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LB-102

Schizophrenia

Regulatory submission
Not announced
Launch
Not announced
Last updated
345 sources

Product information and disease descriptionProduct descriptionProduct information

Contraindications/Warnings/Precautions/Adverse effects

17 evidence topics · 10 sources

Warnings and precautions
FDA-approved prescribing information, contraindications, boxed warning, and REMS

“We currently have no products approved for commercial sale or for which regulatory approval to market has been sought.” (opens the source at this quote in a new tab)

Risks described to NOVA-1 investigators

“Administration of second generation antipsychotics (SGAs) (including the metabolite of LB-102, amisulpride) can result in extrapyramidal symptoms, weight gain, elevations in lipids and blood sugar, sedation, dry mouth, constipation, dizziness, and falls due to low blood pressure, QTcF prolongation, cognitive impairment, and prolactin elevation.” (opens the source at this quote in a new tab)

“The effect of LB-102 on pregnant women and fetal development is unknown.” (opens the source at this quote in a new tab)

NOVA-1: adverse events by dose
Outcome, No. (%)LB-102 50 mg (n = 107)LB-102 75 mg (n = 108)LB-102 100 mg (n = 36)Placebo (n = 108)
Any TEAE“74 (69.2)”“62 (57.4)”“27 (75.0)”“60 (55.6)”
Any treatment-related TEAE“49 (45.8)”“34 (31.5)”“17 (47.2)”“23 (21.3)”
Any serious TEAE“1 (0.9)”“1 (0.9)”“1 (2.8)”“2 (1.9)”
TEAE leading to early withdrawal“2 (1.9)”“3 (2.8)”“3 (8.3)”“2 (1.9)”
Insomnia“27 (25.2)”“23 (21.3)”“14 (38.9)”“24 (22.2)”
Weight (increase)“13 (12.1)”“8 (7.4)”“3 (8.3)”“4 (3.7)”
Blood prolactin (increase)“7 (6.5)”“6 (5.6)”“3 (8.3)”“0”
Hyperprolactinemia“4 (3.7)”“2 (1.9)”“3 (8.3)”“0”
Somnolence“1 (0.9)”“4 (3.7)”“2 (5.6)”“0”
Blood creatine phosphokinase (increase)“4 (3.7)”“1 (0.9)”“2 (5.6)”“3 (2.8)”
Alanine aminotransferase (increase)“3 (2.8)”“1 (0.9)”“2 (5.6)”“1 (0.9)”
Constipation“4 (3.7)”“1 (0.9)”“2 (5.6)”“0”
NOVA-1: extrapyramidal symptoms, dystonia, and akathisia

“Extrapyramidal symptom incidence was low across all groups (placebo, 2 [1.9%]; LB-102 50 mg, 0 [0%]; 75 mg, 1 [0.9%]; 100 mg, 1 [2.8%]), as was dystonia (placebo, 1 [0.9%]; LB-102 50 mg, 0 [0%]; 75 mg, 3 [2.8%]; 100 mg, 1 [2.8%]).” (opens the source at this quote in a new tab)

“Evaluation of the SAS, BARS, and AIMS demonstrated values that remained stable over time, with little to no emergence of any antipsychotic-induced parkinsonism, akathisia, tardive dyskinesia, or other involuntary motor AEs.” (opens the source at this quote in a new tab)

“Severe TEAEs were reported in 5 participants (1.4%), including dystonia (75 mg, n = 1), psychotic disorder (100 mg, n = 1), schizophrenia (placebo, n = 2), and death (placebo, n = 1).” (opens the source at this quote in a new tab)

Preferred termLB-102 50 mg (N=107)LB-102 75 mg (N=108)LB-102 100 mg (N=36)Placebo (N=108)
Dystonia“0”“3 (2.8%)”“1 (2.8%)”“1 (0.9%)”
Akathisia“1 (0.9%)”“2 (1.8%)”“0”“1 (0.9%)”
Extrapyramidal disorder“0”“1 (0.9%)”“1 (2.8%)”“2 (1.9%)”
Total EPS“1 (1.0%)”“6 (5.6%)”“2 (5.6%)”“4 (3.7%)”

“one SAE in the 75 mg cohort (dystonia – deemed possibly related to treatment)” (opens the source at this quote in a new tab)

NOVA-1: hyperprolactinemia and prolactin-related adverse events

“Clinical AEs related to prolactin increase were reported in 5 participants, including galactorrhea (50 mg, n = 2; 75 mg, n = 1), breast enlargement (100 mg, n = 1), and erectile dysfunction (100 mg, n = 1).” (opens the source at this quote in a new tab)

“Elevated prolactin was reported from 6.5% of those receiving LB-102 50 mg to 8.3% of those receiving LB-102 100 mg; by comparison, data for amisulpride indicate significantly higher rates of hyperprolactinemia (25%-100%).” (opens the source at this quote in a new tab)

