A study comparing oxycodone to oxycodone/naloxone in moderate to severe, chronic cancer pain.

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12607000493448
• Date of registration: 24/09/2007
• Prospective Registration: No
• Primary sponsor: Mundipharma Research GmbH & Co KG
• Public title: A study comparing oxycodone to oxycodone/naloxone in moderate to severe, chronic cancer pain.
• Scientific title: A randomised, double-blind, active-controlled, double-dummy, parallel group study to determine the safety and efficacy of oxycodone/naloxone prolonged release tablets in subjects with moderate to severe, chronic cancer pain.
• Date of first enrolment: 27/08/2007
• Target sample size: 180
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12607000493448.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Safety/efficacy;
• Phase: Phase 2

Countries of recruitment

Australia, Czech Republic, France, Germany, Hungary, Israel, Netherlands, Poland, United Kingdom

Contacts

• Name: Jill Kiteley & Catharina Buschmann

• Name: Jill Kiteley & Catharina Buschmann

Key inclusion & exclusion criteria

Inclusion criteria: 1. Subjects with a diagnosis of cancer.
2.Females less than one year post-menopausal must have a negative urine pregnancy test recorded at the screening visit, be non-lactating, and willing to use adequate and highly effective method of contraception throughout the study. Highly effective methods of birth control are 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 (hormonal), sexual abstinence or vasectomised partner.
3.Subjects who are receiving WHO step II or Step III analgesic medication who have constipation induced, or worsened by their opioid medication, as shown by
a.the 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.
b.the subject’s self-assessment that their constipation was induced or worsened by their current pre-study opioid medication.
4.Documented history of moderate to severe, chronic cancer pain that requires around-the-clock opioid therapy (starting dose at the beginning of the double-blind phase of oxycodone PR between 20 - 80 mg/day) and are likely to benefit from WHO step III opioid therapy for the duration of the study. Subjects must be willing to discontinue their current opioid analgesic routine.
5.Subjects are willing to discontinue pre-study laxative medication and take study specific laxative medication.
6.Subjects taking daily fibre supplementation or bulking agents are eligible if they can be maintained on a stable dose and regimen throughout the study, and in the investigators opinion are willing and able to maintain adequate hydration.
7.Subjects 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.
Subjects already taking non-opioid analgesics and all other concomitant medications (including those for the treatment of depression) are eligible to take part in the study. However, all concomitant medications that are considered necessary for the subject’s welfare should be continued at a stable dose throughout the double-blind phase of the study and under the supervision of the investigator. Regarding cyclic chemotherapy please see exclusion criteria list.
Exclusion criteria: 1.Subjects that require a dose >80 mg/day oxycodone PR at the start of the double-blind phase.
2.Any history of hypersensitivity to oxycodone, naloxone, bisacodyl, related products, and other ingredients.
3.Subjects with any situation in which opioids are contra-indicated, severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive pulmonary disease, cor pulmonale, severe bronchial asthma, paralytic ileus.
4.Evidence of clinically significant cardiovascular, renal, hepatic 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.Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels (>3 times the upper limit of normal) or an abnormal total bilirubin and/or creatinine level(s) (greater than 1.5 times the upper limit of normal).
6.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.
7.Subjects with uncontrolled seizures.
8.Subjects with increased intracranial pressure.
9.In the investigator’s opinion, subjects who are receiving hypnotics or other central nervous system (CNS) depressants that may pose a risk of additional CNS depression with opioid study medication.
10.Subjects with myxodema, not adequately treated hypothyroidism or Addisons disease.
11.Active alcohol or drug abuse and/or history of opioid abuse.
12.Subjects receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine).
13.Subjects with evidence of clinically significant gastrointestinal disease (e.g. paralytic ileus, peritnoneal carcinosis), significant structural abnormalities of the gastrointestinal tract (e.g. scarring, obstruction etc) either related or not related to the underlying cancer or disease progression.
14.Subjects who have a confirmed diagnosis of ongoing irritable bowel syndrome.
15.Subjects suffering from diarrhoea and/or opioid withdrawal.
16.Surgery completed prior to the start of the Screening Period, or planned surgery during the study that would influence pain or bowel function during the study or preclude completion of the study.
17.Cyclic chemotherapy in the two weeks before the screening visit or planned during the core study that has shown in the past to influence bowel function. If subjects are having their first cycle of chemotherapy during the 2 weeks before the screening visit or during the double-blind phase of the study they should be excluded from the study.
18.Radiotherapy that, in the investigators opinion, would influence bowel function or pain during the double-blind phase of the study.
19.Subjects presently taking, or who have taken, naloxone ?30 days prior to the start of the Screening Period.
20.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).

Age minimum: 18 Years
Age maximum: Not stated
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Cancer - Other cancer types

Moderate to severe chronic cancer pain. Constipation.;
Moderate to severe chronic cancer pain.
Constipation.

Intervention(s)

Oxycodone/Naloxone prolonged release,
5/2.5, 10/5, 20/10, 40/20 mg oxycodone/naloxone combination, 12 hourly for 4 weeks, taken orally

Primary Outcome(s)

Efficacy variable:
Bowel Function Index (BFI) score.[Visit 1, Visit 2, Visit 6, Visit 7, Visit 8, Visit 9, Visit 12, Visit 13]

Amount of laxative medication use recorded at each assessment visit.[Visit 6, Visit 7, Visit 8, Visit 9]

Brief Pain Inventory Short-Form (BPI-SF) (Cleeland, 1991).[Visit 1, Visit 2, Visit 3, Visit 4, Visit 5, Visit 6, Visit 7, Visit 8, Visit 9, Visit 10, Visit 11, Visit 12, Visit 13]

Amount of analgesic rescue medication used.[Recorded Daily for 4 weeks]

Secondary Outcome(s)

PAC-SYM, a validated questionnaire assessing the symptoms of constipation.[Visit 1, Visit 2, Visit 9,
Visit 12, Visit 13]

EORTC QLQ-C30 (Quality of Life Questionnaire-Core 36).[Visit 1, Visit 9,
Visit 12, Visit 13]

Modified Subjective Opiate Withdrawal Scale (SOWS).[Visit 1, Visit 2, Visit 3, Visit 4, Visit 5, Visit 6.
V10, V11]

Number of bowel movements.[Visit 1, Visit 2, Visit 6, Visit 7, Visit 8, Visit 9, Visit 12, Visit 13]

EuroQol EQ-5D[Visit 1, Visit 9,
Visit 12, Visit 13]

PAC-SYM(b). This is an adaptation of the PAC-SYM (Frank et al. 1999), which includes the first 12 questions of the validated PAC-SYM and an additional measure of bothersomeness of the symptoms of constipation.[Visit 1, Visit 2, Visit 9,
Visit 12, Visit 13]

Secondary ID(s)

NCT00513656 ClinicalTrials.gov

Source(s) of Monetary Support

Mundipharma Research GmbH & Co KG

Ethics review

Status: Approved
Approval date:
Contact:

Bellbery Human Research Ethics Committee

Status: Approved
Approval date:
Contact:

Mater Health Services Human Research Ethics Committee

Status: Approved
Approval date:
Contact:

Sydney South West