Naloxone HCl PR Tablets in Patients With Opioid Induced Constipation

NCT03687268 | Unknown Phase 3 FDA Drug

• 1 other identifier: 0217/DEV
• Study Type: interventional
• Target: 1,500
• Locations: 9 countries
• Sites: 104

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):

Conditions

Opioid-Induced Constipation

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo Oral Tablet

Naloxone 24 mg

EXPERIMENTAL

Drug: Naloxone HCl PR tablets

Naloxone 48 mg

EXPERIMENTAL

Drug: Naloxone HCl PR tablets

Interventions

Naloxone HCl PR tablets DRUG

oral administration

Naloxone 24 mg; Naloxone 48 mg

Placebo Oral Tablet DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• \. 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.
• \. 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.
• \. Known or suspected reason for constipation other than OIC (e.g. idiopathic, neurological, endocrine, or metabolic).
• \. 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).
• \. 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.
• \. Any form of acute temporary or permanent GI ostomy, such as ileostomy or colostomy.
• \. 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.
• \. Any GI pathology or surgery or intractable vomiting likely to significantly influence drug absorption.
• \. 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.
• \. 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.
• \. 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.
• \. 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).
• \. Previous treatment in a clinical trial with Naloxone HCl PR Tablets (except one re-screening in this trial).
• \. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities.
• \. 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.

Sponsors & Collaborators

• Develco Pharma Schweiz AG: lead

Study Sites (104)

