Chronic PainPhase 2NCT00984334
Naloxone SR Capsules in Patients With Opioid Induced Constipation
A Phase 2 study testing Naloxone SR 5 mg capsules, Naloxone SR 10 mg capsules and Naloxone SR 20mg capsules in people with Chronic Pain and Opioid Induced Constipation, run by S.L.A. Pharma AG at 8 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Pain, Opioid Induced Constipation
- What is being tested?
- Naloxone SR 5 mg capsules, Naloxone SR 10 mg capsules and Naloxone SR 20mg capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Oct 2009to Apr 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Germany5 sites
Schmerzzentrum Berlin
Berlin, 10435
Schmerzzentrum Frankfurt
Frankfurt, 60311
Gemeinschaftspraxis Tamm-Albert-Schroter-Uhmann
Hanover, 30167
Gemeinschaftspraxis Loewenstein-Hesselbarth
Mainz, 55116
Regionales Schmerzzentrum Wuppertal
Wuppertal, 42105
United Kingdom3 sites
St Jame's Hospital Leeds
Leeds, LS9 7TF
Norfolk & Norwich Hospital
Norwich, NR4 7UY
Department of Pain Management, York Hospital
York, LS14 6UH
About this study
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
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.
Read the 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.
- Conditions
- Chronic Pain, Opioid Induced Constipation
- Being tested
- Naloxone SR 5 mg capsules, Placebo, Naloxone SR 10 mg capsules, Naloxone SR 20mg capsules, Naloxone SR 2.5 mg capsules
- Keywords
- pain, opioid, constipation, Subjects taking opioids for chronic non-cancer pain, who, experience symptoms of opioid induced constipation
- Medical subject headings
- Chronic Pain, Opioid-Induced Constipation, Pain, Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naloxone SR 5 mg capsulesDrug
PlaceboDrug
Naloxone SR 10 mg capsulesDrug
Naloxone SR 20mg capsulesDrug
Naloxone SR 2.5 mg capsulesDrug
| Study group | Role | What they receive |
|---|---|---|
| Capsules with no active drug | Placebo comparator | Placebo capsules once daily for three weeks then twice daily for three weeks. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Naloxone SR 5 mg capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and Severity of Treatment Emergent Adverse Events on Single Dosing.
Incidence and severity of treatment emergent adverse events on single dosing.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2009 (estimated)
- Study startOct 2009
- Primary completionJan 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- S.L.A. Pharma AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Karen Simpson, MD, Principal investigator, St James University Hospital, Leeds, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00984334
- Sponsor's protocol ID
- NAL-OIC-01
- Other IDs
- 2009-009377-10, 2009
- Status last verified
- Nov 2013
- First submitted
- 24 Sep 2009
- Last updated
- 27 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00984334
- Acronym / sponsor ID
- NAL-OIC-01
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- S.L.A. Pharma AGIndustry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- Jan 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 25 Sep 2009 (estimated)
- Results
- Posted 27 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Capsules with no active drug | Placebo comparator | Drug: PlaceboPlacebo capsules once daily for three weeks then twice daily for three weeks. |
| Naloxone SR 2.5 mg capsules | Active comparator | Drug: Naloxone SR 2.5 mg capsulesNaloxone SR 2.5 mg capsules once daily for three weeks then twice daily for three weeks. |
| Naloxone SR 10mg capsules | Experimental | Drug: Naloxone SR 10 mg capsulesNaloxone SR 10 mg capsules once daily for three weeks then twice daily for three weeks. |
| Naloxone SR 20 mg capsules | Experimental | Drug: Naloxone SR 20mg capsulesTwo Naloxone SR 10 mg capsules once daily for three weeks then twice daily for three weeks. |
| Naloxone SR 5mg capsules | Experimental | Drug: Naloxone SR 5 mg capsulesNaloxone SR 5 mg capsules once daily for three weeks then twice daily for three weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen Simpson, MD principal investigator
St James University Hospital, Leeds, UK
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naloxone SR 5 mg capsules, Naloxone SR 10 mg capsules and Naloxone SR 20mg capsules in people with Chronic Pain and Opioid Induced Constipation, run by S.L.A. Pharma AG at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and Severity of Treatment Emergent Adverse Events on Single Dosing. (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2013.