Open-label study to assess the PK and safety of naloxegol in paediatric patients receiving opioids

Phase 1

• Conditions: Opioid-induced constipation; MedDRA version: 20.0Level: LLTClassification code 10071128Term: Opioid induced constipationSystem Organ Class: 100000004856; Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

• Registration Number: EUCTR2013-003935-32-NO
• Lead Sponsor: Kyowa Kirin Pharmaceutical Development Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-10-30
• Last Update Posted: 10 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

- Patients between the ages of = 6 months and < 18 years.
- Patients with malignant or non-malignant pain who are receiving (or are about to receive) acute or chronic treatment with opioids.
- 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 are expected to develop constipation after initiation of opioid treatment.
- 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 48
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

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 investigational product.
3. Current acute or chronic use of methadone.
4. For patients 6-12 months old, history of major corrective or reconstructive gastrointestinal surgery (except pyloric stenosis) in the last 6 months or possible need for corrective or reconstructive gastrointestinal surgery in the next month, or history of post-surgical ileus. For patients over 1 year of age, history of previous gastrointestinal 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 (e.g., 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 (e.g. Hirschsprung’s disease, malrotation, volvulus, pseudo-obstruction syndromes).
7. Currently active medical conditions or ongoing treatments (e.g. 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:
(a) For patients 6 -12 months old, any elevation of serum direct or indirect bilirubin and/or elevation of LFTs not associated with their underlying disease and associated treatment that have not undergone a medical work up. For patients over 1 year old, serum ALT or 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).
(b)Creatinine clearance less than 60 ml/min/1.73 m2 (using the Schwartz formula).
(c) Absolute neutrophil count (ANC) <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/uL at the time of the first dose of naloxegol. For oncology patients, excursions below these limits may be considered on a case-by-case basis following discussions between the investigator and the Medical Monitor and the 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified