Page last updated: 2024-12-05

viloxazine

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Description

Viloxazine: A morpholine derivative used as an antidepressant. It is similar in action to IMIPRAMINE. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID5666
CHEMBL ID306700
CHEBI ID94405
SCHEMBL ID34168
MeSH IDM0022667

Synonyms (53)

Synonym
2-((2-ethoxyphenoxy)methyl)morpholine
morpholine, 2-[(2-ethoxyphenoxy)methyl]-
KBIO1_001019
DIVK1C_001019
2-(2-ethoxyphenoxymethyl)tetrahydro-1,4-oxazine
morpholine, 2-((2-ethoxyphenoxy)methyl)-
viloxazinum [inn-latin]
viloxazine [inn:ban]
viloxazina [inn-spanish]
einecs 256-281-7
ici-58,834
viloxazin
ccris 9180
OPREA1_394269
viloxazine
IDI1_001019
NINDS_001019
CHEMBL306700 ,
D08673
viloxazine (inn)
46817-91-8
2-[(2-ethoxyphenoxy)methyl]morpholine
2-(2-ethoxy-phenoxymethyl)-morpholine (viloxazine)
2-(2-ethoxy-phenoxymethyl)-morpholine
bdbm50025691
2-(2-ethoxy-phenoxymethyl)-morpholine(viloxazine)
AKOS013400287
unii-5i5y2789zf
viloxazinum
viloxazina
5i5y2789zf ,
BRD-A59198242-003-01-1
(+/-)-2-(o-ethoxyphenoxymethyl)morpholine
viloxazine [vandf]
viloxazine [who-dd]
viloxazine [mi]
viloxazine [inn]
SCHEMBL34168
2-(o-ethoxyphenoxymethyl)morpholine
2-[(o-ethoxyphenoxy)methyl]morpholine
DTXSID6057900 ,
DB09185
CHEBI:94405
Z1235945951
Q907148
gtpl11502
CS-0491105
HY-W380450
EN300-253642
dtxcid0031683
n06ax09
viloxazinum (inn-latin)
viloxazina (inn-spanish)

Research Excerpts

Overview

Viloxazine is a second generation antidepressant drug. It has a short apparent half-life (T1/2 elim: 2 to 5 h (3.4 h)

ExcerptReferenceRelevance
"Viloxazine is a second generation antidepressant drug with a short apparent half-life (T1/2 elim: 2 to 5 h (3.4 h), which requires once a day 3 h i.v."( [Clinical pharmacokinetics of viloxazine chlorhydrate. Practical implications].
Bouquet, S; Guibert, S; Lavoisy, J; Vandel, B,
)
1.14

Effects

ExcerptReferenceRelevance
"Viloxazine has a long history of clinical use in Europe as an antidepressant, and has recently been repurposed into an extended-release form for the treatment of attention-deficit/hyperactivity disorder in the USA. "( Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status.
Candler, SA; Findling, RL; Garcia-Olivares, J; Nasser, AF; Newcorn, JH; O'Neal, W; Schwabe, S; Yu, C, 2021
)
3.51
"Viloxazine has a long history of clinical use in Europe as an antidepressant, and has recently been repurposed into an extended-release form for the treatment of attention-deficit/hyperactivity disorder in the USA. "( Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status.
Candler, SA; Findling, RL; Garcia-Olivares, J; Nasser, AF; Newcorn, JH; O'Neal, W; Schwabe, S; Yu, C, 2021
)
3.51

Actions

ExcerptReferenceRelevance
"Viloxazine did not suppress the morphine and barbital withdrawal signs in monkeys that had been made physically dependent on these drugs and withdrawal."( Drug dependence potential of viloxazine hydrochloride tested in rhesus monkeys.
Kiyohara, H; Wakasa, Y; Yanagita, T, 1980
)
1.27

Treatment

ExcerptReferenceRelevance
"Treatment with viloxazine ER resulted in a statistically significant improvement in primary and key secondary endpoints, indicating improvements in attention-deficit/hyperactivity disorder symptomology, executive function, and overall clinical illness severity in adults. "( A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Efficacy and Safety of Viloxazine Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder.
Chaturvedi, SA; Childress, A; Cutler, AJ; Fry, N; Hull, JT; Kosheleff, AR; Liranso, T; Nasser, A; Odebo, O; Rubin, J; Schwabe, S, 2022
)
1.29

