Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids

Opioid-Induced Constipation (OIC) Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05588323
• Other study ID #: 1907V921F
• Secondary ID: 2019-003577-25
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 4, 2023
• Est. completion date: August 13, 2024

Study information

• Verified date: February 2024
• Source: Shionogi Inc.
• Contact: Shionogi Clinical Trials Administrator Clinical Support Help Lin
• Phone: 800-849-9707
• Email: Shionogiclintrials-admin[@]shionogi.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: August 13, 2024
• Est. primary completion date: August 13, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Constipation
• Opioid-Induced Constipation
• Opioid-Induced Constipation (OIC)

Intervention

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

Locations

Country	Name	City	State
France	Chu de Caen	Caen

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Terminal Elimination Rate Constant (?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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Secondary	Number of Participants Experiencing Treatment-emergent Adverse Events		Day 1 through Day 7
Secondary	Population PK Analysis: Cmax of Naldemedine		Day 1 through Day 7
Secondary	Population PK Analysis: Tmax of Naldemedine		Day 1 through Day 7
Secondary	Population PK Analysis: AUC From Time Zero to tau (AUC0-tau) of Naldemedine		Day 1 through Day 7
Secondary	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
Secondary	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
Secondary	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).	Day 1 through Day 7
Secondary	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.	Day 1 through Day 7
Secondary	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.	Day 1 through Day 7