Naloxone HCl PR Tablets in Patients With Opioid Induced Constipation

Phase 3

• Conditions: Opioid-Induced Constipation
• Interventions: Drug: Naloxone HCl PR tablets; Drug: Placebo Oral Tablet

• Registration Number: NCT03687268
• Lead Sponsor: Develco Pharma Schweiz AG

Brief Summary

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):

Detailed Description

Not available

Study Timeline

• Study Start: 2017-07-31
• Status Verified: 2018-09
• Study First Submitted: 2018-09-26
• Study First Submitted QC: 2018-09-26
• Study First Posted: 2018-09-27
• Last Update Submitted: 2018-09-27
• Last Update Posted: 2018-09-28
• Primary Completion: 2019-11
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1500

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,

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.

  8. Any GI pathology or surgery or intractable vomiting likely to significantly influence drug absorption.

  9. 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.

  10. 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.

  11. 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.

  12. 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).

  13. Previous treatment in a clinical trial with Naloxone HCl PR Tablets (except one re-screening in this trial).

  14. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities.

  15. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Naloxone 48 mg	Naloxone HCl PR tablets	-
Naloxone 24 mg	Naloxone HCl PR tablets	-
Placebo	Placebo Oral Tablet	-

Primary Outcome Measures

Name	Time	Method
Proportion of overall CSBM Responders.	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.

Trial Locations

Locations (104)

