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: 16.1 Level: PT Classification code 10058019 Term: Cancer pain System Organ Class: 10029104 - Neoplasms benign, malignant and
Conditions
Interventions
Trade Name: Targinact 10mg / 5mg
Product Name: oxycodone/naloxone 10 mg / 5 mg prolonged release tablet
Product Code: OXN PR 10/5 mg
Pharmaceutical Form
Sponsors
Mundipharma Research GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects at least 18 years (females <than 1 year post-menopausal must have a -ve serum or urine pregancy test prior to the 1st dose of study medication, be non-lactating & willing to use adequate & 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. < than 1% per year, when used consistently & correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. 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 <than 3 bowel evacuations when not taking a laxative. - 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 laxative 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/Exclusion 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 </= 4 on 0-10 scale with < / = to 2 doses of OxyIR analgesic rescue medication per da
Exclusion criteria
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 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) </= 2 weeks prior to the start of the Screening Period. 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To demonstrate that subjects taking OXN PR have improvement in symptoms of constipation as measured by the Bowel Function Index (BFI) compared to subjects taking OxyPR. 2. To demonstrate non-inferiority of OXN PR compared to OxyPR with respect to the analgesic efficacy based on the subjects' "Average Pain over last 24 Hours" assessed at each Double-blind Phase visit as measured by the Pain Intensity Scale. ; Secondary Objective: 1. To assess "Average Pain over last 24 Hours" based on the Pain Intensity Scale collected daily in the subject diary during the Double-blind Phase. 2. To assess analgesic rescue medication use. 3. To assess laxative rescue medication use. 4. To assess aspects of constipation (Complete Spontaneous Bowel Movement (CSBMs)). 5. To assess quality of life aspects based on the EuroQol EQ-5D. 6. To assess bowel function, pain and safety parameters during the extension phase. ; Primary end point(s): Assessment of constipation symptoms through measurement of Bowel Function Assessment of analgesic efficacy through measurement of Pain Intensity ; Timepoint(s) of evaluation of this end point: Core Phase Visit 7 to 10 inclusive (day 7 to 35) Extension Phase Visit 11 to 19 inclusive (day 0 to 168) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Assessment of Pain over last 24 hours Need for Analgesic rescue Need for Laxative rescue Assessment of constipation Assesment of QoL ;Timepoint(s) of evaluation of this end point: During the double-blind phase | — |
Countries
Australia, Czech Republic, Denmark, Finland, Germany, India, Israel, Korea, Republic of, Romania, United Kingdom
Contacts
Public ContactClinical Trial Contact
Mundipharma Research GmbH & Co. KG
Outcome results
None listed