Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids

NCT05588323 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 1907V921F2019-003577-25
• Study Type: interventional
• Target: 24
• Locations: 8 countries
• Sites: 16

Brief Summary

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.

Conditions

Opioid-Induced Constipation (OIC)

Outcome Measures

Primary Outcomes (11)

• Maximum Plasma Concentration (Cmax) of Naldemedine and Nor-naldemedine

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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 AUC of Nor-naldemedine to AUC of Naldemedine (MRM/U, AUC) for Nor-naldemedine

  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 Outcomes (9)

• Number of Participants Experiencing Treatment-emergent Adverse Events

  Day 1 through Day 7

• Population PK Analysis: Cmax of Naldemedine

  Day 1 through Day 7

• Population PK Analysis: Tmax of Naldemedine

  Day 1 through Day 7

• Population PK Analysis: AUC From Time Zero to tau (AUC0-tau) of Naldemedine

  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

  Day 1 through Day 7

Study Arms (3)

Cohort 1: ≥ 12 to < 18 Years

EXPERIMENTAL

Participants will receive 0.05 milligrams (mg) to 0.2 mg naldemedine based on their body weight once daily for 7 days.

Drug: Naldemedine

Cohort 2: ≥ 6 to < 12 Years

EXPERIMENTAL

Participants will receive 0.05 mg to 0.2 mg naldemedine based on their body weight once daily for 7 days.

Drug: Naldemedine

Cohort 3: ≥ 2 to < 6 Years

EXPERIMENTAL

Participants will be enrolled in this cohort after the safety and PK data has been evaluated for cohorts 1 and 2. Participants will receive 0.05 mg to 0.2 mg naldemedine based on their body weight once daily for 7 days.

Drug: Naldemedine

Interventions

Naldemedine DRUG

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

Also known as: Rizmoic

Cohort 1: ≥ 12 to < 18 Years; Cohort 2: ≥ 6 to < 12 Years; Cohort 3: ≥ 2 to < 6 Years

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• \- Positive pregnancy test for females of childbearing potential.

Sponsors & Collaborators

• Shionogi: lead

Study Sites (16)

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, 14033, 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

MeSH Terms

Conditions

Opioid-Induced Constipation

Interventions

naldemedine

Condition Hierarchy (Ancestors)

Constipation; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Shionogi Clinical Trials Administrator Clinical Support Help Line

  Shionogi

  STUDY DIRECTOR

Central Study Contacts

Shionogi Clinical Trials Administrator Clinical Support Help Line

CONTACT

800-849-9707; Shionogiclintrials-admin@shionogi.co.jp

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 20, 2022
• Study Start: January 4, 2023
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): June 15, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BO (1); AL (1); IT (3); FR (4); AR (1); NO (2); BE (3); JP (1)