Naloxone HCl PR Tablets in Patients With Opioid Induced Constipation

Opioid-Induced Constipation Clinical Trial

— Naxos  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03687268
• Other study ID #: 0217/DEV
• Status: Recruiting
• Phase: Phase 3
• Start date: July 31, 2017
• Est. completion date: December 2019

Study information

• Verified date: September 2018
• Source: Develco Pharma Schweiz AG
• Contact: Nils Burger, PhD
• Phone: +41614255020
• Email: n.burger[@]develco.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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):

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: December 2019
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Constipation
• Opioid-Induced Constipation

Intervention

Drug:
• Naloxone HCl PR tablets
oral administration
• Placebo Oral Tablet
Placebo

Locations

Country	Name	City	State
Bulgaria	Plovdiv	Plovdiv
Bulgaria	Sevlievo	Sevlievo
Bulgaria	Sofia	Sofia
Bulgaria	Veliko Tarnovo	Veliko Tarnovo
Czechia	Ceské Budejovice	Ceské Budejovice
Czechia	Chocen	Chocen
Czechia	Hradec Králové	Hradec Králové
Czechia	Liberec	Liberec
Czechia	Most	Most
Czechia	Ostrava	Ostrava
Czechia	Plzen	Plzen
Czechia	Praha 10	Praha 10
Czechia	Sokolov	Sokolov
Czechia	Uherské Hradište	Uherské Hradište
Czechia	Zlín	Zlín
Czechia	Znojmo	Znojmo
Germany	Bad Honnef	Bad Honnef
Germany	Bad Pyrmont	Bad Pyrmont
Germany	Berlin	Berlin
Germany	Böhlen	Böhlen
Germany	Bonn	Bonn
Germany	Eichstätt	Eichstätt
Germany	Fellbach	Fellbach
Germany	Göppingen	Göppingen
Germany	Hamburg	Hamburg
Germany	Jahnsdorf	Jahnsdorf
Germany	Kevelaer	Kevelaer
Germany	Marburg	Marburg
Germany	Münster	Münster
Germany	Stadtroda	Stadtroda
Germany	Würzburg	Würzburg
Poland	Bialystok	Bialystok
Poland	Bielsko-Biala	Bielsko-Biala
Poland	Bydgoszcz	Bydgoszcz
Poland	Gdansk	Gdansk
Poland	Katowice	Katowice
Poland	Krakow	Kraków
Poland	Lodz	Lódz
Poland	Ostrowiec Swietokrzyski	Ostrowiec Swietokrzyski
Poland	Rzeszow	Rzeszów
Poland	Tarnow	Tarnów
Poland	Tychy	Tychy
Poland	Warszawa	Warszawa
Poland	Wloclawek	Wloclawek
Portugal	Amadora	Amadora
Portugal	Aveiro	Aveiro
Portugal	Braga	Braga
Portugal	Covilhã	Covilhã
Portugal	Guimarães	Guimarães
Portugal	Leiria	Leiria
Portugal	Matosinhos	Matosinhos
Portugal	Setúbal	Setúbal
Serbia	Belgrade	Belgrade
Serbia	Kragujevac	Kragujevac
Serbia	Nis	Niš
Serbia	Novi Sad	Novi Sad
Serbia	Sombor	Sombor
Serbia	Sremska Kamenica	Sremska Kamenica
Serbia	Subotica	Subotica
Serbia	Vrbas	Vrbas
Serbia	Zrenjanin	Zrenjanin
Slovakia	Žilina	Žilina
Slovakia	Banská Bystrica	Banská Bystrica
Slovakia	Bojnice	Bojnice
Slovakia	Bratislava	Bratislava
Slovakia	Dolný Kubín	Dolný Kubín
Slovakia	Košice	Košice
Slovakia	Prešov	Prešov
Slovakia	Rimavská Sobota	Rimavská Sobota
Spain	Barcelona	Barcelona
Spain	Granada	Granada
Spain	Madrid	Madrid
Spain	Manises	Manises
Spain	Palma	Palma De Mallorca
Spain	Santiago de Compostela	Santiago De Compostela
Spain	Torrejón de Ardoz	Torrejón De Ardoz
United Kingdom	Aberdeen	Aberdeen
United Kingdom	Addlestone	Addlestone
United Kingdom	Belfast	Belfast
United Kingdom	Chesterfield	Chesterfield
United Kingdom	Clevedon	Clevedon
United Kingdom	Cockermouth	Cockermouth
United Kingdom	Corby	Corby
United Kingdom	Dunfermline	Dunfermline
United Kingdom	Durham	Durham
United Kingdom	Fowey	Fowey
United Kingdom	Guildford	Guildford
United Kingdom	Kenilworth	Kenilworth
United Kingdom	Leicester	Leicester
United Kingdom	Macclesfield	Macclesfield
United Kingdom	Margate	Margate
United Kingdom	Middlesborough	Middlesbrough
United Kingdom	Middlesex	Middlesex
United Kingdom	Newcastle-Upon-Tyne	Newcastle Upon Tyne
United Kingdom	Northwood	Northwood
United Kingdom	Penzance	Penzance
United Kingdom	Plymouth	Plymouth
United Kingdom	Romford	Romford
United Kingdom	Salford	Salford
United Kingdom	Sidcup	Sidcup
United Kingdom	Sunderland	Sunderland
United Kingdom	Thornton-Cleveleys	Thornton-Cleveleys
United Kingdom	Wellingborough	Wellingborough
United Kingdom	Wokingham	Wokingham

Sponsors (1)

Lead Sponsor	Collaborator
Develco Pharma Schweiz AG

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Germany,  Poland,  Portugal,  Serbia,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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