A Study Comparing Oxycodone to Oxycodone/Naloxone in Moderate to Severe, Chronic Cancer Pain

NCT00513656 | Completed Phase 2

• 2 other identifiers: OXN20012007-001313-42
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the oxycodone/naloxone combination compared to oxycodone alone in patient's specific type of "chronic cancer pain".

Conditions

Cancer; Pain; Constipation

Keywords

Efficacy; chronic; cancer; pain; constipation; oxycodone; naloxone; Moderate to severe chronic cancer pain

Outcome Measures

Primary Outcomes (2)

• Efficacy variable: Bowel Function Index (BFI) score. Amount of laxative medication use recorded at each assessment visit

  4 weeks and a 6 month open label

• Efficacy variable: Brief Pain Inventory Short-Form (BPI-SF) (Cleeland, 1991). Amount of analgesic rescue medication used

  4 weeks and a 6 month open label

Secondary Outcomes (6)

• Number of bowel movements

• Modified Subjective Opiate Withdrawal Scale (SOWS)

• EuroQol EQ-5D

• EORTC QLQ-C30

• PAC-SYM

Study Arms (2)

Oxycodone Hydrochloride Tablets

ACTIVE COMPARATOR

Drug: Oxycodone

Oxycodone Naloxone Tablets

EXPERIMENTAL

Drug: Oxycodone/Naloxone

Interventions

Oxycodone DRUG

Oxycodone Hydrochloride Tablets

Oxycodone/Naloxone DRUG

Oxycodone Naloxone Tablets

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects at least 18 years or older with a diagnosis of cancer.
• 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 sterilization, implants, injectables, combined oral contraceptives, some IUDs (hormonal), sexual abstinence or vasectomised partner.
• 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
• 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.
• the subject's self-assessment that their constipation was induced or worsened by their current pre-study opioid medication.
• 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.
• Subjects are willing to discontinue pre-study laxative medication and take study specific laxative medication.
• 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.
• 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.

You may not qualify if:

• Subjects that require a dose \>80 mg/day oxycodone PR at the start of the double-blind phase.
• Any history of hypersensitivity to oxycodone, naloxone, bisacodyl, related products, and other ingredients.
• 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.
• 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.
• 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).
• 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.
• Subjects with uncontrolled seizures.
• Subjects with increased intracranial pressure.
• 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.
• Subjects with myxodema, not adequately treated hypothyroidism or Addisons disease.
• Active alcohol or drug abuse and/or history of opioid abuse.
• Subjects receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine).
• Subjects with evidence of clinically significant gastrointestinal disease (e.g. paralytic ileus, peritoneal 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.
• Subjects who have a confirmed diagnosis of ongoing irritable bowel syndrome.
• Subjects suffering from diarrhea and/or opioid withdrawal.

Sponsors & Collaborators

• Mundipharma Research GmbH & Co KG: lead

Study Sites (1)

Dr S Ahmedzai

Sheffield, United Kingdom

Location

Related Publications (2)

• Koopmans G, Simpson K, De Andres J, Lux EA, Wagemans M, Van Megen Y. Fixed ratio (2:1) prolonged-release oxycodone/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives. Curr Med Res Opin. 2014 Nov;30(11):2389-96. doi: 10.1185/03007995.2014.971355. Epub 2014 Oct 13.

  PMID: 25265132 DERIVED

• Ahmedzai SH, Nauck F, Bar-Sela G, Bosse B, Leyendecker P, Hopp M. A randomized, double-blind, active-controlled, double-dummy, parallel-group study to determine the safety and efficacy of oxycodone/naloxone prolonged-release tablets in patients with moderate/severe, chronic cancer pain. Palliat Med. 2012 Jan;26(1):50-60. doi: 10.1177/0269216311418869. Epub 2011 Sep 21.

  PMID: 21937568 DERIVED

Related Links

• Results available on website

MeSH Terms

Conditions

Neoplasms; Pain; Constipation; Bronchiolitis Obliterans Syndrome

Interventions

Oxycodone; Naloxone

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Sam Ahmedzai

  University of Sheffield

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2007
• First Posted: August 9, 2007
• Study Start: September 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: June 1, 2010
• Last Updated: October 23, 2018

Record last verified: 2012-08

Locations

GB (1)