Naloxone SR Capsules in Patients With Opioid Induced Constipation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
S.L.A. Pharma AG
ClinicalTrials.gov Identifier:
NCT00984334
First received: September 24, 2009
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Chronic Pain
Opioid Induced Constipation
Drug: 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
Phase 2

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

Resource links provided by NLM:


Further study details as provided by S.L.A. Pharma AG:

Primary Outcome Measures:
  • Incidence and Severity of Treatment Emergent Adverse Events on Single Dosing. [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    Incidence and severity of treatment emergent adverse events on single dosing.


Enrollment: 40
Study Start Date: October 2009
Study Completion Date: April 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Capsules with no active drug
Placebo capsules once daily for three weeks then twice daily for three weeks.
Drug: Placebo
n/a
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
n/a
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
n/a
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
n/a
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
n/a

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00984334

Locations
Germany
Schmerzzentrum Berlin
Berlin, Germany, 10435
Schmerzzentrum Frankfurt
Frankfurt, Germany, 60311
Gemeinschaftspraxis Tamm-Albert-Schroter-Uhmann
Hannover, Germany, 30167
Gemeinschaftspraxis Loewenstein-Hesselbarth
Mainz, Germany, 55116
Regionales Schmerzzentrum Wuppertal
Wuppertal, Germany, 42105
United Kingdom
St Jame's Hospital Leeds
Leeds, United Kingdom, LS9 7TF
Norfolk & Norwich Hospital
Norwich, United Kingdom, NR4 7UY
Department of Pain Management, York Hospital
York, United Kingdom, LS14 6UH
Sponsors and Collaborators
S.L.A. Pharma AG
Investigators
Principal Investigator: Karen Simpson, MD St James University Hospital, Leeds, UK
  More Information

No publications provided

Responsible Party: S.L.A. Pharma AG
ClinicalTrials.gov Identifier: NCT00984334     History of Changes
Other Study ID Numbers: NAL-OIC-01, 2009-009377-10
Study First Received: September 24, 2009
Results First Received: November 7, 2013
Last Updated: November 7, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by S.L.A. Pharma AG:
pain
opioid
constipation
Subjects taking opioids for chronic non-cancer pain, who
experience symptoms of opioid induced constipation

Additional relevant MeSH terms:
Constipation
Chronic Pain
Signs and Symptoms, Digestive
Signs and Symptoms
Pain
Neurologic Manifestations
Nervous System Diseases
Naloxone
Analgesics, Opioid
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Narcotics
Central Nervous System Depressants
Analgesics

ClinicalTrials.gov processed this record on July 31, 2014