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: 14.1Level: LLTClassification code 10071128Term: Opioid induced constipationSystem Organ Class: 100000004856; Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

• Registration Number: EUCTR2012-003218-14-ES
• Lead Sponsor: Develco Pharma Schweiz AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-22
• Last Update Posted: 27 October 2014

Recruitment & Eligibility

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

Inclusion Criteria

1. Male and female subjects equal or older than18 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 for at least the last 4 weeks before Visit 1.
3. Requirement of laxatives to have bowel movements (BMs), or having less than 3 BMs per week when not taking laxatives, respectively, for at least the last 4 weeks before Visit 1.
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 compliance 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) and 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, or neural blockade 2 weeks prior to Visit 1 and/or anticipated and/or scheduled during the course of the trial.
8. Evidence of impaired hepatic function (total bilirubin,aspartate aminotransferase [AST], alanine transaminase [ALT], gamma glutamyltransferase [GGT], or alkaline phosphatase [AP] >3 times the upper limit of normal).
9. Evidence of impaired renal function (creatinine clearance [CRCL] <90 mL/min).
10. Known or suspected significant circulatory disturbance, hypotension, or circulatory shock.
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 urinary retention.
16. Known or suspected CNS depression (signs/symptoms: decreased vital signs, impaired thinking and perception, slurred speech, slowed reflexes, fatigue, decreased consciousness), coma, or convulsive disorder.
17. Known or suspected elevation of intracranial pressure.
18. Known or suspected acute alcoholism, delirium tremens, or toxic psychosis.
19. History of drug addiction or drug seeking behaviour, positive test of illicit drugs at screening.
20. Concomitant treatment with other laxatives (except stable therapy with fibre supplementation or bulking agents), 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. Substantial changes in concomitant therapies with other compounds that can influence pain response such as nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, paracetamol, corticosteroids, anti-depressants, anxiolytics, neuroleptics or non-drug treatments such as physical measures or acupuncture.
21. Pregnancy or breast-feeding. Women of childbearing potential unable or unwilling to undergo pregnancy tests and practi

Study & Design

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