Naloxone HCl PR Tablets in Patients With Opioid Induced Constipation (Naxos)
Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre, Phase III Trial to Investigate the Efficacy, Safety and Tolerability of Naloxone HCl PR Tablets in Patients With Opioid Induced Constipation
Prospective, randomised, double-blind, double-dummy, placebo-controlled, parallel-group, multi-centre, phase III trial of Naloxone HCl PR Tablets (12 mg and 24 mg) administered twice daily.
The trial will consist of four phases:
Screening phase (Week -4 to Week -3):
Confirmation phase (Week -2 to Week -1):
Double-blind treatment phase
Follow-up phase (Week 13-14):
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Plovdiv, Bulgaria
- Recruiting
- Plovdiv
-
Sevlievo, Bulgaria
- Recruiting
- Sevlievo
-
Sofia, Bulgaria
- Recruiting
- Sofia
-
Veliko Tarnovo, Bulgaria
- Recruiting
- Veliko Tarnovo
-
-
-
-
-
Choceň, Czechia
- Recruiting
- Chocen
-
Hradec Králové, Czechia
- Recruiting
- Hradec Kralove
-
Liberec, Czechia
- Recruiting
- Liberec
-
Most, Czechia
- Recruiting
- Most
-
Ostrava, Czechia
- Recruiting
- Ostrava
-
Plzen, Czechia
- Recruiting
- Plzeň
-
Praha 10, Czechia
- Recruiting
- Praha 10
-
Sokolov, Czechia
- Recruiting
- Sokolov
-
Uherské Hradiště, Czechia
- Recruiting
- Uherské Hradiště
-
Zlín, Czechia
- Recruiting
- Zlin
-
Znojmo, Czechia
- Recruiting
- Znojmo
-
České Budějovice, Czechia
- Recruiting
- České Budějovice
-
-
-
-
-
Bad Honnef, Germany
- Recruiting
- Bad Honnef
-
Bad Pyrmont, Germany
- Recruiting
- Bad Pyrmont
-
Berlin, Germany
- Recruiting
- Berlin
-
Bonn, Germany
- Recruiting
- Bonn
-
Böhlen, Germany
- Recruiting
- Böhlen
-
Eichstätt, Germany
- Recruiting
- Eichstätt
-
Fellbach, Germany
- Recruiting
- Fellbach
-
Göppingen, Germany
- Recruiting
- Göppingen
-
Hamburg, Germany
- Recruiting
- Hamburg
-
Jahnsdorf, Germany
- Recruiting
- Jahnsdorf
-
Kevelaer, Germany
- Recruiting
- Kevelaer
-
Marburg, Germany
- Recruiting
- Marburg
-
Münster, Germany
- Recruiting
- Munster
-
Stadtroda, Germany
- Recruiting
- Stadtroda
-
Würzburg, Germany
- Recruiting
- Würzburg
-
-
-
-
-
Białystok, Poland
- Recruiting
- Bialystok
-
Bielsko-Biala, Poland
- Recruiting
- Bielsko-Biala
-
Bydgoszcz, Poland
- Recruiting
- Bydgoszcz
-
Gdańsk, Poland
- Recruiting
- Gdańsk
-
Katowice, Poland
- Recruiting
- Katowice
-
Kraków, Poland
- Recruiting
- Krakow
-
Ostrowiec Świętokrzyski, Poland
- Recruiting
- Ostrowiec Swietokrzyski
-
Rzeszów, Poland
- Recruiting
- Rzeszów
-
Tarnów, Poland
- Recruiting
- Tarnow
-
Tychy, Poland
- Recruiting
- Tychy
-
Warszawa, Poland
- Recruiting
- Warszawa
-
Włocławek, Poland
- Recruiting
- Wloclawek
-
Łódź, Poland
- Recruiting
- Lodz
-
-
-
-
-
Amadora, Portugal
- Recruiting
- Amadora
-
Aveiro, Portugal
- Recruiting
- Aveiro
-
Braga, Portugal
- Recruiting
- Braga
-
Covilhã, Portugal
- Recruiting
- Covilhã
-
Guimarães, Portugal
- Recruiting
- Guimarães
-
Leiria, Portugal
- Recruiting
- Leiria
-
Matosinhos, Portugal
- Recruiting
- Matosinhos
-
Setúbal, Portugal
- Recruiting
- Setúbal
-
-
-
-
-
Belgrade, Serbia
- Recruiting
- Belgrade
-
Kragujevac, Serbia
- Recruiting
- Kragujevac
-
Niš, Serbia
- Recruiting
- Niš
-
Novi Sad, Serbia
- Recruiting
- Novi Sad
-
Sombor, Serbia
- Recruiting
- Sombor
-
Sremska Kamenica, Serbia
- Recruiting
- Sremska Kamenica
-
Subotica, Serbia
- Recruiting
- Subotica
-
Vrbas, Serbia
- Recruiting
- Vrbas
-
Zrenjanin, Serbia
- Recruiting
- Zrenjanin
-
-
-
-
-
Banská Bystrica, Slovakia
- Recruiting
- Banska Bystrica
-
Bojnice, Slovakia
- Recruiting
- Bojnice
-
Bratislava, Slovakia
- Recruiting
- Bratislava
-
Dolný Kubín, Slovakia
- Recruiting
- Dolný Kubín
-
Košice, Slovakia
- Recruiting
- Kosice
-
Prešov, Slovakia
- Recruiting
- Presov
-
Rimavská Sobota, Slovakia
- Recruiting
- Rimavská Sobota
-
Žilina, Slovakia
- Recruiting
- Zilina
-
-
-
-
-
Barcelona, Spain
- Recruiting
- Barcelona
-
Granada, Spain
- Recruiting
- Granada
-
Madrid, Spain
- Recruiting
- Madrid
-
Manises, Spain
- Recruiting
- Manises
-
Palma De Mallorca, Spain
- Recruiting
- Palma
-
Santiago De Compostela, Spain
- Recruiting
- Santiago de Compostela
-
Torrejón De Ardoz, Spain
- Recruiting
- Torrejón de Ardoz
-
-
-
-
-
Aberdeen, United Kingdom
- Recruiting
- Aberdeen
-
Addlestone, United Kingdom
- Recruiting
- Addlestone
-
Belfast, United Kingdom
- Recruiting
- Belfast
-
Chesterfield, United Kingdom
- Recruiting
- Chesterfield
-
Clevedon, United Kingdom
- Recruiting
- Clevedon
-
Cockermouth, United Kingdom
- Recruiting
- Cockermouth
-
Corby, United Kingdom
- Recruiting
- Corby
-
Dunfermline, United Kingdom
- Recruiting
- Dunfermline
-
Durham, United Kingdom
- Recruiting
- Durham
-
Fowey, United Kingdom
- Recruiting
- Fowey
-
Guildford, United Kingdom
- Recruiting
- Guildford
-
Kenilworth, United Kingdom
- Recruiting
- Kenilworth
-
Leicester, United Kingdom
- Recruiting
- Leicester
-
Macclesfield, United Kingdom
- Recruiting
- Macclesfield
-
Margate, United Kingdom
- Recruiting
- Margate
-
Middlesbrough, United Kingdom
- Recruiting
- Middlesborough
-
Middlesex, United Kingdom
- Recruiting
- Middlesex
-
Newcastle Upon Tyne, United Kingdom
- Recruiting
- Newcastle-Upon-Tyne
-
Northwood, United Kingdom
- Recruiting
- Northwood
-
Penzance, United Kingdom
- Recruiting
- Penzance
-
Plymouth, United Kingdom
- Recruiting
- Plymouth
-
Romford, United Kingdom
- Recruiting
- Romford
-
Salford, United Kingdom
- Recruiting
- Salford
-
Sidcup, United Kingdom
- Recruiting
- Sidcup
-
Sunderland, United Kingdom
- Recruiting
- Sunderland
-
Thornton-Cleveleys, United Kingdom
- Recruiting
- Thornton-Cleveleys
-
Wellingborough, United Kingdom
- Recruiting
- Wellingborough
-
Wokingham, United Kingdom
- Recruiting
- Wokingham
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female patients ≥18 years of age with opioid induced constipation.
- Long-term WHO step III opioid therapy for at least 3 months prior to screening for treatment of chronic non-cancer related pain.
- 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.
- Symptoms of constipation with onset after the start of opioid medication for at least the last 4 weeks prior to screening,
Exclusion Criteria:
1. Hypersensitivity or intolerance to any active substance (i.e., naloxone, bisacodyl) or any of the excipients of the trial medication (e.g. patients with hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption). Hypersensitivity or intolerance to methylnaltrexone or naloxegol.
2. 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.
3. Known or suspected reason for constipation other than OIC (e.g. idiopathic, neurological, endocrine, or metabolic).
4. 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).
