A randomised, double-blind, double-dummy, parallel-group multicentre study to demonstrate non-inferiority in pain and locomotor function and improvement in symptoms of constipation in subjects with moderate to severe pain due to osteoarthritis (OA) of the knee and/or hip taking oxycodone equivalent of 20 - 80 mg/day as oxycodone/naloxone prolonged release (OXN PR) compared to subjects taking oxycodone prolonged release tablets (OxyPR) alone.

Conditions: Pain, locomotor function and improvement in constipation in osteoarthritis patients taking opioids
MedDRA version: 9.1Level: LLTClassification code 10031161Term: Osteoarthritis
MedDRA version: 9.1Level: LLTClassification code 10021175Term: Iatrogenic constipation

Registration Number: EUCTR2008-002670-36-NL

Lead Sponsor: Mundipharma Research GmbH & Co. KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 200

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 for the duration of the study.
5.Subjects with a clinical diagnosis of degenerative or primary 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.Subjects who are receiving WHO step II or step III analgesic medication and in the opinion of the subject and investigator confirm that the subjects constipation is induced, or worsened by the subjects pre study opioid medication (present at Screening).
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 hours) as =4 on 0-10 scale with less than or equal to two doses of oxycodone immediate release (OxyIR) rescue medication per day (Table 1 in the protocol) for either the last three consecutive days or four of the last seven days before randomisation.
4.Subjects must have confirmed opioid related constipation, which i

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.
3.Subjects with secondary osteoarthritis (e.g. fracture, septic, agromegaly).
4.Subjects with a replacement of the most painful joint (knee or hip).
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.