Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain.

OBJECTIVE

To assess the safety and efficacy of adding intrathecal ziconotide to intrathecal morphine in patients being treated with a stable intrathecal morphine dose.

DESIGN

Phase II, multicenter, open-label study with a 5-week titration phase and an extension phase.

SETTING

Outpatient clinics.

PATIENTS

Patients with suboptimal pain relief receiving stable intrathecal morphine doses (2-20 mg/day).

INTERVENTIONS

Intrathecal morphine dosing remained constant during the titration phase. Ziconotide therapy began at 0.60 microg/day and was titrated to a maximum of 7.2 microg/day. During the extension phase, ziconotide and intrathecal morphine dosing were adjusted at the investigator's discretion.

OUTCOME MEASURES

Safety was assessed primarily via adverse event reports. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption.

RESULTS

Twenty-six patients were enrolled. Treatment-emergent adverse events were generally mild or moderate; the most common (> or = 15% of patients in either study phase) study drug-related (i.e., ziconotide/morphine combination [or ziconotide monotherapy in the extension phase only]) events were confusion, dizziness, abnormal gait, hallucinations, and anxiety. The mean percentage improvement in visual analog scale of pain intensity scores was 14.5% (95% confidence interval: -9.4% to 38.5%) from baseline to week 5 and varied during the extension phase (range: -0.4% to 42.8%). Mean percentage change from baseline in systemic opioid consumption was -14.3% at week 5 and varied considerably during the extension phase.

CONCLUSIONS

Ziconotide, combined with stable intrathecal morphine, may reduce pain and decrease systemic opioid use in patients with pain inadequately controlled by intrathecal morphine alone.