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In this study - a randomized, double-blind, placebo-controlled clinicaltrial - patients were assigned to four weeks of treatment with either Lilly'sinvestigational compound LY2140023; olanzapine, an atypical antipsychoticmedication that targets dopamine and serotonin receptors as an active control;or placebo. The study demonstrated that:
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"These data provide compelling new evidence that mGlu2/3 receptor agonistshave antipsychotic properties and may provide a completely new therapeuticapproach for treating schizophrenia and, perhaps, other neuropsychiatricdisorders," said Steven Paul, M.D., Lilly's executive vice president ofscience and technology. "Additional and longer-term studies are needed toconfirm and extend these exciting initial findings. However, these datasuggest that LY2140023 may provide a new alternative for the treatment of thisoften devastating condition."
Study Design
The trial was a proof of concept study designed to determine LY2140023superiority versus placebo. Olanzapine was used as an active control. 196patients with schizophrenia were randomly assigned to LY2140023 (40 mg twicedaily), olanzapine (15 mg daily) or placebo. All participants werehospitalized to ensure patient safety, tapered off from any pre-trialantipsychotic medications (no therapeutically stable patients were included inthe trial), and treated in a double-blind manner for four weeks. In all, 118patients completed four weeks of the planned study treatment.
Results
Treatment with LY2140023 or olanzapine resulted in statisticallysignificant improvement in PANSS (Positive and Negative Syndrome Scale) totalscore (primary outcome) compared to placebo (-20.8, P < 0.001; -26.7, P <0.001; respectively), After four weeks of treatment, the study showed thatboth the LY2140023 group (32.0%, P < 0.001) and the olanzapine group (41.2%, P< 0.001) demonstrated significantly greater response rates compared to theplacebo group (3.2%). Response was measured primarily by the PANSS, the mostcommon scale used for measuring symptoms of patients with schizophrenia. Apatient showing a 25% or more decrease in PANSS total score was defined as aresponder. Additionally, a mean 0.51-kg weight reduction from baseline wasobserved in the LY2140023 group. A moderate but statistically significantweight gain was observed in the olanzapine group (0.74 kg, P = 0.017) relativeto the placebo group.
Results showed that the placebo arm experienced the highest rate of studydiscontinuation due to lack of efficacy, however, discontinuation due toadverse events was not significantly different across the three treatmentgroups (P = 0.66).
Adverse Events
Overall, the study showed that LY2140023 40mg, given twice daily, wasfound to be safe and well-tolerated, with most adverse events being mild tomoderate in severity and not treatment-limiting. The most common treatment-emergent adverse events in the LY2140023 group were insomnia, affect lability(P = 0.038), nausea, headache, somnolence and blood creatine phosphokinaseincrease. The adverse event profile of LY2140023 did not include prolactinincrease or worsening of extrapyramidal symptoms (EPS). Although moodlability seems to represent the most important potential adverse event, itshould be noted that this outcome was observed primarily at one clinical site.In the olanzapine group, treatment-emergent adverse events included elevationin blood triglyceride levels (P = 0.005), insomnia, weight gain (P = 0.034),somnolence, akathisia, agitation and periodontitis (P = 0.03).
About LY2140023
