E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Opioid Induced Constipation |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of multiple doses of Naloxone SR capsules in subjects taking opioid analgesics. |
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E.2.2 | Secondary objectives of the trial |
1) To determine whether Naloxone SR capsules produce opioid withdrawal symptoms. 2) To determine the ability of Naloxone SR capsules to improve the number of weekly spontaneous bowel movements. 3) To determine the effect of Naloxone SR capsules on quality of life. 4) To determine the effect of Naloxone SR capsules on bowel symptoms (straining, stool consistency, incomplete evacuation)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· All subjects must give written informed consent; · Male or female subjects, ≥18 years of age; · Taking full opioid agonist oral therapy for persistent non-cancer pain, for at least 4 weeks prior to baseline visit (the number of patients taking opioids via transdermal patch will be limited to no more than three in any one cohort) · 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 if required. |
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E.4 | Principal 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, it 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) is not permitted (see Section 6.9 for exceptions); · Use of mixed agonist/antagonist, or partial agonist opioids is 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
· The incidence and severity of treatment-emergent adverse events (TEAEs) on single dosing (i.e. through to week 3). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit last subject in Cohort 4. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |