Opioid induced constipation MedDRA version: 20.0 Level: LLT Classification code 10071128 Term: Opioid induced constipation System Organ Class: 100000004856
Conditions
Interventions
Product Name: Naloxone Hydrochloride Prolonged Release Tablets
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Naloxone Hydrochloride Prolonged Release
CAS Number: 357-08-4
Other de
Sponsors
Develco Pharma Schweiz AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Male and female paediatric patients, from 4 years (provided that they are able to swallow the tablet) to less than 18 years of age. -Subjects with malignant or non-malignant pain who are requiring (or are about to require) short-term or long-term treatment with opioids (i.e. start of opioid treatment on the day of screening at the latest). -In the investigator’s judgement, subjects must be either newly diagnosed with OIC or subjects must have a history of OIC treated with laxatives or are expected to develop constipation after initiation of opioid treatment. -Female subjects of childbearing potential (postmenarchal) 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: 72 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Currently active medical conditions or ongoing treatments (e.g. irinotecan or any other chemotherapy) that may result in diarrhoea or intermittent loose stools or intractable vomiting during the screening or treatment period. - Evidence of impaired hepatic function (total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), or alkaline phosphatase (AP) >3 times the upper limit of normal, unless known to be due to Gilbert’s syndrome or sickle-cell disease). - Evidence of impaired renal function (glomerular filtration rate [GFR] <60 mL/min/1.73 m2, using the updated "bedside" Schwartz formula) or subjects with renal failure who are on any form of dialysis. - Any suspected or known physiologic, neurogenic, endocrinic, metabolic, anatomic or other causes of constipation, such as functional constipation, Hirschsprung’s disease, spinal or anal/rectal abnormalities, inflammatory bowel diseases, gastrointestinal perforation or obstruction, other drugs or any gastrointestinal pathology or surgery, likely to significantly influence drug absorption. Faecal impaction at screening. - Pregnancy or breast-feeding. - Any other condition of the subject that, in the opinion of the investigator, may compromise evaluation of the trial treatment or jeopardize subject’s safety, compliance or adherence to protocol requirements. - Administration of any other investigational products, currently or within the last 30 days, unless it is a labelled therapy (adult or paediatric), which is not expected to interfere with the pharmacokinetics/drug absorption of NLX HCl PR tablets. - Employees of the investigator, trial centre, sponsor, CRO and trial consultants, when employees are directly involved in the trial or other studies under the direction of this investigator or trial centre, and their family members.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterise the pharmacokinetics (PK) of naloxone-3-glucuronide (NLX-3-G) in children (4 to less than 18 years) with opioid-induced constipation (OIC) after single oral dose of one naloxone (NLX) HCl prolonged release (PR) tablet.;Secondary Objective: To assess the safety (in terms of maintenance of analgesia, occurrence of opioid withdrawal symptoms and standard safety assessments), acceptability/palatability and tolerability of NLX HCl PR tablets in children (4 to less than 18 years) with OIC. To assess the efficacy (descriptive activity; number of bowel movements (BMs), use of laxative rescue medication) of NLX HCl PR tablets in children (4 to less than 18 years) with OIC To assess the PK of naloxone (NLX) and 6ß-naloxole (NXOL) after single oral dose of one NLX HCl PR tablet, and optionally including steady state parameters for NLX 3 G, NLX and NXOL after multiple doses. ;Primary end point(s): Pharmacokinetic parameters of NLX-3-G on Day 1 after single oral dose. Blood samples for PK assessments will be taken pre-dose (prior to NLX PR intake), 30 min, 60 min, 90 min 2 hours and 9 hours (Day 1) as well as 24 hours (Day 2) after intake of NLX HCl PR tablets. The following PK parameters will be calculated for NLX-3-G: - Area under the plasma concentration time curve from the first time point [t=0] until last measured time point [t(last)] (AUC(0-t )) - Maximum plasma concentration after first dose (Cmax) - Time until Cmax (tmax) - If feasible, area under the plasma concentration-time curve from the time point [t=0] to infinity [8], (AUC(0-8) ), elimination half life t1/2 and elimination rate constant ?z. PK parameters will also be calculated normalised to body weight and normalised to IMP dose. ;Timepoint(s) of evaluation of this end point: At the end of the trial; in addition, to optionally re-evaluate sample size, an interim analysis will be performed as soon as evaluable PK data are available for approximately 50% of subjects (approximat | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Pain intensity (PI) scores assessed by the revised Faces Pain Scale (FPS-R) (daily diaries) - Acceptability/palatability assessed via questionnaire - Adverse events (AEs) reporting - Signs and symptoms of potential opioid withdrawal as assessed by site staff via modified Sophia Observation withdrawal Symptoms scale (mSOS) - Vital signs and physical examination - Standard safety laboratory evaluations - Number of bowel movements (BMs) (daily diaries) - Use of laxative rescue medication (daily diaries) - Pharmacokinetic parameters of naloxone (NLX) and 6ß-naloxole (NXOL) after single oral dose, including at least Cmax, AUC(0-t), tmax and, if feasible, AUC(0-8), t1/2 and ?z; normalised to IMP dose and body weight. - Optional: pharmacokinetic parameters at steady state (at Visit 4 or any other day of week 2-12 of the extension period) of NLX-3-G, NLX and NXOL over 12 hours after IMP administration; normalised to IMP dose and body weight. Blood samples for PK assessments will be taken pre-dose (prior to NLX PR intake) as well as 30 min, 60 min, 2 hours, 4 hours and 12 hours after IMP intake (but still prior to next IMP intake).;Timepoint(s) of evaluation of this end point: At the end of the trial. | — |
Countries
Czech Republic, Germany, Hungary
Contacts
Public ContactSponsor Clinical Team
Develco Pharma Schweiz AG
Outcome results
None listed