The efficacy of asenapine sublingual tablets in the treatment of schizophrenia in adults was evaluated in three fixed-dose, short-term (6 week), randomized, double-blind, placebo-controlled, and active-controlled (haloperidol, risperidone, and olanzapine) trials of adult patients who met DSM-IV criteria for schizophrenia and were having an acute exacerbation of their schizophrenic illness. In two of the three trials asenapine sublingual tablets demonstrated superior efficacy to placebo. In a third trial, asenapine sublingual tablets could not be distinguished from placebo; however, an active control in that trial was superior to placebo.

In the two positive trials for asenapine sublingual tablets, the primary efficacy rating scale was the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30 item scale that measures positive symptoms of schizophrenia (7 items), negative symptoms of schizophrenia (7 items), and general psychopathology (16 items), each rated on a scale of 1 (absent) to 7 (extreme); total PANSS scores range from 30 to 210. The primary endpoint was change from baseline to endpoint on the PANSS total score. The results of the asenapine sublingual tablets trials in schizophrenia follow:

In trial 1, a 6-week trial (n=174), comparing asenapine sublingual tablets (5 mg twice daily) to placebo, asenapine sublingual tablets 5 mg twice daily was statistically superior to placebo on the PANSS total score (Trial 1 in Table 13).

In trial 2, a 6-week trial (n=448), comparing two fixed doses of asenapine sublingual tablets (5 mg and 10 mg twice daily) to placebo, asenapine sublingual tablets 5 mg twice daily was statistically superior to placebo on the PANSS total score. Asenapine sublingual tablets 10 mg twice daily showed no added benefit compared to 5 mg twice daily and was not significantly different from placebo (Trial 2 in Table 13).

An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age, sex or race.

Maintenance of efficacy has been demonstrated in a placebo-controlled, double-blind, multicenter, flexible dose (5 mg or 10 mg twice daily based on tolerability) clinical trial with a randomized withdrawal design. All patients were initially administered 5 mg twice daily for 1 week and then titrated up to 10 mg twice daily. A total of 700 patients entered open-label treatment with asenapine sublingual tablets for a period of 26 weeks. Of these, a total of 386 patients who met pre-specified criteria for continued stability (mean length of stabilization was 22 weeks) were randomized to a double-blind, placebo-controlled, randomized withdrawal phase. Asenapine sublingual tablets was statistically superior to placebo in time to relapse or impending relapse defined as increase in PANSS ≥20% from baseline and a Clinical Global Impression–Severity of Illness (CGI-S) score ≥4 (at least 2 days within 1 week) or PANSS score ≥5 on "hostility" or "uncooperativeness" items and CGI-S score ≥4 (≥2 days within a week), or PANSS score ≥5 on any two of the following items: "unusual thought content," "conceptual disorganization," or "hallucinatory behavior" items, and CGI-S score ≥4 (≥2 days within 1 week) or investigator judgment of worsening symptoms or increased risk of violence to self (including suicide) or other persons. The Kaplan-Meier curves of the time to relapse or impending relapse during the double-blind, placebo-controlled, randomized withdrawal phase of this trial for asenapine sublingual tablets and placebo are shown in Figure 4.

Figure 4: Kaplan-Meier Estimation of Percent Relapse/Impending Relapse for Asenapine Sublingual Tablets and placebo