Moderate to severe chronic non-malignant pain that requires around-the-clock opioid therapy and also have constipation secondary to opioid treatment. MedDRA version: 7.1 Level: pt Classification code 10003988
Conditions
Sponsors
Mundipharma Research GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who are to be included in the study are those who meet all of the following screening 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 serum 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, sexual abstinence or vasoectomised partner. 3. Moderate to severe chronic nonmalignant pain that requires around-the-clock opioid therapy (oxycodone equivalent of 60 - 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 must be willing to discontinue their current opioid analgesic routine. 6. Subjects must report constipation caused or aggravated by opioids. 7. Subjects must be willing to discontinue their current laxative regimen. 8. Subjects must comply with the use of oral bisacodyl as laxative rescue medication. Rescue will be permitted no sooner than 72 hours after the subject’s most recent bowel movement (BM). 9. Subjects taking daily fiber 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. 10. 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. 11. Subjects with pre-study, non-opioid analgesics, and all other concomitant medications, including those medications for the treatment of depression, that are thought to be stable, are considered necessary for the subject’s welfare, 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects who are to be excluded from the study are those who meet any of the following screening criteria: 1. Females who are pregnant (positive ß-hCG test) or lactating. 2. Any history of hypersensitivity to oxycodone, naloxone, related products, and other ingredients. 3. Any contraindication to bisacodyl and other ingredients 4. Subjects with evidence of significant structural abnormalities of the gastrointestinal (GI) tract (e.g., bowel obstruction, strictures) or any diseases/conditions that affect bowel transit (e.g., ileus, hypothyroidism). 5. Subjects with cancer associated pain. 6. Active alcohol or drug abuse and/or history of opioid abuse. 6a. Subjects with a positive urine drug test at screening visit 1, which indicates unreported illicit drug use or unreported use of a concomitant medication not required to treat the subjects medical condition(s). 7. Subjects with Rheumatoid Arthritis (RA). 8. Subjects with evidence of clinically unstable disease, as determined by medical history, clinical laboratory tests, ECG results, and physical examination that, in the investigator’s opinion, preclude entry into the study. 9. 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 > 2 mg/dl, or in the investigator’s opinion, liver and/or kidney impairment to the extent that the subject should not participate in this study. 10. Subjects who have required treatment for the diagnosis of irritable bowel syndrome (IBS). 11. 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. 12. Subjects receiving opioid substitution therapy for opioid addiction (e.g., methadone or buprenorphine). 13. Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days of study entry (defined as the start of the Screening Period). 14. Subjects presently taking, or who have taken naloxone or naltrexone within 30 days of study entry (defined as the start of the Screening Period). 15. Surgery within 2 months prior to the start of the Screening Period, or planned surgery during the12-week Double-blind Phase that may affect GI motility or pain. 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: The primary objective of this study is to demonstrate that subjects with moderate to severe non malignant 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: The secondary objectives are: • To demonstrate that subjects taking OXN have improvement in symptoms of constipation as measured by the Patient Assessment of Opioid Induced Constipation summary score (PACOI; the mean of the summary scores from the rectal and stool subscales of the PAC-SYM) than subjects taking OXY tablets alone. • To compare the subjects’ overall opinion of their improvement with treatment over the course of the Double-blind Phase following treatment with OXN compared with OXY as measured by the Patient Global Impression of Change (PGIC). • To estimate the subjects’ Average Pain over the last 24 Hours assessed at each double-blind study visit during treatment with OXN compared with OXY as measured by the Pain Intensity Scale. • To assess subject assessment of opioid-induced constipation, constipation symptom severity, impact and bothersomeness based on the PAC-SYM(b). ;Primary end point(s): A subject’s Bowel Function Index (BFI) score will be the mean of the following items (assessed at each visit): - 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). Each of the above questions refers to the last 7 days for the subject. | — |
Countries
Czech Republic, Finland, Germany, Hungary, Spain, United Kingdom
Outcome results
None listed