Opioid-induced constipation MedDRA version: 20.0 Level: LLT Classification code 10071128 Term: Opioid induced constipation System Organ Class: 100000004856
Conditions
Interventions
Product Name: naloxegol film-coated tablet 25 mg (as naloxegol oxalate 28.5 mg)
Product Code: n/a
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: naloxegol
CAS Number: 1354744-91-4
Curren
Sponsors
Kyowa Kirin Pharmaceutical Development Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients between the ages of = 6 months and =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
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 LFTs 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 Shwartz formula*). (c) Absolute neutrophil count (ANC) 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 disruptions (e.g., active multiple sclerosis, recent brain injury). 18. Patients with known hypersensitivity to other opioid antagonists 19. Patients with cancer-related pain who ar
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the pharmacokinetics (PK) of naloxegol after single oral dose and through population PK in paediatric patients with opioid induced constipation (OIC). ;Secondary Objective: · To characterize the PK of naloxegol after multiple, once-daily, oral dosing in paediatric OIC patients who continue participation beyond Day 1. A minimum of 3 days of dosing is required for multiple-dose PK analysis. · To evaluate the acceptability of the study medication in paediatric OIC patients through assessment of: 1) palatability of liquid formulation and, 2) the ability of the patient to swallow the tablet. ;Primary end point(s): Standard non-compartmental analysis approach: area under the plasma concentration-time curve from zero extrapolated to infinity (AUC), area under the plasma concentration-time curve from zero to the last quantifiable concentration (AUC(0-t)), maximum plasma concentration (Cmax), terminal half-life (t1/2?z), time to maximum plasma concentration (tmax), and mean residence time (MRT), oral clearance (CL/F) and apparent volume of distribution during the terminal phase (Vz/F). Population pharmacokinetic modelling approach: population estimated structural PK parameters and influence of potential covariates ;Timepoint(s) of evaluation of this end point: 24 hour PK blood sampling after first dose and on day 7 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Other additional multiple dose PK parameters, e.g., RAC(AUC) and Rac(Cmax).;Timepoint(s) of evaluation of this end point: 24 hour PK blood sampling after first dose and on day 7 | — |
Countries
Denmark, Israel, Netherlands, Norway, Spain, United Kingdom
Contacts
Public ContactDawn Spark
Kyowa Kirin Pharmaceutical Development Ltd.
Outcome results
None listed