ParameterLB-102 50 mg (n = 107)LB-102 75 mg (n = 108)LB-102 100 mg (n = 36)Placebo (n = 108)
Prolactin, mean (SD) change from baseline to day 28, ng/mL“59.9 (55.11)”“51.4 (52.02)”“51.2 (48.07)”“1.3 (6.03)”
Adverse eventLB-102 50 mg (N=107)LB-102 75 mg (N=108)LB-102 100 mg (N=36)Placebo (N=108)
Hyperprolactinemia“11 (10.3%)”“8 (7.4%)”“6 (16.7%)”“0”
Galactorrhea“2 (1.9%)”“1 (0.9%)”“0”“0”
Breast enlargement“0”“0”“1 (2.8%)”“0”
Erectile dysfunction“0”“0”“1 (2.8%)”“0”
Total related to prolactin“2 (1.9%)”“1 (0.9%)”“2 (5.6%)”“0”
NOVA-1: QTc interval

“There were no clinically meaningful changes in blood pressure, pulse rate, or body temperature from baseline to day 28, and no notable shifts observed in QTcF (Fridericia-corrected QT interval) values” (opens the source at this quote in a new tab)

“An increase in QTcF to >500 msec for male and female patients.” (opens the source at this quote in a new tab)

“An increase in QTcF of >60 msec over Baseline.” (opens the source at this quote in a new tab)

“QTc Prolongation Minimal QT prolongation (4.3-5.4 ms); no patients met pre-specified stopping criteria” (opens the source at this quote in a new tab)

NOVA-1: weight gain and metabolic parameters

“Weight increase was the only TEAE to occur in 5% or more of the total population at a rate at least twice that observed with placebo but was not dose-dependent (placebo, 4 [3.7%], mean increase, 2.1 kg; 50 mg, 13 [12.1%], mean increase, 4.3 kg; 75 mg, 8 [7.4%], mean increase, 3.3 kg; 100 mg, 3 [8.3%], mean increase, 2.9 kg).” (opens the source at this quote in a new tab)

“A 7% or greater weight increase, using a last-observation-carried-forward approach, was reported by 61 participants (placebo, 11 [10.4%], mean increase, 6.9 kg; 50 mg, 27 [25.7%], mean increase, 8.2 kg; 75 mg, 20 [18.7%], mean increase, 7.2 kg; 100 mg, 3 [8.8%], mean increase, 7.2 kg)” (opens the source at this quote in a new tab)

“Site-level smoking restrictions and limited opportunity for physical activity, combined with minimal dietary or food restrictions, may have contributed to weight gain, limiting the ability to fully assess the metabolic profile of LB-102 under real-world outpatient conditions.” (opens the source at this quote in a new tab)

Parameter, mean (SD) change from baseline to day 28LB-102 50 mg (n = 107)LB-102 75 mg (n = 108)LB-102 100 mg (n = 36)Placebo (n = 108)
Weight, kg“4.3 (3.2)”“3.3 (2.8)”“2.9 (2.5)”“2.0 (2.9)”
Fasting glucose, mg/dL“2.3 (24.52)”“2.0 (13.62)”“7.0 (19.39)”“0.2 (12.07)”
Total cholesterol, mg/dL“7.7 (24.75)”“5.4 (23.98)”“5.8 (25.52)”“0.8 (25.06)”

“Over the course of the trial, we observed approximately 1.6 kg placebo-adjusted weight gain on a last observation carried forward basis.” (opens the source at this quote in a new tab)

“Despite the weight gain observed in the four-week trial, no clinically meaningful signal in metabolic parameters such as cholesterol, LDL, HDL, triglycerides or fasting glucose were observed.” (opens the source at this quote in a new tab)

NOVA-1: sedation, somnolence, and insomnia

“Across 251 dosed subjects, only one case of sedation was reported.” (opens the source at this quote in a new tab)

“TEAEs were generally balanced across treatment arms, except insomnia (more frequent with 75 mg) and weight increase.” (opens the source at this quote in a new tab)

“Common baseline comorbidities (ie, insomnia, anxiety, headache, and agitation) were among the most common TEAEs, suggesting that some TEAEs may represent the re-emergence, exacerbation, or fluctuation of preexisting symptoms rather than new, drug-related effects.” (opens the source at this quote in a new tab)

NOVA-1: orthostasis, suicidal ideation, and discontinuations

“there were no reports of orthostasis among patients treated with LB-102 in the trial” (opens the source at this quote in a new tab)

“one SAE in the 50 mg cohort (suicidal ideation – deemed possibly related to treatment)” (opens the source at this quote in a new tab)

“Other discontinuation-related TEAEs included psychotic disorder, suicidal ideation, alanine aminotransferase increase, lipase increase, toothache, COVID-19, and dystonia.” (opens the source at this quote in a new tab)

Phase 1: dose-limiting acute dystonia and maximum tolerated dose

“As a result of two cases of EPS (acute dystonia) at 200 mg in the MAD portion of the study, dosing of that arm was discontinued and doses for the remaining cohort were decreased to 150 mg/day.” (opens the source at this quote in a new tab)

“There were four instances of EPS (acute dystonia), typically associated with dopamine receptor occupancy in excess of 80%, one at 100 mg QD, one at 75 mg BID, and two at 100 mg BID.” (opens the source at this quote in a new tab)

