Study 1 was a multicenter, randomized, double-blind active control clinical trial of 635 patients set to receive moderately emetogenic cancer chemotherapy. A single oral dose of 0.25 mg, 0.5 mg, or 0.75 mg ALOXI capsules given one hour prior to chemotherapy was compared to a single intravenous dose of 0.25 mg palonosetron HCl given 30 minutes prior to chemotherapy. Patients were randomized to either dexamethasone or placebo in addition to their assigned treatment. The majority of patients in the study were women (73%), white (69%), and naïve to previous chemotherapy (59%). The primary efficacy endpoint was Complete Response (no emetic episodes and no rescue medication) assessed in the acute phase (0 to 24 hours). A key secondary efficacy endpoint was Complete Response assessed in the delayed phase (24 to 120 hours). Other secondary endpoints included Complete Response for the acute plus delayed phases (0-120 hours) and “no nausea” for the acute and delayed phases.

Efficacy was based on demonstrating non-inferiority of oral palonosetron doses compared to the approved intravenous product. Non-inferiority criteria were met if the lower bound of the two-sided 98.3% confidence interval for the difference in complete response rates of oral palonosetron dose minus approved intravenous product was larger than -15%. The non-inferiority margin was 15%.

Efficacy Results

As shown in Table 2, ALOXI capsules 0.5 mg demonstrated non- inferiority to the active comparator during the 0 to 24 hour time interval; however, for the 24 to 120 hour time period, non-inferiority was not shown. The additional two oral palonosetron dose levels showed similar results.

Table 2: Proportion of Patients Achieving Complete Response Post- Chemotherapy

* To adjust for multiplicity of treatment groups, a lower-bound of a two-sided 98.3% confidence interval was used to compare to -15%, the negative value of the non-inferiority margin.

As indicated in the data above, analysis of the key secondary endpoint showed that a single dose of ALOXI capsules 0.5 mg was numerically similar to a single dose of intravenous palonosetron HCl 0.25 mg, however, statistical non-inferiority was not demonstrated. For ALOXI capsules 0.5 mg versus intravenous palonosetron HCl 0.25 mg, the proportion of patients with complete response in the acute plus delayed phase (0 to 120 hours) was 58.8% versus 59.3%, respectively. The proportions of patients with no nausea in the acute phase (0 to 24 hours) and delayed phase (24 to 120 hours) were also numerically similar between oral and intravenous doses.

Study 2 was a multicenter, open label, repeat cycle study performed to evaluate the safety and efficacy of single dose oral ALOXI capsules 0.75 mg in cancer patients receiving moderately emetogenic chemotherapy. An ALOXI capsule was given to 217 cancer patients in 654 chemotherapy cycles one hour before the start of chemotherapy. Approximately 74% of patients also received single dose oral or intravenous dexamethasone 30 minutes before chemotherapy. Complete Response was not formally evaluated for the repeat cycle application. However, in general, the antiemetic effect for the 0 to 24 hour interval was similar throughout the consecutively repeated cycles.