Safety and Pharmacokinetics Study of Naldemedine in Paedi... | NCT05588323

ID	Type	Description	Link
2019-003577-25	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	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.	Drug: Naldemedine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Naldemedine	Drug	Administered as an oral tablet (0.2 mg dose level only), or oral suspension (all dose levels)	Cohort 1: ≥ 12 to < 18 Years Cohort 2: ≥ 6 to < 12 Years

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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
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
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
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
Apparent Total Clearance (CL/F) of Naldemedine

Measure	Description	Time Frame
Number of Participants Experiencing Treatment-emergent Adverse Events		Day 1 through Day 7
Population PK Analysis: Cmax of Naldemedine		Day 1 through Day 7

Eligibility Module

Eligibility Criteria

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.

ID	Term
D003248	Constipation
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D000079524	Narcotic-Related Disorders
D019966	Substance-Related Disorders
D064419	Chemically-Induced Disorders
D001523	Mental Disorders