5. 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.
6. Any form of acute temporary or permanent GI ostomy, such as ileostomy or colostomy.
7. Renal impairment requiring any form of dialysis. 8. 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) 9. 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.
10. Any GI pathology or surgery or intractable vomiting likely to significantly influence drug absorption.
11. Inability to swallow the trial medication whole (e.g. due to dysphagia). 12. Known or suspected acute or chronic alcoholism, delirium tremens, or toxic psychosis.
13. Signs and symptoms that may be related to opioid withdrawal. 14. Use of prohibited medication or treatments as defined in the list of not allowed medication or treatments.
15. For women: Pregnancy or breast-feeding. Women of childbearing potential unable or unwilling to undergo pregnancy tests and practice acceptable contraceptive measures. Acceptable methods for women are hormonal contraceptives, surgical intervention (e.g. bilateral tubal occlusion), intrauterine device, intrauterine hormone-releasing system, double-barrier methods and true sexual abstinence (i.e. when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. For men: Men unable or unwilling to practice acceptable contraceptive measures. Acceptable methods for men are surgical intervention (e.g. vasectomy), true sexual abstinence and acceptable contraception (as described above) of the female partner.
16. Previous enrolment in this trial or participation in any other drug investigational trial within the past 30 days (or five half-lives of IMP whichever is longer) prior to Visit 1 (except one re-screening in this trial).
17. Previous treatment in a clinical trial with Naloxone HCl PR Tablets (except one re-screening in this trial).
18. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities.
19. Employees of the investigator or trial centre, with direct involvement in the proposed trial or other studies under the direction of that investigator or trial centre, as well as family members of the employees or the investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: Placebo
|
Placebo
|
|
Experimental: Naloxone 24 mg
|
oral administration
|
|
Experimental: Naloxone 48 mg
|
oral administration
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Proportion of overall CSBM Responders.
Time Frame: 12 weeks
|
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.
|
12 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0217/DEV
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Opioid-Induced Constipation
-
Sisli Hamidiye Etfal Training and Research HospitalCompletedConstipation, Opioid-InducedTurkey (Türkiye)
-
Professor Monique A. H. SteegersViatris Inc.RecruitingCancer | Opioid Induced Constipation (OIC)Netherlands
-
Amsterdam UMC, location VUmcRadboud University Medical Center; University Medical Center Groningen; Erasmus... and other collaboratorsRecruitingConstipation, Opioid-InducedNetherlands
-
Kyowa Kirin Pharmaceutical Development LtdTerminatedOpioid Induced ConstipationNetherlands, United Kingdom
-
Valinor Pharma LLCActive, not recruiting
-
St. John Health System, MichiganUnknownOpioid-induced ConstipationUnited States
-
Kyowa Kirin Pharmaceutical Development LtdCompletedOpioid Induced ConstipationUnited Kingdom, Norway, Sweden, Germany
-
Bausch Health Americas, Inc.Completed
-
AstraZenecaQuintilesIMS, Inc.CompletedOpioid Induced ConstipationUnited States
-
Mundipharma Research GmbH & Co KGCompleted
Clinical Trials on Placebo Oral Tablet
-
Fulcrum TherapeuticsCompletedFacioscapulohumeral Muscular Dystrophy (FSHD)United States, Canada, France, Spain
-
EicOsis Human Health Inc.CompletedHealthy SubjectsNew Zealand
-
Fulcrum TherapeuticsTerminated
-
EicOsis Human Health Inc.CompletedHealthy AdultsUnited States
-
Harmony Biosciences Management, Inc.CompletedMyotonic Dystrophy 1 | Excessive Daytime SleepinessUnited States, Canada
-
Syntrix Biosystems, Inc.National Institute on Drug Abuse (NIDA); DF/Net ResearchCompletedDiabetic Neuropathies | Neuropathic Pain | Pain, ChronicUnited States
-
The Mind Research NetworkTerminatedSmoking Cessation | Tobacco Use DisorderUnited States
-
EicOsis Human Health Inc.Congressionally Directed Medical Research ProgramsRecruitingDegenerative Disc Disease | Neuropathic Pain | Spinal Stenosis | Spinal Cord Injuries | SpondylosisUnited States
-
Cara Therapeutics, Inc.CompletedChronic Kidney Diseases | PruritusUnited States
-
Sunshine Lake Pharma Co., Ltd.CompletedChronic Hepatitis CChina