Clinical study to investigate the efficacy, safety and tolerability of Naloxone in patients with opioid induced constipation.

• Conditions: Opioid-induced bowel dysfunction (OBD) involves not only constipation, but also a constellation of symptoms including incomplete evacuation, bloating, abdominal distension, and increased gastric reflux.Constipation is an almost inevitable consequence of opioid use in malignant and non-malignant disease states, and one of the side effects of opioids to which few patients develop tolerance.; MedDRA version: 16.1Level: LLTClassification code 10071128Term: Opioid induced constipationSystem Organ Class: 100000004856; Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

• Registration Number: EUCTR2012-004311-31-GB
• Lead Sponsor: Develco Pharma Schweiz AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01-29
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 306

Inclusion Criteria

1. Male and female subjects =18 years of age.
2. Subjects with a documented history of constipation induced or worsened by their oral or sublingual WHO step-II or step-III opioid medication.
3. Requirement of laxatives to have bowel movements (BMs), or having less than 3 BMs per week when not taking laxatives, respectively.
4. Subjects with documented history of chronic severe non-malignant pain that requires around-the-clock opioid therapy and likely to benefit from WHO step-III opioid therapy for the duration of the trial.
5. Subjects with predominantly non-neuropathic pain, as determined by a DN4 Neuropathic Pain Diagnostic Questionnaire score < 4 .
6. Subjects willing and able (e.g. mental and physical condition) to participate in all aspects of the trial, including use of medication, completion of subjective evaluations, attending scheduled visits, completing telephone interviews, and compliant with protocol requirements as evidenced by providing signed written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 106

Exclusion Criteria

1. Subjects with any situation in which opioids are contra-indicated, severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive pulmonary disease, cor pulmonale, severe bronchial asthma, paralytic ileus.
2. Hypersensitivity or intolerance to any active substance, i.e. oxycodone, hydromorphone, morphine, naloxone, bisacodyl, or any of the excipients of the trial medication, e.g. subjects with hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
3. Intake of naloxone or naltrexone or injection of methylnaltrexone within the past 30 days prior to Visit 1.
4. Subjects unwilling to discontinue pre-trial laxative medication (except fibre supplementation or bulking agents at a stable dose) & take trial specific laxative medication.
5. Any gastrointestinal pathology or surgery or intractable vomiting likely to significantly influence drug absorption.
6. Inability to swallow the trial drugs whole (e.g. due to dysphagia).
7. Surgery within 1 month, radiotherapy or neural blockade 2 weeks prior to Visit 1 &/or anticipated &/or scheduled during the course of the trial.
8. Evidence of impaired hepatic function (total bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyltransferase [GGT], or alkaline phosphatase [AP] >3 times the upper limit of normal).
9. Evidence of moderate or severe renal function impairment (creatinine clearance [CRCL] <60 mL/min).
10. Known or suspected significant hypotension, shock or severe cardiovascular disease.
11. Known or suspected clinically relevant endocrine disorder, such as myxoedema, not adequately treated hypothyroidism or adrenocortical insufficiency (e.g. Addison's disease)
12. Known or suspected clinically significant bowel disease (e.g. paralytic ileus, significant impairment of bowel motility severe enough to potentially result in ileus, obstructive or inflammatory bowel disease, anal fissures or ulcerative proctitis).
13. Subjects with a confirmed diagnosis of ongoing irritable bowel syndrome.
14. Known or suspected acute or chronic pancreatitis or clinically relevant biliary tract disease.
15. Known or suspected significant prostatic hypertrophy or urethral stricture severe enough to potentially result in acute urinary retention.
16. Known or suspected CNS depression (signs/symptoms: decreased vital signs, impaired thinking & perception, slurred speech, slowed reflexes, fatigue, decreased consciousness), coma, or convulsive disorder.
17. Known or suspected cranio-cerebral trauma or elevation of intracranial pressure.
18. Known or suspected acute alcoholism, delirium tremens, or toxic psychosis.
19. Known or suspected severe psychiatric disorders.
20. History of drug addiction or drug seeking behaviour, positive test of illicit drugs at screening.
21. Concomitant treatment with other naloxone preparations (apart from IMP), naltrexone or methylnaltrexone preparations, other laxatives (except stable therapy with fibre supplementation or bulking agents), other medicines that can cause constipation or influence bowel motility, other opioid analgesics (including codeine-containing compounds), non-opioid analgesics taken on an as-needed basis, monoamine oxidase (MAO) inhibitors or any form of neural blockade or radiotherapy. Substantial changes in concomitant therapies with other compounds that can influence pain response such as nonsteroidal anti-inflammatory drug

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified