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Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids

Primary Purpose

Opioid-Induced Constipation (OIC)

Status

Recruiting

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

Naldemedine

About this trial

This is an interventional supportive care trial for Opioid-Induced Constipation (OIC)

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Chu de CaenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Cohort 1: ≥ 12 to < 18 Years

Cohort 2: ≥ 6 to < 12 Years

Cohort 3: ≥ 2 to < 6 Years

Arm Description

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

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

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.

Outcomes

Primary Outcome Measures

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

Time to Achieve Maximum Plasma Concentration (Tmax) of Naldemedine and Nor-naldemedine

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

AUC Extrapolated From Time Zero to Infinity (AUC0-inf) of Naldemedine and Nor-naldemedine

Terminal Elimination Rate Constant (λz) of Naldemedine and Nor-naldemedine

Terminal Elimination Half-life (t1/2,z) of Naldemedine and Nor-naldemedine

Apparent Total Clearance (CL/F) of Naldemedine

Mean Residence Time (MRT) of Naldemedine

Apparent Volume of Distribution in the Terminal Phase (Vz/F) of Naldemedine

Metabolic Ratio of Cmax of Nor-naldemedine to Cmax of Naldemedine (MRM/U, Cmax) for Nor-naldemedine

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

Secondary Outcome Measures

Number of Participants Experiencing Treatment-emergent Adverse Events

Population PK Analysis: Cmax of Naldemedine

Population PK Analysis: Tmax of Naldemedine

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

Population PK Analysis: Accumulation Ratio for Cmax Calculated as Ratio of Day 7 to Day 1 Cmax (RCmax) of Naldemedine

Population PK Analysis: Accumulation Ratio for AUC Calculated as Ratio of Day 7 to Day 1 AUC (RAUC) of Naldemedine

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).

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.

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.

Full Information

NCT ID

NCT05588323

First Posted

October 18, 2022

Last Updated

January 16, 2023

Sponsor

Shionogi

1. Study Identification

Unique Protocol Identification Number

NCT05588323

Brief Title

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

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 4, 2023 (Actual)

Primary Completion Date

August 13, 2024 (Anticipated)

Study Completion Date

August 13, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shionogi

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Opioid-Induced Constipation (OIC)

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1: ≥ 12 to < 18 Years

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 2: ≥ 6 to < 12 Years

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 3: ≥ 2 to < 6 Years

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Naldemedine

Other Intervention Name(s)

Rizmoic

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame