Naloxone SR Capsules in Patients With Opioid Induced Constipation
Condition: Chronic Pain; Opioid Induced Constipation
MeSH terms: Chronic Pain; Constipation; Opioid-Induced Constipation
Intervention: Naloxone SR 5 mg capsules; Placebo; Naloxone SR 10 mg capsules; Naloxone SR 20mg capsules; Naloxone SR 2.5 mg capsules
Intervention MeSH terms: Naloxone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pain; opioid; constipation; Subjects taking opioids for chronic non-cancer pain, who; experience symptoms of opioid induced constipation

Summary:

      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.
    

Eligibility 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