Study to find the optimal hydromophone / naloxone ratio and compare bowel function and analgesic efficacy with Hydromorphone PR in patients with constipation caused by opioid treatment

• Conditions: Moderate to severe chronic non-cancer or cancer pain with opioid induced constipation; MedDRA version: 14.0Level: PTClassification code 10033371Term: PainSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 14.0Level: PTClassification code 10010774Term: ConstipationSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

• Registration Number: EUCTR2008-005315-18-CZ
• Lead Sponsor: Mundipharma Research GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05-13
• Last Update Posted: 24 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

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.
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 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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. Exclusion criteria for subjects suffering from non-cancer pain: 15. 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).
Exclusion criteria for subjects suffering from cancer/cancer pain:
16. 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.
17. Cyclic chemotherapy in the two weeks before the screening visit or planned during the study that has shown in the past to significantly influence bowel function. If subjects are having their first cycle of chemotherapy during the 2 weeks before the screening visit or during the study they should be excluded from the study.
18. Radiotherapy that, in the Investigators opinion, would influence bowel function or pain during the study.
19. 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). Concurrent enrolment in another clinical trial is not permitted unless the sole purpose of the other trial at the time of HMX3501 screening is for long-term survival data.

Study & Design

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