Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids

Shionogi

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Opioid-Induced Constipation (OIC)

Treatments: Drug: Naldemedine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05588323

1907V921F

2019-003577-25 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 24 estimated patients

Sex: All

Ages: 2 to 18 years old

Volunteers: No 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.

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Cohort 1: ≥ 12 to < 18 Years

Experimental group

Description:

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

Treatment:

Drug: Naldemedine

Cohort 2: ≥ 6 to < 12 Years

Experimental group

Description:

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

Treatment:

Drug: Naldemedine

Cohort 3: ≥ 2 to < 6 Years

Experimental group

Description:

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.

Treatment:

Drug: Naldemedine