Naloxone SR Capsules in Patients With Opioid Induced Constipation

November 7, 2013 updated by: S.L.A. Pharma AG

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 10435
        • Schmerzzentrum Berlin
      • Frankfurt, Germany, 60311
        • Schmerzzentrum Frankfurt
      • Hannover, Germany, 30167
        • Gemeinschaftspraxis Tamm-Albert-Schroter-Uhmann
      • Mainz, Germany, 55116
        • Gemeinschaftspraxis Loewenstein-Hesselbarth
      • Wuppertal, Germany, 42105
        • Regionales Schmerzzentrum Wuppertal
  • United Kingdom
      • Leeds, United Kingdom, LS9 7TF
        • St Jame's Hospital Leeds
      • Norwich, United Kingdom, NR4 7UY
        • Norfolk & Norwich Hospital
      • York, United Kingdom, LS14 6UH
        • Department of Pain Management, York Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Capsules with no active drug
Placebo capsules once daily for three weeks then twice daily for three weeks.
Drug: Placebo
Active Comparator: Naloxone SR 2.5 mg capsules
Naloxone SR 2.5 mg capsules once daily for three weeks then twice daily for three weeks.
Drug: Naloxone SR 2.5 mg capsules
Experimental: Naloxone SR 10mg capsules
Naloxone SR 10 mg capsules once daily for three weeks then twice daily for three weeks.
Drug: Naloxone SR 10 mg capsules
Experimental: Naloxone SR 20 mg capsules
Two Naloxone SR 10 mg capsules once daily for three weeks then twice daily for three weeks.
Drug: Naloxone SR 20mg capsules
Experimental: Naloxone SR 5mg capsules
Naloxone SR 5 mg capsules once daily for three weeks then twice daily for three weeks.
Drug: Naloxone SR 5 mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and Severity of Treatment Emergent Adverse Events on Single Dosing.
Time Frame: 3 weeks
Incidence and severity of treatment emergent adverse events on single dosing.
3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

S.L.A. Pharma AG

Investigators

  • Principal Investigator: Karen Simpson, MD, St James University Hospital, Leeds, UK

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

September 24, 2009

First Submitted That Met QC Criteria

September 24, 2009

First Posted (Estimate)

September 25, 2009

Study Record Updates

Last Update Posted (Estimate)

December 27, 2013

Last Update Submitted That Met QC Criteria

November 7, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NAL-OIC-01
  • 2009-009377-10 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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