Opioid induced constipation MedDRA version: 20.0 Level: LLT Classification code 10071128 Term: Opioid induced constipation System Organ Class: 100000016726
Conditions
Interventions
Product Name: Naloxone Hydrochloride Prolonged Release Tablets
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Naloxone Hydrochloride Prolonged Release
Other descriptive name: NALOXONE HY
Sponsors
Develco Pharma Schweiz AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients =18 years of age with opioid induced constipation. 2. Long-term WHO step III opioid therapy for at least 3 months prior to screening for treatment of chronic non-cancer related pain. 3. Receiving a stable maintenance regimen with one long-acting oral or transdermal WHO step III opioid (except tapentadol) consisting of a total daily dose of =40 mg ME for a minimum of 4 weeks prior to screening, with no anticipated change in opioid dose requirement over the proposed trial period. 4. Symptoms of constipation with onset after the start of opioid medication for at least the last 4 weeks prior to screening, comprising: • ALL of the following: - =65 years) yes F.1.3.1 Number of subjects for this age range 448
Exclusion criteria
Exclusion criteria: 1. History of cancer in the last 2 years except basal cell carcinoma and non-metastatic squamous cell skin cancer. Patients with any malignancy in the past are eligible in case they have been continuously disease-free for at least 2 years. 2. Known or suspected reason for constipation other than OIC (e.g. idiopathic, neurological, endocrine, or metabolic). 3. Known or suspected medical conditions that might be associated with diarrhoea, intermittent loose stools or constipation, such as faecal incontinence or irritable bowel syndrome (IBS). In case of documented suspicion of IBS or justified doubts of a long ago diagnosis, the Rome IV criteria must be applied). 4. Any known or suspected gastrointestinal (GI) pathology that might increase the risk of perforation, such as chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis), acute diverticulitis or history of > 1 episode of diverticulitis, intestinal obstruction or pseudo-obstruction. 5. Any form of acute temporary or permanent GI ostomy, such as ileostomy or colostomy. 6. Renal impairment requiring any form of dialysis. 7. Known or suspected moderate-to-severe hepatic impairment (serum total bilirubin > 2 upper limit of normal (ULN) except in patients diagnosed with Gilbert’s syndrome, International Normalised Ratio (INR) > 2 ULN (except in patients on therapeutic anti-coagulation), serum albumin < 2.8 g/dL) 8. Presence of any other significant or progressive/unstable medical condition that, in the opinion of the investigator, would compromise evaluation of the trial treatment or may jeopardise patient's safety, compliance or adherence to protocol requirements, such as significant psychiatric, cardiovascular, pulmonary, metabolic, endocrine or neurological disease. 9. Any GI pathology or surgery or intractable vomiting likely to significantly influence drug absorption. 10. Inability to swallow the trial medication whole (e.g. due to dysphagia). 11. Known or suspected acute or chronic alcoholism, delirium tremens, or toxic psychosis. 12. Signs and symptoms that may be related to opioid withdrawal. 13. Use of prohibited medication or treatments as defined in the list of not allowed medication or treatments. 14. For women: Pregnancy or breast-feeding. Women of childbearing potential unable or unwilling to undergo pregnancy tests and practice acceptable contraceptive measures. For men: Men unable or unwilling to practice acceptable contraceptive measures. 15. Previous enrolment in this trial or participation in any other drug investigational trial within the past 30 days 16. Previous treatment in a clinical trial with Naloxone HCl PR Tablets (except one re-screening in this trial).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of Naloxone HCl PR Tablets administered twice daily at TDD of 24 mg and 48 mg over placebo in the treatment of opioid induced constipation (OIC) in terms of overall complete spontaneous bowel movement (CSBM) responder rates;Timepoint(s) of evaluation of this end point: At the end of the trial;Secondary Objective: 1. Weekly number of CSBMs and spontaneous bowel movements (SBMs) 2. SBMs (weekly and overall SBM responder rate) 3. Stool consistency according to Bristol Stool Form Scale (BSFS) categories 4. Constipation-related symptoms as determined by Symptoms of Defecation Score (SDS) 5. Bowel Function Index (BFI) score 6. Use of laxative rescue medication 7. Patient assessment of constipation 8. Patient assessment of quality of life 9. Patient and physician satisfaction with treatment 10. Willingness to take drug again 11. Comparison of different opioid/naloxone ratios 12. Adverse events 13. Pain intensity score 14. Analgesic rescue medication intake 15. Opioid withdrawal scales 16. Vital signs, weight, body mass index (BMI), and physical examination findings 17. Laboratory assessments (i.e., clinical chemistry, haematology, blood coagulation, and urinalysis) 18. Standard 12-lead electrocardiogram (ECG) 19. Comparison of different opioid/naloxone ratios;Primary end point(s): Proportion of overall CSBM Responders. Overall CSBM response defined as = 3 CSBMs/week and an increase of = 1 CSBM/week compared to baseline during at least 9 out of the 12 treatment weeks, including all of the last 4 weeks. For all primary and secondary endpoints, the number of (C)SBMs/week will be standardised to 7 days. The primary and selected secondary endpoints will also be reported by ratio of opioid to naloxone, expressed as opioid TDD (in ME) divided by naloxone TDD. An appropriate classification will be defined using blinded trial data prior to the finalisation of the statistical analysis plan (SAP). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: At the end of the trial;Secondary end point(s): 1. Proportion of overall SBM Responders (response defined analogously as for CSBMs). 2. Proportion of CSBM Responders by trial week, i.e. having = 3 CSBMs/week and an increase of = 1 CSBM/week compared to baseline 3. Proportion of SBM Responders by trial week (response defined analogously as for CSBMs) 4. Absolute and relative change of standardised number of CSBMs/week compared to baseline by trial week and overall 5. Absolute and relative change of standardised number of SBMs/week compared to baseline by trial week and overall 6. Change from baseline in proportion of type 1 and 2, type 3 and 4, and type 5-7 defecations per week according to BSFS by trial week and overall 7. CSBM “Sustained Response” defined as = 3 CSBMs/week and an increase of = 1 CSBM/week compared to baseline in all of the last 4 weeks 8. Absolute and relative change from baseline in each item and the total score of the SDS by trial week and overall 9. Absolute and relative change from baseline in standardised number of days per week with laxative rescue medication use during the double blind treatment phase by trial week and overall 10. Absolute and relative change from baseline in BFI score at the end of Week 1, 2, 4, 8 and 12 11. Absolute and relative change from baseline in Patient Assessment of Constipation – Symptoms (PAC-SYM) at the end of Week 4, 8 and 12 12. Absolute and relative change from baseline in Patient Assessment of Constipation - Quality Of Life (PAC-QOL) at the end of Week 4, 8 and 12 13. Absolute and relative change from baseline in EuroQol five dimensions questionnaire (EQ-5D-5L) at the end of Week 4, 8 and 12 14. Patient and physician satisfaction with treatment at the end of Week 12 15. Willingness to take drug again assessed at the end of Week 12 16. Adverse events (AEs; i.e., incidence, nature, and intensity of AEs, treatment-related AEs, serious AEs (SAEs) and AEs leading to d | — |
Countries
Bulgaria, Czech Republic, Germany, Hungary, Portugal, Serbia, Slovakia, Spain, United Kingdom
Contacts
Public ContactSponsor Clinical Team
Develco Pharma Schweiz AG
Outcome results
None listed