A Study of Oxycodone/Naloxone Controlled-release Tablets (OXN) to Assess Analgesic Efficacy and Management of Opioid-induced Constipation (OIC) in Opioid-experienced Subjects With Moderate to Severe Chronic Low Back Pain

This study is currently recruiting participants.
Verified March 2014 by Purdue Pharma LP
Sponsor:
Information provided by (Responsible Party):
Purdue Pharma LP
ClinicalTrials.gov Identifier:
NCT01427283
First received: August 30, 2011
Last updated: March 21, 2014
Last verified: March 2014
  Purpose

The primary objectives are to assess the analgesic efficacy of Oxycodone/Naloxone Controlled-release Tablets (OXN) compared to placebo and to assess the efficacy of OXN for the management of Opioid-induced Constipation (OIC) compared to Oxycodone Controlled-release Tablets (OXY) in subjects with moderate to severe pain due to chronic low back pain who require around-the-clock opioid therapy.


Condition Intervention Phase
Low Back Pain
Drug: Oxycodone/Naloxone controlled-release
Drug: Oxycodone HCl controlled-release
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Double-dummy, Placebo-controlled, Active-controlled, Parallel-group, Multicenter Trial of Oxycodone/Naloxone Controlled-release Tablets (OXN) to Assess the Analgesic Efficacy (Compared to Placebo) and the Management of Opioid-induced Constipation (Compared to Oxycodone Controlled-release Tablets (OXY)) in Opioid-experienced Subjects With Moderate to Severe Chronic Low Back Pain and a History of Opioid-induced Constipation Who Require Around-the-clock Opioid Therapy

Resource links provided by NLM:


Further study details as provided by Purdue Pharma LP:

Primary Outcome Measures:
  • The "average pain over the last 24 hours" score at week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The "average pain over the last 24 hours" score at week 12 of the double-blind period comparing OXN to placebo. The score is based on an 11-point numerical rating scale (NRS): 0 = no pain, 10 = pain as bad as you can imagine.

  • Overall complete spontaneous bowel movement (CSBM) responder rates [ Time Frame: Weeks 1 through 12 ] [ Designated as safety issue: No ]
    The overall Complete Spontaneous Bowel Movement (CSBM) responder rates over the 12 week double-blind period comparing OXN to OXY


Secondary Outcome Measures:
  • Sleep Disturbance Subscale of the Medical Outcomes Study (MOS) Sleep Scale [ Time Frame: Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
  • Patient Global Impression of Change (PGIC) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • CSBM Responder at least 50% of the weeks in the double-blind period [ Time Frame: Weeks 1 through 12 ] [ Designated as safety issue: No ]
  • Laxative-free Responder at least 50% of the weeks in the double-blind period [ Time Frame: Weeks 1 through 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 900
Study Start Date: August 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OXN
Oxycodone/Naloxone controlled-release tablets (OXN)
Drug: Oxycodone/Naloxone controlled-release
Oxycodone/Naloxone controlled-release tablets (10/5 - 40/20 mg) taken orally every 12 hours
Active Comparator: OXY
Oxycodone HCl controlled-release tablets (OXY)
Drug: Oxycodone HCl controlled-release
Oxycodone HCl controlled-release tablets (10 - 40 mg) taken orally every 12 hours
Other Name: OxyContin
Placebo Comparator: Placebo
Placebo tablets to match OXN or OXY
Drug: Placebo
Placebo tablets to match OXN or OXY taken orally every 12 hours

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria include:

  • 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;
  • The low back pain must be related to nonmalignant and nonneuropathic conditions and may be with or without radiation;
  • Subjects must be:

    1. On ongoing opioid analgesic medication for at least 4 weeks prior to the screening visit 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, or
    2. Taking 0 to less than 20 mg of morphine or its equivalent per day for the last 2 weeks prior to the screening visit due to OIC.

