The α7 Nicotinic Agonist ABT-126 in the Treatment of Cognitive Impairment Associated with Schizophrenia in Nonsmokers: Results from a Randomized Controlled Phase 2b Study

Abstract

A double-blind, placebo-controlled, parallel-group, 24-week, multicenter trial was conducted to evaluate the efficacy and safety of 3 doses of ABT-126, an α7 nicotinic receptor agonist, for the treatment of cognitive impairment in nonsmoking subjects with schizophrenia. Clinically stable subjects were randomized in 2 stages: placebo, ABT-126 25 mg, 50 mg or 75 mg once daily (stage 1) and placebo or ABT-126 50 mg (stage 2). The primary analysis was the change from baseline to week 12 on the MATRICS Consensus Cognitive Battery (MCCB) neurocognitive composite score for ABT-126 50 mg vs placebo using a mixed-model for repeated-measures. A key secondary measure was the University of California Performance-based Assessment-Extended Range (UPSA-2ER). A total of 432 subjects were randomized and 80% (344/431) completed the study. No statistically significant differences were observed in either the change from baseline for the MCCB neurocognitive composite score (+2.66 [ ± 0.54] for ABT-126 50 mg vs +2.46 [ ± 0.56] for placebo at week 12; P40.05) or the UPSA-2ER. A trend for improvement was seen at week 24 on the 16-item Negative Symptom Assessment Scale total score for ABT-126 50 mg (change from baseline − 4.27 ± [0.58] vs − 3.00 ± [0.60] for placebo; P = 0.059). Other secondary analyses were generally consistent with the primary end point results. Adverse event rates were similar for ABT-126 and placebo. ABT-126 did not demonstrate a consistent effect on cognition in nonsmoking subjects with schizophrenia; however, a trend toward an effect was observed on negative symptoms. ClincalTrials.gov registration: NCT01655680.

A Randomized Clinical Trial of Oxytocin or Galantamine for the Treatment of Negative Symptoms and Cognitive Impairments in People With Schizophrenia

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Pharmacological Augmentation of Psychosocial and Remediation Training Efforts in Schizophrenia

“…There has been much a more substantial effort in the domain of α-7 receptor agonists; however, results have been inconsistent. Several different treatments have failed to show differences from placebo in studies on patients with schizophrenia ( 65 , 66 ). A short-term study of the α-7 receptor agonist DMXB-A found separation between active and placebo treatment in a cross-over design ( 67 ).…”

Metabolism and Disposition of a Novel Selective α7 Neuronal Acetylcholine Receptor Agonist ABT-126 in Humans: Characterization of the Major Roles for Flavin-Containing Monooxygenases and UDP-Glucuronosyl Transferase 1A4 and 2B10 in Catalysis

“…In another phase 2a trial in subjects with schizophrenia, ABT-126 demonstrated a precognitive effect in nonsmoking subjects, particularly in verbal learning, working memory, and attention (Haig et al, 2016b). A follow-up dose-ranging study showed that ABT-126 did not demonstrate a consistent effect on cognition in nonsmoking subjects with schizophrenia; however, a trend toward a therapeutic effect was observed on negative symptoms (Haig et al, 2016a).…”