Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids
- Registration Number
- NCT05588323
- Lead Sponsor
- Shionogi
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: ≥ 12 to < 18 Years Naldemedine Participants will receive 0.05 milligrams (mg) to 0.2 mg naldemedine based on their body weight once daily for 7 days. Cohort 2: ≥ 6 to < 12 Years Naldemedine Participants will receive 0.05 mg to 0.2 mg naldemedine based on their body weight once daily for 7 days. Cohort 3: ≥ 2 to < 6 Years Naldemedine 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.
- Primary Outcome Measures
Name Time Method 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 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 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 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 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 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 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 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
- Secondary Outcome Measures
Name Time Method Number of Participants Experiencing Treatment-emergent Adverse Events Day 1 through Day 7 Population PK Analysis: Tmax of Naldemedine Day 1 through Day 7 Population PK Analysis: Cmax 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 Population PK Analysis: AUC From Time Zero to tau (AUC0-tau) of Naldemedine 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 Day 1 through Day 7 Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 6 Years and Above Day 1 through Day 7 Palatability will be assessed by participant self-reporting using a visual analogue scale (VAS).
Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 2 to Less Than 6 Years Day 1 through Day 7 Palatability will be assessed by the investigator or a participant's parent/legal guardian and, if possible, by participant self-reporting using a VAS with facial hedonic scale.
Ability to Swallow Naldemedine Tablets Day 1 through Day 7 Ability to swallow will be assessed by self-reported ease of swallowing after the first dose. Willingness to swallow will be assessed based on the participant's behavior indicative of a negative response and the response to the taste of naldemedine powder for oral suspension formulation compared to the participant's response to all other oral medications currently being given.
Trial Locations
- Locations (16)
University Center Mother Theresa , Hospital - Onco-hematology department
🇦🇱Tirana, Albania
Yeolyan Hematology. , and Oncology Center -
🇦🇲Yerevan, Armenia
CHU Saint-Pierre Clinical Trials Unit
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Brussel (UZBrussel) - Department of Anesthesiology and Perioperative Medicine
🇧🇪Brussels, Belgium
University Hospitals Leuven Pediatrisch hemato-oncology
🇧🇪Leuven, Belgium
University Clinical Hospital , Mostar
🇧🇦Mostar, Bosnia and Herzegovina
Hôpital Béclère Service de Pédiatrie Centre de Référence des Maladies Héréditaires du Métabolisme Hépatique (CRMHMH)
🇫🇷Clamart, France
Hôpital Jeanne de Flandre Antenne du CIC pédiatrique - Niveau 0 CHU de Lille
🇫🇷Lille, France
Hôpital Armand Trousseau Service Hématologie et Oncologie Pédiatrique
🇫🇷Paris, France
Instituto Nazionale dei Tumori
🇮🇹Milan, Italy
Citta della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Maternal and Child Health Institute IRCCS Burlo Garofolo, Pain and pediatric palliative care service
🇮🇹Trieste, Italy
National Center for Child Health and Development
🇯🇵Tokyo, Japan
PHI University Clinic for Children's , Surgery
🇲🇰Skopje, North Macedonia
University Clinic for Childrens Diseases , Department of Oncology, Hematology and , Malignant Hemopathy
🇲🇰Skopje, North Macedonia
Chu de Caen
🇫🇷Caen, France