Phase I Pharmacokinetics and Safety Study of Naloxegol in Paediatric OIC Patients

Study Overview
=================
Brief Summary
-----------------
To characterize the pharmacokinetics (PK) of naloxegol after single oral dose and through population PK in paediatric patients with opioid induced constipation (OIC) or at risk of OIC.

Official Title
-----------------
A Phase I, Open-Label, Multicentre Study to Assess the Pharmacokinetics and Safety of Naloxegol in Paediatric Patients Ages ≥ 6 Months to < 18 Years Receiving Treatment With Opioids

Conditions
-----------------
Constipation, Signs and Symptoms, Digestive

Intervention / Treatment
-----------------
* Drug: Naloxegol


Participation Criteria
=================
Eligibility Criteria
-----------------
Main inclusion criteria, patient with: malignant or non-malignant pain who are receiving or (are about to receive) acute or chronic treatment with opioids newly diagnosed constatipation, with history of constipation treated with laxatives or expected to develop constipation after opioid treatment ability to be present in the clinic for at least 10 hours following the first study drug for blood sampling and to return at 24 hours for blood sampling. Main exclusion criteria: Current acute or chronic use of methadone History of an neoplasm or an ongoing gastrointestinal-related issue Signs or symptoms of gastrointestinal obstruction History of prolonged neutropenia or thrombocytopenia with clinical sequelae. Patients currently receiving the first cycle of chemotherapy

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Age group: > = 12y to < 18y - Lower dose<br>Naloxegol Dose equivalent to 12.5mg in adults which will be administered once daily for up to 6 months. | Drug: Naloxegol<br>* Opioid Antagonist<br>* Other names: Moventig;|
| Experimental: Age group: > = 12y to < 18y - Higher dose<br>Naloxegol Dose equivalent to 25mg in adults which will be administered once daily for up to 6 months. | Drug: Naloxegol<br>* Opioid Antagonist<br>* Other names: Moventig;|
| Experimental: Age group: > = 6y to < 12y - Lower dose<br>Naloxegol Dose equivalent to 12.5mg in adults which will be administered once daily for up to 6 months. | Drug: Naloxegol<br>* Opioid Antagonist<br>* Other names: Moventig;|
| Experimental: Age group: > = 6y to < 12y - Higher dose<br>Naloxegol Dose equivalent to 25mg in adults which will be administered once daily for up to 6 months. | Drug: Naloxegol<br>* Opioid Antagonist<br>* Other names: Moventig;|
| Experimental: Age group: > = 6mo to < 6y - Lower dose<br>Naloxegol Dose equivalent to 12.5mg in adults which will be administered once daily for up to 6 months. | Drug: Naloxegol<br>* Opioid Antagonist<br>* Other names: Moventig;|
| Experimental: Age group: > = 6mo to < 6y - Higher dose<br>Naloxegol Dose equivalent to 25mg in adults which will be administered once daily for up to 6 months. | Drug: Naloxegol<br>* Opioid Antagonist<br>* Other names: Moventig;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterise the pharmacokinetics of naloxegol after single oral dose and through population pharmacokinetics in paediatric patients with opioid induced constipation |  | Day 1 : Pre-dose (within 30 min prior to drug dosing), 0.5, 1, 2, 4, 6, 8, 10 and 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterise the pharmacokinetics of naloxegol after multiple, once-daily, oral dosing in paediatric opioid induced constipation patients who continue participation beyond Day 1 |  | Day 7 (minimum 3 days of naloxegol treatment): pre-dose and 4 hours post-dose | 
| Palatability of naloxegol liquid drug formulation |  | Day 1 and Day 2 after dose | 
| Ability of the patient to swallow the tablet |  | Day 1 and Day 2 after dose | 
| Clinical outcome measures by assessment of laxative use |  | From Day 1 until the End of treatment (26 week of study) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Opioids, Constipation, Colonic Inertia, Dyschezia, Pharmacokinetics, Naloxegol, Paediatric, Opioid induced constipation, OIC, Phase 1