Opioid-Induced Constipation (OIC)Phase 1/2NCT05588323
Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids
A Phase 1/2 study testing Naldemedine in people with Opioid-Induced Constipation (OIC), run by Shionogi at 16 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Opioid-Induced Constipation (OIC)
- What is being tested?
- Naldemedine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 16 sitesin 8 countries
- Study dates
- 4 Jan 2023to 15 Jun 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
16 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
Shionogi Clinical Trials Administrator Clinical Support Help Line contact
16 sites in 8 countries
France4 sites
- Completed
Chu de Caen
Caen, 14033
- Completed
Hôpital Béclère Service de Pédiatrie Centre de Référence des Maladies Héréditaires du Métabolisme Hépatique (CRMHMH)
Clamart
- Completed
Hôpital Jeanne de Flandre Antenne du CIC pédiatrique - Niveau 0 CHU de Lille
Lille
- Completed
Hôpital Armand Trousseau Service Hématologie et Oncologie Pédiatrique
Paris
Belgium3 sites
- Completed
CHU Saint-Pierre Clinical Trials Unit
Brussels
- Completed
Universitair Ziekenhuis Brussel (UZBrussel) - Department of Anesthesiology and Perioperative Medicine
Brussels
- Completed
University Hospitals Leuven Pediatrisch hemato-oncology
Leuven
Italy3 sites
- Completed
Instituto Nazionale dei Tumori
Milan
- Completed
Citta della Salute e della Scienza di Torino
Torino
- Completed
Maternal and Child Health Institute IRCCS Burlo Garofolo, Pain and pediatric palliative care service
Trieste
North Macedonia2 sites, 2 recruiting
- Recruiting
PHI University Clinic for Children's , Surgery
Skopje
- Recruiting
University Clinic for Childrens Diseases , Department of Oncology, Hematology and , Malignant Hemopathy
Skopje
Albania1 site, 1 recruiting
- Not yet recruiting
University Center Mother Theresa , Hospital - Onco-hematology department
Tirana
Armenia1 site, 1 recruiting
- Recruiting
Yeolyan Hematology. , and Oncology Center -
Yerevan
Bosnia and Herzegovina1 site, 1 recruiting
- Recruiting
University Clinical Hospital , Mostar
Mostar
Japan1 site, 1 recruiting
- Not yet recruiting
National Center for Child Health and Development
Tokyo
About this study
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
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)
- Being tested
- Naldemedine
- Medical subject headings
- Opioid-Induced Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaldemedineDrug
Also called Rizmoic
Administered as an oral tablet (0.2 mg dose level only), or oral suspension (all dose levels)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Naldemedine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax) of Naldemedine and Nor-naldemedine
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Day 1 through Day 7
Population PK Analysis: Cmax of Naldemedine
Measured: Day 1 through Day 7
Population PK Analysis: Tmax of Naldemedine
Measured: Day 1 through Day 7
Population PK Analysis: AUC From Time Zero to tau (AUC0-tau) of Naldemedine
Measured: 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
Measured: 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
Measured: Day 1 through Day 7
Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 6 Years and Above
Palatability will be assessed by participant self-reporting using a visual analogue scale (VAS).
Measured: Day 1 through Day 7
Palatability of Naldemedine Powder for Oral Suspension in Participants Aged 2 to Less Than 6 Years
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.
Measured: Day 1 through Day 7
Ability to Swallow Naldemedine Tablets
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.
Measured: Day 1 through Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2022
- Study start4 Jan 2023
- Primary completion15 Jun 2028 (estimated)
- Study completion15 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid-Induced Constipation (OIC)Studies of the same condition, open and under way.
- More trials run by ShionogiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shionogi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shionogi Clinical Trials Administrator Clinical Support Help Line, Study director, Shionogi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05588323
- Sponsor's protocol ID
- 1907V921F
- Other IDs
- 2019-003577-25, 2019
- Status last verified
- Jul 2026
- First submitted
- 18 Oct 2022
- Last updated
- 28 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No