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
- Constipationobstipation10017943
- Registration Number
- NL-OMON44584
- Lead Sponsor
- Kyowa Kirin Pharmaceutical Develpment Ltd.
- Brief Summary
Trial never started
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 10
1. Written informed consent for study participation must be obtained prior to any study-related procedures being performed (local regulations are to be followed in determining the assent/consent requirements for children and parent[s]/guardian[s]) and according to international guidelines and/or applicable European Union guidelines.
2. Patients between the ages of >=6 months and <18 years
3. Patients with malignant or non-malignant pain who are receiving (or are about to receive) acute or chronic treatment with opioids
4. In the investigator's judgment, patients must be either newly diagnosed with constipation or patients must have a history of constipation treated with laxatives or be expected to develop constipation after initiation of opioid treatment.
5. Patients must have the ability to be present in the clinic for at least 10 hours following the first dose of naloxegol for PK sampling and post first dose tolerability observations and be able to return at 24 hours for PK sampling.
6. Female patients of childbearing potential must have a negative urine pregnancy test at screening. Females of childbearing potential must either not be sexually active or be using an adequate birth control method throughout the duration of the study.
7. Provision of informed consent prior to any study specific procedures
1. Involvement of a parent or guardian in the planning and/or conduct of the study (applies to both KKI staff and/or staff at the study site)
2. Previous enrolment in the present study with intake of naloxegol IP
3. Current acute or chronic use of methadone
4. For patients 6-12 months old, history of major corrective or reconstructive GI surgery (except pyloric stenosis) in the last 6 months or possible need for corrective or reconstructive GI surgery in the next month, or history of post-surgical ileus. For patients over 1 year of age, history of previous GI surgery in the last 6 months (does not include placement of enteral tubes or liver biopsies).
5. History of an intra-abdominal or peritoneal neoplasm or an ongoing GI-related issue (eg, inflammatory bowel disease, connective tissue disorders like Ehler Danlos, dermatomyositis, scleroderma) which, in the opinion of the investigator, may be contributing to constipation as a result of mechanical obstruction or may place the patient at increased risk for intestinal perforation by impairing the local or global structural integrity of the GI tract.
6. Signs or symptoms of GI obstruction including faecal impaction requiring medical intervention. History of GI obstructive conditions (eg, Hirschsprung's disease, malrotation, volvulus, pseudo-obstruction syndromes).
7. Currently active medical conditions or ongoing treatments (eg, irinotecan) that may result in diarrhoea or intermittent loose stools during the screening or treatment period.
8. Significant cardiorespiratory dysfunction or haemodynamic instability
9. Evidence of known widespread cancer metastases in the CNS
10. Radiotherapy between the diaphragm and the pelvis in the 4 weeks prior to screening or planned to be initiated during the treatment period
11. Any of the following findings and/or conditions:
(i) For patients 6 -12 months old, any elevation of serum direct or indirect bilirubin and LFTs that have not undergone a medical work up. For patients over 1 year old, serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 x upper limit of normal (ULN) and/or serum bilirubin >1.2 x ULN (unless known to be due to Gilbert*s syndrome or sickle cell disease).
(ii) Creatinine clearance <60 ml/min/1.73 m2 (using the Schwartz formula*).
(iii) Absolute neutrophil count <1.0 x 10^9/L; haemoglobin <9 g/dL (or <7 g/dL if known to be related to sickle cell disease) or, platelet count <50,000/µL. For oncology patients, excursions below these limits may be considered on a case-by-case basis following discussion between the investigator and the Medical Monitor, and agreement of the Sponsor.
12. History (within past 3 months) of prolonged (>10 days) neutropenia or thrombocytopenia with clinical sequelae.
13. Treatment with another experimental medication for which there is no current labelled therapy (adult or paediatric), currently or within the last 30 days.
14. Patients with cancer currently receiving the first cycle of chemotherapy, or due to receive a chemotherapeutic agent for the first time
15. Life expectancy of <3 months
16. Treatment within 7 days of naloxegol dosing with any concomitant medications known or expected to be significantly affected by naloxegol administration or known to significantly affect naloxegol PK (See Section 7.7.2 for list of excluded concomitant medications)
17. Patients with clinically significant BBB disruption
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To characterize the pharmacokinetics (PK) of naloxegol after single oral dose<br /><br>and through population PK in paediatric patients with opioid induced<br /><br>constipation (OIC)<br /><br><br /><br>To assess the safety and tolerability of naloxegol in paediatric OIC patients</p><br>
- Secondary Outcome Measures
Name Time Method <p>To characterize the PK of naloxegol after multiple, once-daily, oral dosing in<br /><br>paediatric OIC patients who continue participation beyond Day 1. A minimum of 3<br /><br>days of dosing is required for multiple-dose PK analysis.<br /><br><br /><br>To evaluate the acceptability of the study medication in paediatric OIC<br /><br>patients through assessment of: 1) palatability of liquid formulation and, 2)<br /><br>the ability of the patient to swallow the tablet.</p><br>