Clinical trial NCT03687268: Naloxone HCl PR Tablets in Patients With Opioid Induced Constipation
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Opioid-Induced Constipation
Lead sponsor: Develco Pharma Schweiz AG
Sponsor class: INDUSTRY
First posted: 2018-09-27
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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):


Eligibility 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,

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.

Primary outcomes:
measure: Proportion of overall CSBM Responders.
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Plovdiv
city: Sevlievo
country: Bulgaria
facility: Sevlievo
city: Sofia
country: Bulgaria
facility: Sofia
city: Veliko Tarnovo
country: Bulgaria
facility: Veliko Tarnovo
city: Choceň
country: Czechia
facility: Choceň
city: Hradec Králové
country: Czechia
facility: Hradec Králové
city: Liberec
country: Czechia
facility: Liberec
city: Most
country: Czechia
facility: Most
city: Ostrava
country: Czechia
facility: Ostrava
city: Plzen
country: Czechia
facility: Plzeň
city: Praha 10
country: Czechia
facility: Praha 10
city: Sokolov
country: Czechia
facility: Sokolov
city: Uherské Hradiště
country: Czechia
facility: Uherské Hradiště
city: Zlín
country: Czechia
facility: Zlín
city: Znojmo
country: Czechia
facility: Znojmo
city: České Budějovice
country: Czechia
facility: České Budějovice
city: Bad Honnef
country: Germany
facility: Bad Honnef
city: Bad Pyrmont
country: Germany
facility: Bad Pyrmont
city: Berlin
country: Germany
facility: Berlin
city: Bonn
country: Germany
facility: Bonn
city: Böhlen
country: Germany
facility: Böhlen
city: Eichstätt
country: Germany
facility: Eichstätt
city: Fellbach
country: Germany
facility: Fellbach
city: Göppingen
country: Germany
facility: Göppingen
city: Hamburg
country: Germany
facility: Hamburg
city: Jahnsdorf
country: Germany
facility: Jahnsdorf
city: Kevelaer
country: Germany
facility: Kevelaer
city: Marburg
country: Germany
facility: Marburg
city: Münster
country: Germany
facility: Münster
city: Stadtroda
country: Germany
facility: Stadtroda
city: Würzburg
country: Germany
facility: Würzburg
city: Białystok
country: Poland
facility: Bialystok
city: Bielsko-Biala
country: Poland
facility: Bielsko-Biala
city: Bydgoszcz
country: Poland
facility: Bydgoszcz
city: Gdańsk
country: Poland
facility: Gdansk
city: Katowice
country: Poland
facility: Katowice
city: Kraków
country: Poland
facility: Krakow
city: Ostrowiec Świętokrzyski
country: Poland
facility: Ostrowiec Swietokrzyski
city: Rzeszów
country: Poland
facility: Rzeszow
city: Tarnów
country: Poland
facility: Tarnow
city: Tychy
country: Poland
facility: Tychy
city: Warszawa
country: Poland
facility: Warszawa
city: Włocławek
country: Poland
facility: Wloclawek
city: Łódź
country: Poland
facility: Lodz
city: Amadora
country: Portugal
facility: Amadora
city: Aveiro
country: Portugal
facility: Aveiro
city: Braga
country: Portugal
facility: Braga
city: Covilhã
country: Portugal
facility: Covilhã
city: Guimarães
country: Portugal
facility: Guimarães
city: Leiria
country: Portugal
facility: Leiria
city: Matosinhos
country: Portugal
facility: Matosinhos
city: Setúbal
country: Portugal
facility: Setúbal
city: Belgrade
country: Serbia
facility: Belgrade
city: Kragujevac
country: Serbia
facility: Kragujevac
city: Niš
country: Serbia
facility: Nis
city: Novi Sad
country: Serbia
facility: Novi Sad
city: Sombor
country: Serbia
facility: Sombor
city: Sremska Kamenica
country: Serbia
facility: Sremska Kamenica
city: Subotica
country: Serbia
facility: Subotica
city: Vrbas
country: Serbia
facility: Vrbas
city: Zrenjanin
country: Serbia
facility: Zrenjanin
city: Banská Bystrica
country: Slovakia
facility: Banská Bystrica
city: Bojnice
country: Slovakia
facility: Bojnice
city: Bratislava
country: Slovakia
facility: Bratislava
city: Dolný Kubín
country: Slovakia
facility: Dolný Kubín
city: Košice
country: Slovakia
facility: Košice
city: Prešov
country: Slovakia
facility: Prešov
city: Rimavská Sobota
country: Slovakia
facility: Rimavská Sobota
city: Žilina
country: Slovakia
facility: Žilina
city: Barcelona
country: Spain
facility: Barcelona
city: Granada
country: Spain
facility: Granada
city: Madrid
country: Spain
facility: Madrid
city: Manises
country: Spain
facility: Manises
city: Palma De Mallorca
country: Spain
facility: Palma
city: Santiago De Compostela
country: Spain
facility: Santiago de Compostela
city: Torrejón De Ardoz
country: Spain
facility: Torrejón de Ardoz
city: Aberdeen
country: United Kingdom
facility: Aberdeen
city: Addlestone
country: United Kingdom
facility: Addlestone
city: Belfast
country: United Kingdom
facility: Belfast
city: Chesterfield
country: United Kingdom
facility: Chesterfield
city: Clevedon
country: United Kingdom
facility: Clevedon
city: Cockermouth
country: United Kingdom
facility: Cockermouth
city: Corby
country: United Kingdom
facility: Corby
city: Dunfermline
country: United Kingdom
facility: Dunfermline
city: Durham
country: United Kingdom
facility: Durham
city: Fowey
country: United Kingdom
facility: Fowey
city: Guildford
country: United Kingdom
facility: Guildford
city: Kenilworth
country: United Kingdom
facility: Kenilworth
city: Leicester
country: United Kingdom
facility: Leicester
city: Macclesfield
country: United Kingdom
facility: Macclesfield
city: Margate
country: United Kingdom
facility: Margate
city: Middlesbrough
country: United Kingdom
facility: Middlesborough
city: Middlesex
country: United Kingdom
facility: Middlesex
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle-Upon-Tyne
city: Northwood
country: United Kingdom
facility: Northwood
city: Penzance
country: United Kingdom
facility: Penzance
city: Plymouth
country: United Kingdom
facility: Plymouth
city: Romford
country: United Kingdom
facility: Romford
city: Salford
country: United Kingdom
facility: Salford
city: Sidcup
country: United Kingdom
facility: Sidcup
city: Sunderland
country: United Kingdom
facility: Sunderland
city: Thornton-Cleveleys
country: United Kingdom
facility: Thornton-Cleveleys
city: Wellingborough
country: United Kingdom
facility: Wellingborough
city: Wokingham
country: United Kingdom
facility: Wokingham
Study officials:
References: