Italy (Completed)
• Citta della Salute e della Scienza di Torino — Torino, Italy (Completed)
• Maternal and Child Health Institute IRCCS Burlo Garofolo, Pain and pediatric palliative care service — Trieste, Italy (Completed)
• National Center for Child Health and Development — Tokyo, Japan (Not_yet_recruiting)
• PHI University Clinic for Children's , Surgery — Skopje, North Macedonia (Recruiting)
• University Clinic for Childrens Diseases , Department of Oncology, Hematology and , Malignant Hemopathy — Skopje, North Macedonia (Recruiting)

Study contacts

• Study coordinator: Shionogi Clinical Trials Administrator Clinical Support Help Line

Conditions Opioid-Induced Constipation