Plovdiv

Plovdiv, Bulgaria

RECRUITING

Sevlievo

Sevlievo, Bulgaria

RECRUITING

Sofia

Sofia, Bulgaria

RECRUITING

Veliko Tarnovo

Veliko Tarnovo, Bulgaria

RECRUITING

Choceň

Choceň, Czechia

RECRUITING

České Budějovice

České Budějovice, Czechia

RECRUITING

Hradec Králové

Hradec Králové, Czechia

RECRUITING

Liberec

Liberec, Czechia

RECRUITING

Most

Most, Czechia

RECRUITING

Ostrava

Ostrava, Czechia

RECRUITING

Plzeň

Pilsen, Czechia

RECRUITING

Praha 10

Prague, Czechia

RECRUITING

Sokolov

Sokolov, Czechia

RECRUITING

Uherské Hradiště

Uherské Hradiště, Czechia

RECRUITING

Zlín

Zlín, Czechia

RECRUITING

Znojmo

Znojmo, Czechia

RECRUITING

Bad Honnef

Bad Honnef, Germany

RECRUITING

Bad Pyrmont

Bad Pyrmont, Germany

RECRUITING

Berlin

Berlin, Germany

RECRUITING

Bonn

Bonn, Germany

RECRUITING

Böhlen

Böhlen, Germany

RECRUITING

Eichstätt

Eichstätt, Germany

RECRUITING

Fellbach

Fellbach, Germany

RECRUITING

Göppingen

Göppingen, Germany

RECRUITING

Hamburg

Hamburg, Germany

RECRUITING

Jahnsdorf

Jahnsdorf, Germany

RECRUITING

Kevelaer

Kevelaer, Germany

RECRUITING

Marburg

Marburg, Germany

RECRUITING

Münster

Münster, Germany

RECRUITING

Stadtroda

Stadtroda, Germany

RECRUITING

Würzburg

Würzburg, Germany

RECRUITING

Bialystok

Bialystok, Poland

RECRUITING

Bielsko-Biala

Bielsko-Biala, Poland

RECRUITING

Bydgoszcz

Bydgoszcz, Poland

RECRUITING

Gdansk

Gdansk, Poland

RECRUITING

Katowice

Katowice, Poland

RECRUITING

Krakow

Krakow, Poland

RECRUITING

Lodz

Lodz, Poland

RECRUITING

Ostrowiec Swietokrzyski

Ostrowiec Świętokrzyski, Poland

RECRUITING

Rzeszow

Rzeszów, Poland

RECRUITING

Tarnow

Tarnów, Poland

RECRUITING

Tychy

Tychy, Poland

RECRUITING

Warszawa

Warsaw, Poland

RECRUITING

Wloclawek

Włocławek, Poland

RECRUITING

Amadora

Amadora, Portugal

RECRUITING

Aveiro

Aveiro, Portugal

RECRUITING

Braga

Braga, Portugal

RECRUITING

Covilhã

Covilha, Portugal

RECRUITING

Guimarães

Guimarães, Portugal

RECRUITING

Leiria

Leiria, Portugal

RECRUITING

Matosinhos

Matosinhos Municipality, Portugal

RECRUITING

Setúbal

Setúbal, Portugal

RECRUITING

Belgrade

Belgrade, Serbia

RECRUITING

Sremska Kamenica

Kamenitz, Serbia

RECRUITING

Kragujevac

Kragujevac, Serbia

RECRUITING

Nis

Niš, Serbia

RECRUITING

Novi Sad

Novi Sad, Serbia

RECRUITING

Sombor

Sombor, Serbia

RECRUITING

Subotica

Subotica, Serbia

RECRUITING

Vrbas

Vrbas, Serbia

RECRUITING

Zrenjanin

Zrenjanin, Serbia

RECRUITING

Banská Bystrica

Banská Bystrica, Slovakia

RECRUITING

Bojnice

Bojnice, Slovakia

RECRUITING

Bratislava

Bratislava, Slovakia

RECRUITING

Dolný Kubín

Dolný Kubín, Slovakia

RECRUITING

Košice

Košice, Slovakia

RECRUITING

Prešov

Prešov, Slovakia

RECRUITING

Rimavská Sobota

Rimavská Sobota, Slovakia

RECRUITING

Žilina

Žilina, Slovakia

RECRUITING

Barcelona

Barcelona, Spain

RECRUITING

Granada

Granada, Spain

RECRUITING

Madrid

Madrid, Spain

RECRUITING

Manises

Manises, Spain

RECRUITING

Palma

Palma de Mallorca, Spain

RECRUITING

Santiago de Compostela

Santiago de Compostela, Spain

RECRUITING

Torrejón de Ardoz

Torrejón de Ardoz, Spain

RECRUITING

Aberdeen

Aberdeen, United Kingdom

RECRUITING

Addlestone

Addlestone, United Kingdom

RECRUITING

Belfast

Belfast, United Kingdom

RECRUITING

Chesterfield

Chesterfield, United Kingdom

RECRUITING

Clevedon

Clevedon, United Kingdom

RECRUITING

Cockermouth

Cockermouth, United Kingdom

RECRUITING

Corby

Corby, United Kingdom

RECRUITING

Dunfermline

Dunfermline, United Kingdom

RECRUITING

Durham

Durham, United Kingdom

RECRUITING

Fowey

Fowey, United Kingdom

RECRUITING

Guildford

Guildford, United Kingdom

RECRUITING

Kenilworth

Kenilworth, United Kingdom

RECRUITING

Leicester

Leicester, United Kingdom

RECRUITING

Macclesfield

Macclesfield, United Kingdom

RECRUITING

Margate

Margate, United Kingdom

RECRUITING

Middlesborough

Middlesbrough, United Kingdom

RECRUITING

Middlesex

Middlesex, United Kingdom

RECRUITING

Newcastle-Upon-Tyne

Newcastle upon Tyne, United Kingdom

RECRUITING

Northwood

Northwood, United Kingdom

RECRUITING

Penzance

Penzance, United Kingdom

RECRUITING

Plymouth

Plymouth, United Kingdom

RECRUITING

Romford

Romford, United Kingdom

RECRUITING

Salford

Salford, United Kingdom

RECRUITING

Sidcup

Sidcup, United Kingdom

RECRUITING

Sunderland

Sunderland, United Kingdom

RECRUITING

Thornton-Cleveleys

Thornton-Cleveleys, United Kingdom

RECRUITING

Wellingborough

Wellingborough, United Kingdom

RECRUITING

Wokingham

Wokingham, United Kingdom

RECRUITING

MeSH Terms

Conditions

Opioid-Induced Constipation

Condition Hierarchy (Ancestors)

Constipation; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Central Study Contacts

Nils Burger, PhD

CONTACT

+41614255020; n.burger@develco.ch

Karin Schmid

CONTACT

+41614255020; k.schmid@develco.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: September 27, 2018
• Study Start: July 31, 2017
• Primary Completion: November 1, 2019
• Study Completion: December 1, 2019
• Last Updated: September 28, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

BU (4); SL (8); PT (8); CZ (12); DE (15); SE (9); PL (13); ES (7); GB (28)