TL;DR
Turn your wind-down time into listening time
- Thousands of audiobooks, podcasts and originals
- Listen on your phone, tablet or Echo — also offline
- Cancel anytime
In a phase III trial of 351 adults with acute bipolar I mania, lumateperone improved mania scores compared with placebo, with a difference reported by day 3 and maintained through the study. The drug is not approved for manic episodes; the trial was presented at the NEI Fall Congress, and further details on its regulatory path were not reported.
A phase III trial of lumateperone found that the drug reduced acute mania symptoms in adults with bipolar I disorder more than placebo, with a statistically significant difference appearing by day 3 and continuing through day 22. The findings, presented at the Neuroscience Education Institute Fall Congress on November 6, add evidence for a potential treatment use that is not currently approved.
The double-blind study randomized 351 adults with an acute manic episode, with or without mixed features, to receive oral lumateperone 42 mg or placebo once daily for three weeks. Patients began treatment in hospital and could move to outpatient care after week two. The study population had severe mania at baseline, as measured by the Young Mania Rating Scale (YMRS).
By day 22, the lumateperone group had a greater reduction in YMRS total score than the placebo group. The least-squares mean difference was -3.7 points (95% confidence interval -5.61 to -1.86; P<0.0001). Researchers reported a significant separation from placebo by day 3, with the difference maintained from week one onward. Lumateperone also outperformed placebo on the key secondary measure of overall illness severity, the Clinical Global Impression-Severity score, with a least-squares mean difference of -0.4 (95% CI -0.58 to -0.17; P=0.0003).
Response, defined as at least a 50% reduction in YMRS score, occurred in 43.9% of participants receiving lumateperone and 23.7% receiving placebo. Remission, defined as a YMRS score of 12 or lower, was reported in 25.4% and 16.4%, respectively. These outcomes describe group results from this trial; they do not establish how an individual patient will respond.
A Potential Option for Acute Mania
Bipolar mania can involve severe symptoms and may require urgent clinical care. A treatment that shows improvement within days could be relevant to clinicians weighing how to manage an acute episode, particularly when symptom control is needed promptly. However, this trial compared lumateperone with placebo; it does not establish that the drug works faster or better than existing active treatments.
The reported response and remission differences give a fuller picture than the average score change alone. Roger S. McIntyre, the study’s presenting investigator, told MedPage Today that the response-rate results corresponded to a number needed to treat of 5. That figure is an interpretation of this study’s results, not a guarantee that treating five patients will produce a particular outcome in every clinical setting.
Approval status matters for patients and prescribers: lumateperone is authorized for other conditions, but not for manic episodes associated with bipolar I disorder. The findings may inform further review of the drug’s role, but they do not change its approved uses.
Popular right now
Sony WH-1000XM4 Wireless Noise Cancelling Headphones, Black
Dreame L50 Ultra Robot Vacuum and Mop Combo
Ninja Foodi DZ550 10-Qt DualZone Smart XL Air Fryer, 6-in-1, Black
As an affiliate, we earn on qualifying purchases.
How This Trial Fits Existing Evidence
Lumateperone, marketed as Caplyta, is an oral atypical antipsychotic taken once daily. According to the source report, it is approved for adults with bipolar depression, either alone or with lithium or valproate, for schizophrenia, and as an add-on to antidepressants for major depressive disorder. Its mechanism is not fully known; possible activity involving serotonin 5-HT2A and dopamine D2 receptors has been proposed.
This is the second pivotal phase III study reported for acute bipolar mania. The source says an identically designed sister trial was presented in September at Psych Congress and that the new results replicate and reinforce those findings. The current trial included patients with and without mixed features, meaning manic or hypomanic symptoms occurring alongside depressive symptoms. About one-third of participants had mixed features, and roughly 44% had experienced five or more lifetime manic episodes.
Participants were followed for three weeks, with treatment initially provided in an inpatient setting. The study’s timeframe therefore provides evidence about short-term outcomes during an acute episode, not long-term prevention of relapse or maintenance treatment.
“The overall clinical meaningfulness was not only observed rapidly on day 3, which was the second day post-treatment, but also response rates that translate into a number needed to treat of 5, indicating clinical relevance.”
— Roger S. McIntyre, MD, University of Toronto, speaking to MedPage Today
Limits of the Current Results
The report describes a three-week trial but does not provide longer-term results, such as whether improvement persists after treatment ends or affects future episodes. It also does not establish comparative effectiveness against other medicines used for acute mania. The study’s results are group averages and response rates, not a prediction of an individual patient’s outcome.
Adverse events were reported, including dizziness (10.4% versus 1.7%), dry mouth (5.8% versus 1.1%), and somnolence (5.2% versus 1.7%) with lumateperone versus placebo. Discontinuation because of adverse events was 4.0% with lumateperone and 3.4% with placebo. The source report does not provide a full account of all safety outcomes or subgroup results. It also does not specify whether a regulatory submission for the mania indication is planned or when one might occur.
Regulatory and Longer-Term Questions
The immediate next step is broader scrutiny of the phase III findings, including how they compare with the sister trial and the existing evidence for treatments used in acute mania. The source report did not announce a regulatory filing, a decision date, or a change to lumateperone’s approved indications. Any future approval would require review by the relevant regulator.
Further data would help clarify the durability of symptom improvement, safety with longer use, and how the medicine performs relative to active treatments. Until such information or a regulatory update is available, the reported results support a potential role for lumateperone under study, not an approved indication for bipolar mania.
Key Questions
What did the phase III trial find?
Lumateperone reduced mania scores more than placebo among 351 adults with acute bipolar I mania. The difference on the Young Mania Rating Scale was statistically significant by day 3 and remained through day 22.
Is lumateperone approved to treat bipolar mania?
No. The source report says lumateperone is approved for other conditions, including bipolar depression, but is not currently approved for manic episodes associated with bipolar I disorder.
How quickly did the trial report improvement?
Researchers reported a statistically significant difference from placebo by day 3. The study lasted three weeks, and the reported difference continued from week one through day 22.
What side effects were reported most often?
The most common reported treatment-emergent events with lumateperone were dizziness, dry mouth, and somnolence. The report gave rates of 10.4%, 5.8%, and 5.2%, respectively, compared with 1.7%, 1.1%, and 1.7% with placebo.
Does this study show lumateperone is better than other mania treatments?
No. The trial compared lumateperone with placebo, not with another active treatment. It also covered only three weeks, so longer-term outcomes and comparative effectiveness remain unanswered.
Source: medpagetoday.com