Subjects taking any dose of tramadol or wearing ≤ 70 mcg/h buprenorphine patch (as long as it does not exceed highest approved dose for buprenorphine in the country the study site is located) on a stable regimen for the last 2 weeks prior to the screening visit will also meet this criterion;

  • For subjects on <40 mg of morphine or equivalent per day, both the "average pain over the last 24 hours" and the "average pain over the past 14 days" scores at the screening visit must be ≥ 5;
  • Subjects must have a self-reported history of OIC as defined by having had while on opioids <3 complete spontaneous bowel movements (CSBMs) per week and 1 or more of the following for at least 25% of bowel movements (BMs):

    1. Hard or lumpy stools
    2. Straining during bowel movements
    3. 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 occurring in the absence of laxative or enema use in the previous 24 hours;

  • Subjects must be willing to discontinue their current laxative regimen, including prokinetic drugs (e.g., metoclopramide);
  • Subjects must agree to the use of oral bisacodyl as their only laxative rescue medication;
  • Subjects who are willing and able to be compliant with the protocol, and who provide written informed consent.

Exclusion Criteria include:

  • Subjects with any contraindication or any history of hypersensitivity to oxycodone, naloxone, or other opioids. This does not include subjects who have experienced common opioid side effects (e.g., nausea, constipation);
  • Subjects with neurologic signs, or presumptive or confirmed compression of a spinal nerve root;
  • 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;
  • Subjects with gout, unless controlled on stable suppressive treatment with colchicine or uric-acid-lowering therapy without any attacks for ≥ 2 years and the subject has not been using NSAIDs or COX-2 inhibitors on a regular basis;
  • Subjects with pseudogout, psoriatic arthritis, active Lyme disease, rheumatoid arthritis or other inflammatory arthritis. Subjects with neuropathic conditions that have been painful or required therapy (such as gabapentin or other neuropathic pain treatments) within the past 3 months are also excluded;
  • 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);
  • 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;
  • Subjects currently with clinically diagnosed diarrhea, defined as 3 stools/day that are loose or watery in nature within 2 weeks before visit 3;
  • Subjects with irritable bowel syndrome (IBS) or inflammatory bowel disease (eg, ulcerative colitis, Crohn's disease);
  • 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;
  • Subjects with a history of fecal incontinence;
  • Subjects who require ongoing therapy with medications (other than opioids) that have contributed to the subjects' constipation in the judgment of the investigator;
  • The subject must not have had any of the following within the indicated time periods before screening:

    • nerve/plexus block in the lumbar spine within 4 weeks
    • neuroablation in the lumbar spine within 6 weeks
    • Botulinum toxin injection for pain control in the lumbar spine within 3 months
    • steroid injections of the lumbar spine within 6 weeks or any intravenous or intramuscular steroid injections within 4 weeks;
  • Subjects who had surgical procedures directed towards the source of chronic low back pain within 6 months of the screening visit or planned during the study;
  • Subjects with a history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated;
  • Subjects with current uncontrolled depression or other uncontrolled psychiatric disorder (subjects with controlled depression or other psychiatric disorder must be on stable medication for at least 1 month prior to the screening visit to participate in the study);
  • Subjects currently taking, or who have taken naloxone, naltrexone, methylnaltrexone, or alvimopan within 10 days before the screening visit;
  • Subjects who have used any investigational medication within 30 days prior to the first dose of study medication;
  • Subjects who had received a monoamine oxidase inhibitor within the last 14 days prior to the screening visit;
  • Subjects with any condition in which opioids are contraindicated, such as severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, or paralytic ileus;
  • Subjects with increase of intracranial pressure and/or epilepsy (not including history of pediatric febrile seizures);
  • Subjects with clinically significant cardiovascular disease or dysrhythmias;
  • Subjects with biliary tract disease, hypothyroidism, adrenal cortical insufficiency, or any other medical condition that in the investigator's opinion is inadequately treated and precludes entry into the study;
  • Subjects who, in the opinion of the Investigator, are unsuitable to participate in this study for any other reason;
  • Subjects who have received study drug in a clinical study of OXN or ONU.

Other protocol specific inclusion/exclusion criteria may apply.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01427283

Contacts
Contact: Patient Recruitment Specialist 1-855-253-3456 convergestudy@quintiles.com

  Show 198 Study Locations
Sponsors and Collaborators
Purdue Pharma LP
  More Information

No publications provided

Responsible Party: Purdue Pharma LP
ClinicalTrials.gov Identifier: NCT01427283     History of Changes
Other Study ID Numbers: ONU3705, 2011-005061-20
Study First Received: August 30, 2011
Last Updated: March 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Purdue Pharma LP:
Low back pain
Chronic pain
Opioid
Constipation
Moderate to severe

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

ClinicalTrials.gov processed this record on April 16, 2014