Clinical trial NCT05588323: Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Opioid-Induced Constipation (OIC)
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-20
Enrollment: 24
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


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.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Naldemedine and Nor-naldemedine
timeFrame: 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
measure: Time to Achieve Maximum Plasma Concentration (Tmax) of Naldemedine and Nor-naldemedine
timeFrame: 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
measure: 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
timeFrame: 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
measure: AUC Extrapolated From Time Zero to Infinity (AUC0-inf) of Naldemedine and Nor-naldemedine
timeFrame: 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
measure: Terminal Elimination Rate Constant (λz) of Naldemedine and Nor-naldemedine
timeFrame: 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
measure: Terminal Elimination Half-life (t1/2,z) of Naldemedine and Nor-naldemedine
timeFrame: 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
measure: Apparent Total Clearance (CL/F) of Naldemedine
timeFrame: 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
measure: Mean Residence Time (MRT) of Naldemedine
timeFrame: 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
measure: Apparent Volume of Distribution in the Terminal Phase (Vz/F) of Naldemedine
timeFrame: 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
measure: Metabolic Ratio of Cmax of Nor-naldemedine to Cmax of Naldemedine (MRM/U, Cmax) for Nor-naldemedine
timeFrame: 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
measure: Metabolic Ratio of AUC of Nor-naldemedine to AUC of Naldemedine (MRM/U, AUC) for Nor-naldemedine
timeFrame: 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:
measure: Number of Participants Experiencing Treatment-emergent Adverse Events
timeFrame: Day 1 through Day 7
measure: Population PK Analysis: Cmax of Naldemedine
timeFrame: Day 1 through Day 7
measure: Population PK Analysis: Tmax of Naldemedine
timeFrame: Day 1 through Day 7
measure: Population PK Analysis: AUC From Time Zero to tau (AUC0-tau) of Naldemedine
timeFrame: Day 1 through Day 7
measure: Population PK Analysis: Accumulation Ratio for Cmax Calculated as Ratio of Day 7 to Day 1 Cmax (RCmax) of Naldemedine
timeFrame: Day 1 through Day 7
measure: Population PK Analysis: Accumulation Ratio for AUC Calculated as Ratio of Day 7 to Day 1 AUC (RAUC) of Naldemedine
timeFrame: Day 1 through Day 7
measure: Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 6 Years and Above
timeFrame: Day 1 through Day 7
measure: Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 2 to Less Than 6 Years
timeFrame: Day 1 through Day 7
measure: Ability to Swallow Naldemedine Tablets
timeFrame: Day 1 through Day 7
Other outcomes:
Locations:
city: Tirana
country: Albania
facility: University Center Mother Theresa , Hospital - Onco-hematology department
city: Yerevan
country: Armenia
facility: Yeolyan Hematology. , and Oncology Center -
city: Brussels
country: Belgium
facility: CHU Saint-Pierre Clinical Trials Unit
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel (UZBrussel) - Department of Anesthesiology and Perioperative Medicine
city: Leuven
country: Belgium
facility: University Hospitals Leuven Pediatrisch hemato-oncology
city: Mostar
country: Bosnia and Herzegovina
facility: University Clinical Hospital , Mostar
city: Caen
country: France
facility: Chu de Caen
city: Clamart
country: France
facility: Hôpital Béclère Service de Pédiatrie Centre de Référence des Maladies Héréditaires du Métabolisme Hépatique (CRMHMH)
city: Lille
country: France
facility: Hôpital Jeanne de Flandre Antenne du CIC pédiatrique - Niveau 0 CHU de Lille
city: Paris
country: France
facility: Hôpital Armand Trousseau Service Hématologie et Oncologie Pédiatrique
city: Milan
country: Italy
facility: Instituto Nazionale dei Tumori
city: Torino
country: Italy
facility: Citta della Salute e della Scienza di Torino
city: Trieste
country: Italy
facility: Maternal and Child Health Institute IRCCS Burlo Garofolo, Pain and pediatric palliative care service
city: Tokyo
country: Japan
facility: National Center for Child Health and Development
city: Skopje
country: North Macedonia
facility: PHI University Clinic for Children's , Surgery
city: Skopje
country: North Macedonia
facility: University Clinic for Childrens Diseases , Department of Oncology, Hematology and , Malignant Hemopathy
Study officials:
affiliation: Shionogi
name: Shionogi Clinical Trials Administrator Clinical Support Help Line
role: STUDY_DIRECTOR
References: