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

Sam H Ahmedzai, Friedemann Nauck, Gil Bar-Sela, Björn Bosse, Petra Leyendecker, Michael Hopp, Sam H Ahmedzai, Friedemann Nauck, Gil Bar-Sela, Björn Bosse, Petra Leyendecker, Michael Hopp

Abstract

Objective: An examination of whether oxycodone/naloxone prolonged-release tablets (OXN PR) can improve constipation and maintain analgesia, compared with oxycodone prolonged-release tablets (OxyPR) in patients with moderate/severe cancer pain.

Methods: Randomized, double-blind, active-controlled, double-dummy, parallel-group study in which 185 patients were randomized to receive up to 120 mg/day of OXN PR or OxyPR over 4 weeks. Efficacy assessments included Bowel Function Index (BFI), Brief Pain Inventory Short-Form (BPI-SF), laxative and rescue medication use. Quality of life (QoL) and safety assessments were conducted.

Results: After 4 weeks, mean BFI score was significantly lower with OXN PR; mean total laxative intake was 20% lower with OXN PR. Mean BPI-SF scores were similar for both treatments and the average rate of analgesic rescue medication use was low and comparable. QoL assessments were stable and comparable with greater improvements in constipation-specific QoL assessments with OXN PR. Overall, rates of adverse drug reactions were similar.

Conclusions: OXN PR provides superior bowel function in cancer pain patients, compared with OxyPR, without compromising analgesic efficacy or safety. This study confirms that OXN PR is well tolerated and efficacious in cancer pain patients and results are in line with those seen in non-malignant pain patients.

Trial registration: ClinicalTrials.gov NCT00513656.

Figures

Figure 1.
Figure 1.
(a) Patient disposition; (b) study populations. The double-blind safety population included all patients who received any dose of study medication; the full-analysis population I excluded one patient from the double-blind safety population who did not receive treatment and was hence not included in the analysis; the full-analysis population II excluded those patients from the original full-analysis population who discontinued due to AEs other than constipation or lack of efficacy within the first 14 days (in order to obtain reliable BFI values and prevent possible skewing due to these early withdrawals); the per-protocol population included patients who received at least one dose of study medication during the double-blind phase and who sufficiently complied with the study protocol. OXN PR: oxycodone/naloxone prolonged-release tablets, OxyPR: oxycodone prolonged-release tablets, AE: adverse event, BFI: Bowel Function Index.
Figure 2.
Figure 2.
Effect of OXN PR and OxyPR treatment on (a) mean (± standard error) BFI score (full analysis population II, LOCF); and (b) mean (± standard error) BPI-SF score (per-protocol population, LOCF), by study day. aPopulations varied at each day. Error bars represent standard error; OXN bp-value and confidence interval for treatment difference adjusted for baseline using an ANCOVA model. (a) BFI: 95% CI −19.03 to −3.24; (b) BPI-SF: 90% CI −0.47 to −0.45. OXN PR: oxycodone/naloxone prolonged-release tablets, OxyPR: oxycodone prolonged-release tablets, BFI: bowel function index. (Copyright for the BFI is owned by Mundipharma Research, 2002; the BFI is the subject of European Patent Application Publication No. EP 1 860 988 and corresponding patents and applications in other countries).

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