Naloxone SR Capsules in Patients With Opioid Induced Constipation

NCT00984334 | Completed Phase 2 Results

• 2 other identifiers: NAL-OIC-012009-009377-10
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 8

Brief 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.

Conditions

Chronic Pain; Opioid Induced Constipation

Keywords

pain; opioid; constipation; Subjects taking opioids for chronic non-cancer pain, who; experience symptoms of opioid induced constipation

Outcome Measures

Primary Outcomes (1)

• Incidence and Severity of Treatment Emergent Adverse Events on Single Dosing.

  Incidence and severity of treatment emergent adverse events on single dosing.

  3 weeks

Study Arms (5)

Capsules with no active drug

PLACEBO COMPARATOR

Placebo capsules once daily for three weeks then twice daily for three weeks.

Drug: Placebo

Naloxone SR 2.5 mg capsules

ACTIVE COMPARATOR

Naloxone SR 2.5 mg capsules once daily for three weeks then twice daily for three weeks.

Drug: Naloxone SR 2.5 mg capsules

Naloxone SR 10mg capsules

EXPERIMENTAL

Naloxone SR 10 mg capsules once daily for three weeks then twice daily for three weeks.

Drug: Naloxone SR 10 mg capsules

Naloxone SR 20 mg capsules

EXPERIMENTAL

Two Naloxone SR 10 mg capsules once daily for three weeks then twice daily for three weeks.

Drug: Naloxone SR 20mg capsules

Naloxone SR 5mg capsules

EXPERIMENTAL

Naloxone SR 5 mg capsules once daily for three weeks then twice daily for three weeks.

Drug: Naloxone SR 5 mg capsules

Interventions

Naloxone SR 5 mg capsules DRUG

Naloxone SR 5mg capsules

Placebo DRUG

Capsules with no active drug

Naloxone SR 10 mg capsules DRUG

Naloxone SR 10mg capsules

Naloxone SR 20mg capsules DRUG

Naloxone SR 20 mg capsules

Naloxone SR 2.5 mg capsules DRUG

Naloxone SR 2.5 mg capsules

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• S.L.A. Pharma AG: lead

Study Sites (8)

Schmerzzentrum Berlin

Berlin, 10435, Germany

Location

Schmerzzentrum Frankfurt

Frankfurt, 60311, Germany

Location

Gemeinschaftspraxis Tamm-Albert-Schroter-Uhmann

Hanover, 30167, Germany

Location

Gemeinschaftspraxis Loewenstein-Hesselbarth

Mainz, 55116, Germany

Location

Regionales Schmerzzentrum Wuppertal

Wuppertal, 42105, Germany

Location

St Jame's Hospital Leeds

Leeds, LS9 7TF, United Kingdom

Location

Norfolk & Norwich Hospital

Norwich, NR4 7UY, United Kingdom

Location

Department of Pain Management, York Hospital

York, LS14 6UH, United Kingdom

Location

MeSH Terms

Conditions

Chronic Pain; Opioid-Induced Constipation; Pain; Constipation

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Limitations and Caveats

Small number of subjects per group.

Results Point of Contact

• Title: Dr C Jordan, Head of Clinical Operations
• Organization: S.L.A. Pharma UK Ltd

cjordan@slapharma.com

44 01923 681001

Study Officials

• Karen Simpson, MD

  St James University Hospital, Leeds, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2009
• First Posted: September 25, 2009
• Study Start: October 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: April 1, 2012
• Last Updated: December 27, 2013
• Results First Posted: December 27, 2013

Record last verified: 2013-11

Locations

DE (5); GB (3)