Toxicity

ExcerptReferenceRelevance
" Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical examinations, ECGs, and the Columbia-Suicide Severity Rating Scale."( A Phase III, Randomized, Placebo-controlled Trial to Assess the Efficacy and Safety of Once-daily SPN-812 (Viloxazine Extended-release) in the Treatment of Attention-deficit/Hyperactivity Disorder in School-age Children.
Adewole, T; Busse, GD; Chowdhry, F; Cutler, AJ; Findling, RL; Fry, N; Hull, JT; Jones, NJ; Liranso, T; Nasser, A; Schwabe, S, 2020
)
0.77
" The most common treatment-related adverse events that occurred in ≥5% of subjects receiving viloxazine ER were insomnia (14."( A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Efficacy and Safety of Viloxazine Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder.
Chaturvedi, SA; Childress, A; Cutler, AJ; Fry, N; Hull, JT; Kosheleff, AR; Liranso, T; Nasser, A; Odebo, O; Rubin, J; Schwabe, S, 2022
)
1.16

Pharmacokinetics

Viloxazine hydrochloride is an antidepressant drug with a half-life of 3-4 h in most subjects at low dosage. Its pharmacokinetic properties and tolerability make viloxazine ER a useful addition to the FDA approved ADHD treatments.

ExcerptReferenceRelevance
" The other pharmacokinetic parameters such as half-life, clearance and volume of distribution where the same irregardless of the administration route."( Effects of administration route on pharmacokinetics of viloxazine in the rabbit.
Bourin, M; Kergueris, MF; Larousse, C; Ortega, A; Thomare, P, 1992
)
0.53
"Pharmacokinetic data of an antidepressant agent: Apparent half-life (T1/2 elim), time of peak plasma concentration (Tmax), bioavailability, have a major contribution to determine optimal dosage in accordance with a low modification of steady-state levels."( [Clinical pharmacokinetics of viloxazine chlorhydrate. Practical implications].
Bouquet, S; Guibert, S; Lavoisy, J; Vandel, B,
)
0.42
"Animal and human studies have indicated that viloxazine hydrochloride, an antidepressant drug with a half-life of 3-4 h in most subjects at low dosage, is rapidly and almost completely absorbed after oral administration."( Comparative pharmacokinetic study of conventional and sustained-release viloxazine in normal volunteers.
Beneroso, N; Bourin, M; Kergueris, MF; Larousse, C; Normand, YL; Ribeyrol, M, 1989
)
0.77
" Pharmacokinetic studies in the mouse showed peak plasma levels to occur 30 min following oral doses, with a mean half-life of 58 min."( Anticonvulsant and proconvulsant properties of viloxazine hydrochloride: pharmacological and pharmacokinetic studies in rodents and the epileptic baboon.
Adam, HK; Anlezark, GM; Greenwood, DT; Meldrum, BS, 1982
)
0.52
"The pharmacokinetic characteristics of a new antidepressant, viloxazine hydrochloride, were investigated in five males and five females to study sex differences."( Pharmacokinetics of viloxazine hydrochloride in man.
Blum, D; Jounet, JM; Vandel, B; Vandel, S,
)
0.7
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35
" Viloxazine extended-release: Cmax = 95."( Pharmacokinetics of Coadministered Viloxazine Extended-Release (SPN-812) and Lisdexamfetamine in Healthy Adults.
Adewole, T; Faison, SL; Fry, N; Maletic, V; Nasser, A; Odebo, O; Wang, Z,
)
1.32
"Out of 27 enrolled subjects, 25 were included in the pharmacokinetic analysis."( Impact of a High-Fat Meal and Sprinkled Administration on the Bioavailability and Pharmacokinetics of Viloxazine Extended-Release Capsules (Qelbree
Adeojo, LW; Kosheleff, AR; Liranso, T; Nasser, A; Odebo, O; Schwabe, S; Wang, Z, 2022
)
0.94
" However, its pharmacokinetic properties and tolerability make viloxazine ER a useful addition to the collection of FDA approved ADHD treatments."( Evaluating the pharmacokinetics of extended release viloxazine in the treatment of children with attention-deficit/hyperactivity disorder.
Burton, S; Childress, A, 2022
)
1.21