“4 cases of moderate dystonia (200 mg QD, N = 1; 100 mg BID, N = 2; 75 mg BID, N = 1)” (opens the source at this quote in a new tab)

“Due to 2 TEAEs in the same SOC (acute dystonic reaction), treatment was halted in all healthy volunteers taking 100 mg LB-102 BID (Cohort 7) and the 2 healthy volunteers in Cohort 7 taking placebo.” (opens the source at this quote in a new tab)

“The MTD of LB-102 was identified as 150 mg per day as either 150 mg QD or 75 mg BID.” (opens the source at this quote in a new tab)

“At 50 mg and 100 mg QD, two of the doses evaluated in our Phase 2 trial (and the doses being evaluated in our Phase 3 trial) we observed no adverse events associated with QT prolongation, sedation, weight gain or EPS in our Phase 1 trial.” (opens the source at this quote in a new tab)

PET study: tolerability at 50 mg to 100 mg

“No episodes of acute dystonia were reported or observed, consistent with a prior study in healthy adults in which acute EPS was observed at higher doses of LB-102 (75 mg twice daily i.e. 150 mg/day).” (opens the source at this quote in a new tab)

Duration of controlled safety exposure

“The NOVA 1 trial was conducted over 4 weeks and was not designed to evaluate the long-term durability of treatment.” (opens the source at this quote in a new tab)

Class context: U.S. boxed warning on antipsychotic use in elderly patients with dementia-related psychosis

“WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS” (opens the source at this quote in a new tab)

“Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.” (opens the source at this quote in a new tab)

“Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients.” (opens the source at this quote in a new tab)

“Amisulpride is not licensed for the treatment of dementia-related behavioural disturbances.” (opens the source at this quote in a new tab)

Class context: amisulpride labeling on QT prolongation

“BARHEMSYS causes dose- and concentration-dependent prolongation of the QT interval” (opens the source at this quote in a new tab)

“Avoid use in patients with congenital long QT syndrome and in patients taking droperidol.” (opens the source at this quote in a new tab)

“In 40 healthy Caucasian and Japanese subjects, the maximum mean difference (95% upper confidence bound) in QTcF from placebo after baseline-correction (ΔΔQTcF) was 5.0 (7.1) milliseconds after a 2-minute intravenous infusion of 5 mg BARHEMSYS and 23.4 (25.5) milliseconds after an 8- minute intravenous infusion of 40 mg BARHEMSYS” (opens the source at this quote in a new tab)

“Caution should be exercised when amisulpride is prescribed in patients with known cardiovascular disease or family history of QT prolongation and concomitant use with neuroleptics should be avoided.” (opens the source at this quote in a new tab)

“Amisulpride has been associated with QT prolongation.” (opens the source at this quote in a new tab)

“amisulpride is a weak inhibitor of human ether-a-go-go-related gene (hERG) potassium channels, and it has been shown that QT prolongation is dependent on amisulpride systemic exposure” (opens the source at this quote in a new tab)

“pharmacovigilance data on amisulpride from the United Kingdom covering 16,000 patient exposure years had 8 incidences of QT prolongation with all 8 events occurring in patients concurrently taking clozapine, a drug known to prolong the QT interval” (opens the source at this quote in a new tab)

“At therapeutic doses of amisulpride up to 1,200 mg/day, literature reports of cardiac toxicity due to QT prolongation are extremely rare.” (opens the source at this quote in a new tab)

Class context: amisulpride labeling on hyperprolactinemia

“Amisulpride causes an increase prolactin levels.” (opens the source at this quote in a new tab)

“Cases of benign pituitary tumours such as prolactinoma have been observed during Amisulpride therapy (see section 4.8).” (opens the source at this quote in a new tab)

“In case of very high levels of prolactin or clinical signs of pituitary tumour (such as visual field defect and headache), pituitary imaging should be performed.” (opens the source at this quote in a new tab)

“Serum prolactin concentrations were measured in Study 1 where 5% (9/176) of BARHEMSYS-treated patients vs 1% (1/166) of placebo-treated patients had increased blood prolactin reported as an adverse reaction.” (opens the source at this quote in a new tab)

Class context: contraindications in oral amisulpride labeling
ContraindicationQuoted text
Hypersensitivity“Hypersensitivity to the active substance or to other ingredients of the medicinal product.”
Prolactin-dependent tumours“Concomitant prolactin-dependent tumours e.g. pituitary gland prolactinomas or breast cancer (see sections 4.4 and 4.8)”
Phaeochromocytoma“Phaeochromocytoma”
Children“Children up to puberty”
Levodopa“Combination with levodopa (see section 4.5)”
Class context: other warnings in oral amisulpride labeling

“As with other neuroleptics, neuroleptic malignant syndrome (NMS) may occur.” (opens the source at this quote in a new tab)

“Amisulpride may lower the seizure threshold.” (opens the source at this quote in a new tab)

“Severe liver toxicity has been reported with amisulpride use.” (opens the source at this quote in a new tab)

“Therefore, gradual withdrawal of amisulpride is advisable.” (opens the source at this quote in a new tab)

Safety beyond 4 weeks of treatment, tardive dyskinesia, and neuroleptic malignant syndrome with LB-102

No evidence found.