A confirmatory, placebo-controlled, randomised, double-blind, single-dummy, parallel group, ratio-finding study in constipated pain patients to establish an optimal hydromorphone â¤* naloxone ratio with an improved bowel function and a comparable analgesic efficacy compared to hydromorphone alone

Phase 3

Completed

Conditions: pijnbestrijding
cancer related background pain
chronic cancer pain
10017977
10027656

Registration Number: NL-OMON37097

Lead Sponsor: Mundipharma

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

1. Male or female subjects at least 18 years (females less than one year post-menopausal must have a negative serum or urine pregnancy test 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 sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasoectomised partner).
2. Subjects who are receiving WHO step II or step III analgesic medication for the treatment of non-cancer or cancer pain.
3. Documented history of non-cancer or cancer pain that requires opioid therapy (8, 24 or 48 mg hydromorphone PR per day for the duration of the study).
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 less than 3 bowel evacuations when not taking a laxative, respectively.
* In the opinion of the subject and Investigator it is confirmed 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.
6. Subjects must be willing to discontinue their current laxative regimen and willing to comply with the use of oral bisacodyl as laxative rescue medication.
7. 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.
8. Subjects must be willing and able (e.g. mental and 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, and compliance with protocol requirements 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, and 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.

Exclusion Criteria

1. Any history of hypersensitivity to hydromorphone, naloxone, bisacodyl, related products or other ingredients of the study medication.
2. Any contraindication to hydromorphone, naloxone, bisacodyl, related products and other ingredients of the study medication.
3. Active alcohol or drug abuse and/or history of opioid abuse.
4. Evidence of clinically significant cardiovascular, renal, hepatic, gastrointestinal (e.g. paralytic ileus), 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.
5. Chronic or intermittent pain that results from Fibromyalgia or Rheumatoid Arthritis.
6. 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.
7. Subjects with uncontrolled seizures or convulsive disorder.
8. Surgery within 2 months prior to the start of the Screening Period, or planned surgery during the 8-week Maintenance Phase that may affect GI motility or pain.
9. Subjects presently taking, or who have taken, naloxone * 30 days prior to the start of the Screening Period.
10. Subjects suffering from diarrhoea.
11. Subjects with any situation in which opioids are contraindicated (e.g., severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, paralytic ileus).
12. Subjects with hypothyroidism, Addison`s disease, increase of intracranial pressure.
13. Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels (> 3 times the upper limit of normal)
14. Abnormal total bilirubin and/or creatinine level(s) (greater than 1.5 times the upper limit of normal), gamma glutamyl transpeptidase (GGT or GGTP) * 5 times the upper limit of normal.