Targeting muscarinic receptors for treating schizophrenia.

In all three studies, the primary endpoint was achieved, with a highly significant reduction in PANSS total score from baseline to endpoint (p < 0.0001).

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Although there was a numerical separation on the PANSS total score between the emraclidine and placebo arms, the differences did not reach statistical significance.

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Although the study did not meet its primary endpoint (least-squares [LS] mean change in PANSS total score at Week 6: −14.3 vs −12.2 for placebo; LS mean difference −2.0, 95 % CI –4.5 to 0.5; p = 0.11), post hoc subgroup analyses revealed a nominally significant benefit among patients receiving non-risperidone background therapy (n ̃ 130), with a mean PANSS reduction of −15.1 for COBENFY versus −11.7 for placebo (LS mean difference −3.4; 95 % CI –6.3 to −0.5; p ≈ 0.03) [ 106 ].

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