Amadora; 🇵🇹 Amadora, Portugal

Žilina; 🇸🇰 Žilina, Slovakia

Novi Sad; 🇷🇸 Novi Sad, Serbia

Sombor; 🇷🇸 Sombor, Serbia

Banská Bystrica; 🇸🇰 Banská Bystrica, Slovakia

Bojnice; 🇸🇰 Bojnice, Slovakia

Bratislava; 🇸🇰 Bratislava, Slovakia

Uherské Hradiště; 🇨🇿 Uherské Hradiště, Czechia

Bydgoszcz; 🇵🇱 Bydgoszcz, Poland

Most; 🇨🇿 Most, Czechia

Ostrava; 🇨🇿 Ostrava, Czechia

Fellbach; 🇩🇪 Fellbach, Germany

Bielsko-Biala; 🇵🇱 Bielsko-Biala, Poland

Tarnow; 🇵🇱 Tarnów, Poland

Wloclawek; 🇵🇱 Włocławek, Poland

Subotica; 🇷🇸 Subotica, Serbia

Zrenjanin; 🇷🇸 Zrenjanin, Serbia

Belfast; 🇬🇧 Belfast, United Kingdom

Berlin; 🇩🇪 Berlin, Germany

Zlín; 🇨🇿 Zlín, Czechia

Rzeszow; 🇵🇱 Rzeszów, Poland

Aveiro; 🇵🇹 Aveiro, Portugal

Bad Pyrmont; 🇩🇪 Bad Pyrmont, Germany

Braga; 🇵🇹 Braga, Portugal

Gdansk; 🇵🇱 Gdańsk, Poland

Krakow; 🇵🇱 Kraków, Poland

Sokolov; 🇨🇿 Sokolov, Czechia

Bad Honnef; 🇩🇪 Bad Honnef, Germany

Plzeň; 🇨🇿 Plzen, Czechia

Praha 10; 🇨🇿 Praha 10, Czechia

Belgrade; 🇷🇸 Belgrade, Serbia

Katowice; 🇵🇱 Katowice, Poland

Lodz; 🇵🇱 Łódź, Poland

Covilhã; 🇵🇹 Covilhã, Portugal

Guimarães; 🇵🇹 Guimarães, Portugal

Bonn; 🇩🇪 Bonn, Germany

Corby; 🇬🇧 Corby, United Kingdom

Manises; 🇪🇸 Manises, Spain

Clevedon; 🇬🇧 Clevedon, United Kingdom

Santiago de Compostela; 🇪🇸 Santiago De Compostela, Spain

Aberdeen; 🇬🇧 Aberdeen, United Kingdom

Sremska Kamenica; 🇷🇸 Sremska Kamenica, Serbia

Chesterfield; 🇬🇧 Chesterfield, United Kingdom

Guildford; 🇬🇧 Guildford, United Kingdom

Middlesborough; 🇬🇧 Middlesbrough, United Kingdom

Addlestone; 🇬🇧 Addlestone, United Kingdom

Rimavská Sobota; 🇸🇰 Rimavská Sobota, Slovakia

Durham; 🇬🇧 Durham, United Kingdom

Margate; 🇬🇧 Margate, United Kingdom

Torrejón de Ardoz; 🇪🇸 Torrejón De Ardoz, Spain

Northwood; 🇬🇧 Northwood, United Kingdom

Leicester; 🇬🇧 Leicester, United Kingdom

Penzance; 🇬🇧 Penzance, United Kingdom

Romford; 🇬🇧 Romford, United Kingdom

Sidcup; 🇬🇧 Sidcup, United Kingdom

Plymouth; 🇬🇧 Plymouth, United Kingdom

Wellingborough; 🇬🇧 Wellingborough, United Kingdom

Thornton-Cleveleys; 🇬🇧 Thornton-Cleveleys, United Kingdom

Leiria; 🇵🇹 Leiria, Portugal

Barcelona; 🇪🇸 Barcelona, Spain

Granada; 🇪🇸 Granada, Spain

Salford; 🇬🇧 Salford, United Kingdom

Wokingham; 🇬🇧 Wokingham, United Kingdom

Hamburg; 🇩🇪 Hamburg, Germany

Palma; 🇪🇸 Palma De Mallorca, Spain

Sunderland; 🇬🇧 Sunderland, United Kingdom

Göppingen; 🇩🇪 Göppingen, Germany

Jahnsdorf; 🇩🇪 Jahnsdorf, Germany

Kevelaer; 🇩🇪 Kevelaer, Germany

Würzburg; 🇩🇪 Würzburg, Germany

Hradec Králové; 🇨🇿 Hradec Králové, Czechia

Liberec; 🇨🇿 Liberec, Czechia

Sevlievo; 🇧🇬 Sevlievo, Bulgaria

Plovdiv; 🇧🇬 Plovdiv, Bulgaria

Sofia; 🇧🇬 Sofia, Bulgaria

Choceň; 🇨🇿 Choceň, Czechia

Veliko Tarnovo; 🇧🇬 Veliko Tarnovo, Bulgaria

Znojmo; 🇨🇿 Znojmo, Czechia

České Budějovice; 🇨🇿 České Budějovice, Czechia

Eichstätt; 🇩🇪 Eichstätt, Germany

Böhlen; 🇩🇪 Böhlen, Germany

Münster; 🇩🇪 Münster, Germany

Marburg; 🇩🇪 Marburg, Germany

Stadtroda; 🇩🇪 Stadtroda, Germany

Bialystok; 🇵🇱 Białystok, Poland

Ostrowiec Swietokrzyski; 🇵🇱 Ostrowiec Świętokrzyski, Poland

Warszawa; 🇵🇱 Warszawa, Poland

Tychy; 🇵🇱 Tychy, Poland

Kragujevac; 🇷🇸 Kragujevac, Serbia

Setúbal; 🇵🇹 Setúbal, Portugal

Matosinhos; 🇵🇹 Matosinhos, Portugal

Nis; 🇷🇸 Niš, Serbia

Vrbas; 🇷🇸 Vrbas, Serbia

Dolný Kubín; 🇸🇰 Dolný Kubín, Slovakia

Prešov; 🇸🇰 Prešov, Slovakia

Košice; 🇸🇰 Košice, Slovakia

Cockermouth; 🇬🇧 Cockermouth, United Kingdom

Dunfermline; 🇬🇧 Dunfermline, United Kingdom

Fowey; 🇬🇧 Fowey, United Kingdom

Kenilworth; 🇬🇧 Kenilworth, United Kingdom

Macclesfield; 🇬🇧 Macclesfield, United Kingdom

Newcastle-Upon-Tyne; 🇬🇧 Newcastle Upon Tyne, United Kingdom

Middlesex; 🇬🇧 Middlesex, United Kingdom

Madrid; 🇪🇸 Madrid, Spain