According to the company, the primary analysis comparing XP19986 to placebo did not reach statistical significance. However, pre-defined subgroup analyses showed statistically significant benefits of XP19986 on a number of important parameters. XP19986 was generally well tolerated at all dose levels.
The randomized, parallel-group, double-blind, placebo-controlled Phase II clinical trial enrolled 156 subjects at 16 sites in the US. Enrolled subjects had reflux symptoms occurring at least three days a week and had either no history of taking proton pump inhibitors (PPIs) (PPI Naive) or a history of at least a partial symptom response to PPI therapy (PPI Experienced). Enrolled subjects discontinued prior therapy for gastroesophageal reflux disease (GERD) other than rescue antacids.
The primary efficacy analysis involved the difference in the change in total number of weekly heartburn episodes between the XP19986 dose groups and placebo through four weeks of treatment. Change in the total number of weekly heartburn episodes was analyzed using a repeated measures ANCOVA model. The primary efficacy analysis compared pooled XP19986 treatment groups (60mg dosed once a day and 30mg dosed twice a day; and 60mg and 40mg dosed once a day) with the placebo group and included both PPI Experienced and PPI Naive subjects. This analysis did not reach statistical significance.
The primary ANCOVA analysis indicated that the status of a subject as either PPI Naive or PPI Experienced had a significant impact on the outcome of the analysis (PPI history status by treatment group interaction term (p=0.02)).
A number of pre-defined secondary analyses were conducted on subjects in the PPI Experienced population who completed four weeks of treatment. All XP19986 dose groups showed a greater adjusted mean percent reduction from baseline at week four in weekly heartburn episodes that was statistically significant compared to placebo. XP19986 was generally well tolerated at all dose levels.
Ronald Barrett, XenoPort’s CEO, said: “While we are disappointed that statistical significance in the primary analysis of this trial was not met, we are pleased that the subgroup analyses showed that XP19986 monotherapy was effective in reducing heartburn in GERD subjects who have previously experienced at least a partial response to PPIs.
“We are particularly encouraged by the results indicating that XP19986 appears to have acceptable tolerability for the GERD patient population. Effective treatment for GERD patients who remain symptomatic despite PPI therapy represents an important unmet medical need.”