Pain, locomotor function and improvement in constipation in osteoarthritis patients taking opioids MedDRA version: 9.1 Level: LLT Classification code 10031161 Term: Osteoarthritis MedDRA version: 9.1 Level: LLT Classification code 10021175 Term: Iatrogenic constipation
Conditions
Interventions
Product Name: oxycodone/naloxone prolonged release tablets 5/2.5 mg
Product Code: OXN PR 5/2.5 mg
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Oxycodone hydrochloride
CAS Number:
Sponsors
Mundipharma Research GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects at least 18 years or older. 2. Female subjects less than one year post-menopausal must have a negative pregnancy test recorded prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilization, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasoectomised partner. 3. Moderate to severe chronic nonmalignant OA, whose primary pain site is of the hip(s) and/or knee(s) and that require around-the-clock opioid therapy (oxycodone equivalent of 20-80 mg/day). 4. Subjects who require continuation of daily opioid treatment and are likely to benefit from WHO step III opioid therapy at least for the duration of the study. 5. Subjects with a clinical diagnosis of osteoarthritis, supported by evidence from one of the following: magnetic resonance imaging (MRI), computerized axial tomography (CAT), arthroscopy or x-ray. The clinical imaging of osteoarthritis may include one or more of the following features: joint space narrowing, degenerative changes, osteophyte formation or subchondral cysts. Subjects will identify the most painful joint (hip or knee) for documentation of OA. Pain measurement will be done at this joint only. 6. Subject and investigator confirm that the subjects constipation is induced, or worsened by the subjects pre study opioid medication (present at Screening) and needs medical treatment. Subjects suffering from pain due to secondary osteoarthritis (e.g. fracture, sepsis, acromegaly) or due to a replacement of joint (knee or hip) received a WHO step III analgesic medication for at least 4 weeks prior to study entry (Visit 1). Complications of the arthroplasty/hemiarthroplasty, like dislocation, fracture or infections must not be the cause for remaining pain in osteoarthritic joint. 7. Subjects willing and able to participate in all aspects of the core study, including use of oral medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, and compliance with protocol requirements as evidenced by providing written, informed consent and willing to discontinue their current opioid analgesic routine, laxative regimen, and comply with the use of oral bisacodyl as laxative rescue medication. 8. Subjects taking daily fibre supplementation or bulking agents are eligible if they can be maintained on a stable dose and regimen throughout the study, and in the investigator’s opinion are willing and able to maintain adequate hydration. 9. Subjects taking pre-study, non-opioid analgesics, and all other concomitant medications, including those medications for the treatment of depression and non-medical treatment, that are thought to be stable, and are considered necessary for the subject’s welfare, and are anticipated to remain stable throughout the Double-blind Period of the study, and are to be continued under the supervision of the investigator, are eligible. There are further criteria for entry to the Double Blind phase: 1. Subjects continue to satisfy Screening Inclusion/Exclusion criteria. 2. Subject’s OxyPR dose must be between 20- 80 mg/day. 3. Subjects must rate their pain (“average pain” over the last 24 hou
Exclusion criteria
Exclusion criteria: 1. Females who are pregnant (positive ß-hCG test) or lactating. 2. Subjects with any contraindication or any history of hypersensitivity to bisacodyl, oxycodone, naloxone, related products or other ingredients. 5. 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, hypothyroidism). 6. Subjects who require treatment for the diagnosis of irritable bowel syndrome (IBS); Surgery within 2 months prior to the start of the Screening Period, or planned surgery during the 12-week Double-blind Phase that may affect GI motility or pain. 7. Subjects with cancer associated pain. 8. Subjects with chronic disease of the joints of a relapsing/remitting nature or any other chronic condition causing pain likely to warrant the persistent use of escape analgesic (e.g. gout, Rheumatoid Arthritis (RA)). 9. Evidence of clinically significant cardiovascular, renal, hepatic or psychiatric disease, as determined by medical history, clinical laboratory tests, ECG results, and physical examination, that would place the subject at risk upon exposure to the study medication or that may confound the analysis and/or interpretation of the study results. 10. Subjects with evidence of impaired liver/kidney function upon entry into the study defined as aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels >3 times the upper limit of normal; gamma glutamyl transpeptidase (GGT or GGTP) =5 times the upper limit of normal; total bilirubin level outside of the reference range; and/or creatinine level outside of the reference range, or in the investigator’s opinion, liver and/or kidney impairment to the extent that the subject should not participate in this study. 11. Subjects presently taking, or who have taken naloxone or naltrexone within 30 days of study entry (defined as the start of the Screening Period). 12. Subjects receiving hypnotics or other central nervous system (CNS) depressants that, in the investigator’s opinion, may pose a risk of additional CNS depression with opioids study medication. 13. Subjects receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine). 14. Subjects with active alcohol or drug abuse and/or history of opioid abuse. 15. Subjects who have received a new chemical entity or an experimental drug within 30 days of study entry (defined as the start of the Screening Period). 16. Subjects with any situation in which opioids are contraindicated, severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, paralytic ileus. 17. Subjects with myxoedema, hypothyroidism, Addison`s disease, increase of intracranial pressure and/or epilepsy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate that the treatment with OXN PR tablets is non-inferior to the treatment with OxyPR with regards to analgesic efficacy and locomotor function as assessed by the Western Ontario and McMaster Universities Osteoarthritis Composite Index (WOMAC VA3.1, visual analogue scale) in subjects with moderate to severe OA pain. • To demonstrate that subjects with moderate to severe OA pain taking oxycodone/naloxone prolonged release tablets have improvement in symptoms of constipation as measured by the bowel function index (BFI) compared to subjects taking oxycodone prolonged release tablets alone. ;Secondary Objective: • To estimate the subjects’ average pain over the last 24 hours assessed at each double-blind study visit during treatment with OXN PR compared with OxyPR. • To assess subject assessment of opioid-induced constipation, constipation symptom severity, impact and bothersomeness based on the PAC-SYM(b). ;Primary end point(s): • Patient assessment of pain and locomotor function by the Western Ontario and McMaster Universities Osteoarthritis Composite Index (WOMAC VA3.1, visual analogue scale). • Bowel Function Index (BFI) will be the mean of the following items (assessed at each visit for the last 7 days): Ease of defecation (numerical analogue scale [NAS], 0=easy/no difficulty; 100=severe difficulty), Feeling of incomplete bowel evacuation (NAS, 0=not at all, 100=very strong), Personal judgment of constipation (NAS, 0=not at all, 100=very strong). | — |
Countries
Austria, Belgium, Czech Republic, Finland, Germany, Hungary, Netherlands, Spain
Outcome results
None listed