A study to demonstrate improvement in symptoms of constipation and non-inferiority in analgesic efficacy in subjects with non-malignant or malignant pain that requires around-the-clock opioid therapy taking oxycodone/naloxone prolonged release (OXN PR) tablets compared to subjects taking oxycodone prolonged release (OxyPR) tablets alone.

Phase 1

• Conditions: The intended indication is:Severe pain, which can be adequately managed only with opioid analgesics. The opioid antagonist naloxone is added to counteract opioid-induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut.; MedDRA version: 14.1Level: PTClassification code 10058019Term: Cancer painSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]; MedDRA version: 14.1Level: PTClassification code 10033371Term: PainSystem Organ Class: 10018065 - General disorders and administration site conditions

• Registration Number: EUCTR2010-021995-27-RO
• Lead Sponsor: Mundipharma Research GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-01-18
• Study Completion: 2014-02-10
• Last Update Posted: 17 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 243

Inclusion Criteria

1. Male or female subjects at least 18 years (females 2. Subjects who are receiving WHO step III opioid analgesic medications for the treatment of non-malignant or malignant pain.
3. Documented history of non-malignant or malignant pain that requires around-the-clock opiod therapy (100-160mg oxycodone PR per day for a minimum of 5 weeks).
4. subjects with constipation caused or aggravated by opioids:
- Subject's medical need of regular intake of laxatives to have at least 3 bowel evacuations per week, or having - In the opinion of the Subject & investigator confirm that the subject's constipation is induced or worsened by the subject's pre-study opioid medication (present at screening).
5. Subjects must be willing to discontinue their current opioid analgesic routine & willing to comply with the use of opioid study medication.
6. Subjects must be willing to discontinue their current laxative regimen & willing to comply with the use of oral bisacodyl as lacative rescue medication.
7. Subjects taking daily fibre supplementation or bulking agents are eligible if they can be maintained on a stable dose & regimen throughout the study, & in the investigator's opinion are willing & able to maintain adequate hydration.
8. Subjects must be willing & able (eg. mental & physical condition) to participate in all aspects of the study, including use of medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts & compliance with protocol requirments as evidenced by providing written, informed consent.
9. In the investigator's opinion the subject's non-analgesic concomitant medications, including those medications for the treatment of depression are thought to be stable & will remain stable throughout the double-blind phase of the study.
10. In the investigator's opinion the non-opioid analgesic medication dose will remain stable during the double-blind phase.
11. Subjects who are dissatisfied (lack of efficacy or unacceptable tolerability) with their current WHO step III opioid analgesic medication.
12. Criteria for entry into Run-in Period:
- Subjects continue to satisfy Screening Inclusion/Eclusion criteria.
13. Criteria for entry into the Double-blind Phase:
- Subjects continue to satisfy Screening Inclusion/Exclusion criteria
- Subjects should be on a stable dose of 50, 60, 70 or 80 mg oxycodone PR twice daily on at least 4 consecutive days prior to randomisation.
- Subjects must rate their pain (Average Pain over last 24 Hours) as - Subjects must have confirmed opioid related constipation, which is defined as having <3 CSBM-NSs during the last 7 days of the Run-in Period.
- Subjects demonstrate compliance with rescue medication use (OxyIR), oral bisacodyl), taking

Exclusion Criteria

1. Any history of hypersensitivity to oxycodone, naloxone, related products, bisacodyl or other ingredients of the study medication.
2. Any contraindication to oxycodone, naloxone, bisacodyl and other ingredients of the study medication.
3. Active alcohol or drug abuse and/or history of opioid abuse.
4. Subjects with a +ve urine drug test at screeing Visit 1, which indicates unreported illicit drug use or unreported use of a concomitant medication not required to treat the subject's medical condition(s).
5. Evidence of clinically significant cardiovascular, renal, hepatic, gastrointestinal (eg. paralytic ileus) or psychiatric disease, as determined by medical history, clinical laboratory tests, ECG results & 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 resulrs.
6. Chronic or intermittant pain that results from Fibromyalgia or Rheumatoid Arthritis.
7. 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 opioid study medication.
8. Subjects with uncontrolled seizures or convulsive disorder.
9. Surgery within 2 months prior to the start of the Screening Period, or planned surgery during the 5-week Double-blind Phase that may affect GI motility or pain.
10. Subjects presently taking, or who have taken, naloxone or methylnaltrexone 11. Subjects suffering from diarrhoea.
12. Subjects with any situation in which opioids are contraindicated e.g, severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, parlaytic ileus.
13. Subjects with hyperthyroidism (non-compensated), addison's disease, increase of intracranial pressure.
14. Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase lavels (>3 times the upper limit of normal) or an abnormal total bilirubin and/or creatinine level(s) (>1.5 times the upper limit of normal), gamma glutamyl transpeptidase (GGT or GGTP) >/= 3 time the upper limit of normal. Bilirubin or creatinine values below the lower limit of normal are not necessarility a criterion for an improvement of organ function. Therefore values out of the lower normal range do not automatically lead to an exclusion of the subject from the study. The decision to discontinue a subject from the study due to bilirubin or creatinine level below the lower limit of normal should be based on the medical judgement of the investigator. Furthermore the decision should also be based on the presence or absence of pathophysiological impairment of respective organs.
15. Subjests presently taking or who have taken monoamine oxidase inhibitors (MAOI)
Exclusion criteria for subjects suffering from non-malignant pain:
16. Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days of study entry (start of Screening Period).

Exclusion criteria for subjects suffering from cancer pain:
17. Subjects with known or suspected unstable brain metastases or spinal cord compression that may require changes in steroid treatment throughout the duration of the study.
18. Cyclic chemotherapy in the 2 weeks before the screening visit or planne

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified