A clinical trial to assess the effectiveness of oxycodone/naloxone combination drug on severe, ongoing, uncontrolled low back pain and opioid induced constipation, in patients already taking opioids for the management of this pain.
- Conditions
- Opioid-induced Constipation & Moderate to Severe Chronic Low back PainMedDRA version: 17.0Level: PTClassification code 10003988Term: Back painSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersMedDRA version: 17.0Level: LLTClassification code 10071128Term: Opioid induced constipationSystem Organ Class: 100000004856Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]
- Registration Number
- EUCTR2011-005060-26-CZ
- Lead Sponsor
- Purdue Pharma L.P.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
1. Male and female subjects = 18 years of age with moderate to severe, chronic low back pain (lasting at least several hours daily) as their predominant pain condition for at least 3 months prior to screening period.
2. The low back pain must be related to nonmalignant and
nonneuropathic conditions and may be with or without radiaton (Quebec
Task Force Classification 1 to 3)
3. Subjects must be - On ongoing opioid analgesic medication for at least 4 weeks prior to the screening visit (visit 1) and on a stable dose of opioid analgesic medication equivalent to 20 to 160 mg (inclusive) of morphine per day for the last 2 weeks prior to the screening visit (visit 1)
or
Taking 0 to less than 20 mg of morphine or its equivalent per day for the last 2 weeks prior to the screening visit (visit 1) due to OIC
4. Subjects must require opioid analgesic treatment in the range of 40 to 160 mg (inclusive) of morphine or its equivalent daily and be likely to benefit from chronic around-the-clock opioid therapy for the duration of the study.
5. Subjects must have an average pain over the last 14 days score = 5 at the screening visit
6. Subjects must have an average pain over the last 24 hours score = 5 at the screening visit
7. Subjects must have a self-reported history of OIC, defined as having
had while on opiods <3 complete spontaneous bowel movements
(CSBM) per week and 1 or more of the following for at 25% of bowel
movements (BMs):
- hard or lump stools
- straining during bowel movements
- A sensation of incomplete evacuation after bowel movements
A CSBM is defined as a spontaneous bowel movement (SBM) that is
accompanied by the subject self-reporting a feeling of complete
evacuation. An SBM is defined as a bowel movement occuring in the
absence of laxative or enema use in the previous 24h.
8. Subjects must be willing to discontinue their current laxative regimen
9. Subjects must agree to the use of oral bisacodyl as their only laxative rescue medication.
10. For subjects receiving adjunct therapy such treatment must be stopped before treatment with OXY is initiated, or, if continued, the treatment should have been at a stable dose/intensity and frequency for 2 weeks before the
screening visit (visit 1) and remain unchanged during the study.
11. If taking oral corticosteroids, subjects must be on at a stable dose for at least 6 weeks before the screening visit (visit 1) and be willing to maintain that dose throughout the study.
12. Female subjects who are premenopausal or postmenopausal less than 1 year, or who have not had surgical sterilization must have a negative serum pregnancy test
13. Subjects who are willing and able to be compliant with the protocol, and who provide written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 599
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
1. Subjects with any contraindication or any history of hypersensitivity
to oxycodone, naloxone, or other opioids.
2. Subjects with any contraindication to bisacodyl.
3. Subjects with neurologic signs, or presumptive or confirmed
compression of a spinal nerve root (i.e., Quebec Task Force Classification
4 to 6)
4. Subjects with acute spinal cord compression, acute compression fracture, seronegative spondyloarthropathy, acute nerve root compression, cauda equina compression, fibromyalgia, reflex sympathetic dystrophy or causalgia (complex regional pain syndrome), diabetic amyotrophy, meningitis, discitis, or back pain due to secondary infection, tumor, or postherpetic neuralgia.
5. Subjects with gout, unless controlled on stable suppressive treatment
with colchicine or uricacid-lowering therapy without any attacks for = 2 years and the subject has not been using NSAIDs or COX-2 inhibitors on a regular basis.
6. Subjects with pseudogout, psoriatic arthritis, active Lyme disease,
rheumatoid arthritis or other inflammatory arthritis, or neuropathic conditions that have been painful or required therapy within the last 3 months
7. Subjects who, in the opinion of the investigator, are exhibiting significant opioid withdrawal such that they should not be in the study.
8. Subjects with evidence of significant structural abnormalities of the gastrointestinal tract (e.g., bowel obstruction, strictures) or any diseases/conditions that affect bowel transit (e.g., ileus, uncontrolled hypothyroidism).
9. Subjects with a history of prior chronic constipation (including functional constipation or pelvic floor dyssynergy) that was present for more than three months and that was not related to opioid use.
10. Subjects currently with clinically diagnosed diarrhea, defined as 3 stools/day that are loose or watery in nature within 2 weeks before visit 2.
11. Subjects with irritable bowel syndrome (IBS) or inflammatory bowel disease (eg, ulcerative colitis, Crohn‘s disease).
12. Subjects who had surgery that may affect gastrointestinal motility or gastrointestinal pain within 2 months prior to the start of the screening period, or who plan such surgery during the study.
13. Subjects with a history of fecal incontinence.
14. Subjects who require ongoing therapy with medications (other than opioids) that have contributed to the subjects‘ constipation in the judgment of the investigator.
15. Subjects with hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
16. Subjects who cannot or will not agree to completely stop all incoming opioid and nonopioid analgesic medications and other medications used for chronic pain
17. Subjects who cannot or will not agree to forego the following
treatments during the study: nerve/plexus blocks or ablation in the
lumbar spine, neurosurgical procedures for pain control in the lumbar
spine, Botulinum toxin injections for pain control in the lumbar spine,
steroid injections in the lumbar spine, or inhalation analgesia
18. Subjects who had surgical procedures directed towards the source of chronic low back pain within 6 months of the screening visit (visit 1) or planned during the study.
19. Subjects with a history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated.
20. Subjects with current uncontrolled depression or other uncontrolled psychiatric disorder
21. Subjects with an average QTcF of
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the analgesic efficacy of OXN compared to placebo in opioid-experienced subjects with moderate to severe low back pain and opioid-induced constipation who require around-the-clock opioid therapy.<br><br>;Secondary Objective: To assess the safety and tolerability of OXN in opioid-experienced subjects with moderate to severe low back pain and opioid-induced constipation who require around-the-clock opioid therapy.<br><br>To assess the analgesic efficacy of OXN compared to placebo in opioidexperienced subjects with moderate to severe low back pain and opioidinduced constipation who require around-the-clock opioid therapy.;Primary end point(s): Average pain over the last 24 hours” obtained at visits 5 through 8 (weeks 2 through 12) during the double-blind period<br><br>and<br><br>Overall spontaneous bowel movements (SBM) responder rates over the 12 week double-blind period;Timepoint(s) of evaluation of this end point: NA
- Secondary Outcome Measures
Name Time Method Secondary end point(s): -SBM Responder at least 50% of the weeks in the double-blind period<br><br>-Laxative-free Responder at least 50% of the weeks in the double-blind<br><br>-Sleep Disturbance Subscale of the MOS Sleep Scale (assessed at visits 2, 3, 6, 7, and 8)<br><br>-PGIC (assessed at visit 8 or at the time of early study discontinuation or study drug discontinuation);Timepoint(s) of evaluation of this end point: NA