Naloxone SR Capsules in Patients With Opioid Induced Constipation

Condition(s) targeted: Chronic Non-cancer Pain; Opioid Induced Constipation

Intervention: Naloxone SR 5 mg capsules (Drug); Placebo (Drug); Naloxone SR 10 mg capsules (Drug); Naloxone SR 20mg capsules (Drug); Naloxone SR 2.5 mg capsules (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: S.L.A. Pharma AG

Overall contact:
Stephen Jones, MBBS, Phone: 07787555881, Email: sjones@synapsemr.com

For many patients taking opioids for pain relief one of the most distressing side effects is constipation. Naloxone is effective in the reversal of the effects of opioids and is used following opioid overdose. If naloxone is given by mouth it would relieve the effects of constipation but as it goes into the blood stream very quickly, it would also reverse the effects of the opioid and therefore stop the pain relief. The aim of this study is to examine a slow release formulation of naloxone to see if is can reduce constipation without reducing the pain relieving effects of the opioid.

Official title: A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study Evaluating the Safety, Tolerability and Efficacy of Naloxone SR Capsules in Subjects With Constipation Due to Opioids, Taken for Persistent Non-Cancer Pain

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: To assess the safety and tolerability of multiple doses of Naloxone SR capsules in subjects taking opioid analgesics

Detailed description: Naloxone has been used for many years as an IV or IM injection for the reversal of opioid effects (following opioid overdose) and has been evaluated as an oral formulation to manage opioid-induced constipation. Immediate release oral naloxone preparations have however led to reversal of opioid effects and withdrawal. This has initiated the development of prolonged (slow release) naloxone preparations which prevent the systemic levels of naloxone reaching levels where the central opioid effects may be reversed. Naloxone has a high first pass metabolism (98%) and short half life (~1hr).

The objectives of this trial are to identify the optimum dosage regime of Naloxone SR capsules based on tolerability level, to improve spontaneous bowel movement frequency, and relieve GI symptoms, in patients suffering with opioid induced constipation.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- All subjects must give written informed consent

- Male or female subjects greater than 18 years of age

- Taking opioid full agonist therapy(oral or transdermal) for persistent non-cancer

pain, for at least 4 weeks prior to baseline visit

- Subjects with at least a 3 week history of OIC prior to baseline; where bowel

dysfunction is predominantly due to opioids and started following commencement of opioid therapy

- Subjects with <3 SBMs a week and experiencing one or more bowel symptoms (incomplete

evacuation, straining, hard/small pellets) for 25% or more of bowel movements during the screening period

- Subjects must be willing to discontinue all current laxative (constipation) therapy.

Bisacodyl will be provided and taken as required

Exclusion Criteria:

- Women of childbearing potential, unless surgically sterile or using adequate

contraception (either IUD, oral or depot contraceptive, or barrier plus spermicide). Women using oral contraception must have started using it at least 2 months prior to enrolment

- Women who are pregnant or breastfeeding

- Symptoms suggestive of non-opioid related bowel dysfunction (e. g. IBS - intermittent

constipation or diarrhoea) or have diarrhoea or loose stools in the 4 weeks prior to baseline

- History of chronic constipation prior to commencing opioid therapy

- Gastrointestinal disorders known to affect bowel transit, or contribute to bowel

dysfunction (other than OIC)

- Chronic faecal incontinence

- Subjects who have a colostomy, ileostomy, or colectomy with ileorectal anastomosis

- Subjects with a history of neoplastic disease within 5 years (except for basal cell

carcinoma or non-metastatic squamous cell carcinoma of the skin)

- Subjects taking opioids for the management of drug addiction Subjects who do not meet

any of the following criteria regarding baseline medications. Analgesia (including opioids and NSAIDs) should be stable throughout the trial.

- Any baseline analgesia must have been administered at a stable dose for a

minimum of 4 weeks. If non-opioid analgesia recently discontinued, must have stopped at least 4 weeks prior to baseline

- Laxatives (outside that allowed by the protocol) are not permitted; these agents

must have been discontinued at the screening visit.

- Use of drugs known to affect gut transit time (other than opioids) are not

permitted (see Section 6. 9 for exceptions)

- Use of mixed agonist/antagonist, or partial agonist opioids are not permitted

(e. g. buprenorphine, pentazocine, cyclazocine, nalbuphine, nalorphine)

- Experimental agents must have been discontinued at least 8 weeks prior to

screening, or for a period equivalent to 5 half-lives (t½) of the agent (whichever is longer)

- Subjects with a history of clinically significant and/or persistent disorder

that, in the investigators opinion, may affect the clinical trial assessments

- Subjects with any laboratory tests considered clinically significant at

screening.

- Subjects not ambulatory i. e. bedridden or require use of a commode

- Subjects who will be unavailable for the duration of the trial, likely to be

non-compliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason

Stephen Jones, MBBS, Phone: 07787555881, Email: sjones@synapsemr.com

Schmerzzentrum Berlin, Berlin 10435, Germany; Recruiting
Jan-Peter Jansen, Phone: 030 4434 1901, Email: jansen@schmerzzentrum-berline.de
K Hannig, Phone: 030 4434 1901
Jan-Peter Jansen, Principal Investigator

Schmerzzentrum Frankfurt, Frankfurt 60311, Germany; Recruiting
Hubert Miles, Phone: 069 299 8800, Email: schmerzzentrum@floeter.org
Hubert Miles, Principal Investigator

Gemeinschaftspraxis Tamm-Albert-Schroter-Uhmann, Hannover 30167, Germany; Withdrawn

Gemeinschaftspraxis Loewenstein-Hesselbarth, Mainz 55116, Germany; Recruiting
Oliver Loewenstein, Phone: 6131 6693401, Email: studien@praxis-loewenstein-hesselbarth.de
S Hesselbarth, Phone: 6131 6693401, Email: studien@praxis-loewenstein-hesselbarth.de
Oliver Loewenstein, Principal Investigator

Regionales Schmerzzentrum Wuppertal, Wuppertal 42105, Germany; Recruiting
Adrian Stoenescu, Phone: 0049 (0202) 28 32 800, Email: info@schmerzcenter-wuppertal.de
Adrian Stoenescu, Principal Investigator

St Jame's Hospital Leeds, Leeds LS9 7TF, United Kingdom; Recruiting
Helen Radford, Phone: 0113 2063129, Email: heleneradford@msn.com
Tracey Crowther, Phone: 0113 2063129
Karen Simson, Principal Investigator

Norfolk & Norwich Hospital, Norwich NR4 7UY, United Kingdom; Recruiting
Mark Sanders, Email: mark.sanders@nnuh.nhs.uk
Claire Brennan, Phone: 01603 597276, Email: Claire.brennan@nnuh.nhs.uk
Mark Sanders, Principal Investigator

Northern General Hospital, Sheffield S5 7AU, United Kingdom; Withdrawn

Department of Pain Management, York Hospital, York LS14 6UH, United Kingdom; Completed

Starting date: October 2009
Last updated: November 2, 2011