Bioavailability

ExcerptReferenceRelevance
" The drug is very well absorbed orally, only 2% being found in faeces."( Blood level studies with viloxazine hydrochloride in man.
Bayliss, PF; Case, DE, 1975
)
0.56
" Known metabolites of viloxazine do not interfere with the analysis, and experience with several hundred samples in a bioavailability study demonstrated the applicability and reliability of the method."( High-pressure liquid chromatographic determination of viloxazine in human plasma and urine.
Gillilan, R; Mason, WD, 1981
)
0.83
" Relative bioavailability analyses were performed to assess the impact of each test condition against the control condition (intact capsule, fasting)."( Impact of a High-Fat Meal and Sprinkled Administration on the Bioavailability and Pharmacokinetics of Viloxazine Extended-Release Capsules (Qelbree
Adeojo, LW; Kosheleff, AR; Liranso, T; Nasser, A; Odebo, O; Schwabe, S; Wang, Z, 2022
)
0.94

Dosage Studied

Viloxazine levels in blood and CSF have been measured following acute and chronic dosing in depressed patients. The study raised some question as to the adequacies of the dosage utilized since there was an absence of any apparent side effects.

ExcerptRelevanceReference
" Dosage ranged from 50-225 mg daily, and treatment lasted from 2-26 weeks."( A review of controlled studies with nomifensine, performed outside the UK.
Habermann, W, 1977
)
0.26
" Repeated dosing at 4 hourly intervals leads to slightly higher blood levels after the second, but not subsequent, doses."( Blood level studies with viloxazine hydrochloride in man.
Bayliss, PF; Case, DE, 1975
)
0.56
"Pharmacokinetic data of an antidepressant agent: Apparent half-life (T1/2 elim), time of peak plasma concentration (Tmax), bioavailability, have a major contribution to determine optimal dosage in accordance with a low modification of steady-state levels."( [Clinical pharmacokinetics of viloxazine chlorhydrate. Practical implications].
Bouquet, S; Guibert, S; Lavoisy, J; Vandel, B,
)
0.42
" Our results suggest that the dosage of theophylline should be decreased and its plasma concentrations monitored when viloxazine is prescribed."( A study of the interaction of viloxazine with theophylline.
Bouquet, S; Griesemann, E; Lavoisy, J; Perault, MC; Vandel, B, 1989
)
0.77
" The antidepressant effects of the substance were independently recognized in seven uncontrolled clinical trials and verified in 11 published standard controlled clinical studies in which viloxazine in the dosage range from 150- to 300-mg dosage was equal in overall therapeutic efficacy to imipramine and amitriptyline, but produced a lower incidence of side effects."( Viloxazine: a review of the literature.
Ban, TA; McEvoy, JP; Wilson, WH, 1980
)
1.89
" There appeared to be no difference between the viloxazine-treated group and the placebo-treated group, although the study raised some question as to the adequacies of the dosage utilized since there was an absence of any apparent side effects."( Viloxazine and the depressed schizophrenic--methodological issues.
Kurland, AA; Nagaraju, A, 1981
)
1.96
" The first, of mild severity, was controlled with an increase in daily dosage of 100 mg."( [Long-term tolerance of viloxazine].
Brion, S; Chevalier, JF, 1982
)
0.57
"Viloxazine levels in blood and CSF have been measured following acute and chronic dosing in depressed patients."( Relationship between blood and cerebrospinal levels of the antidepressant agent viloxazine.
Adam, HK; Elwan, O, 1980
)
1.93
" for 10 days) on the steady-state plasma concentrations of Oxcarbazepine (OXC), its active metabolite 10, 11-dihydro-10-hydroxy-carbazepine (MHD) and the corresponding diol (DHD) were studied in a randomized, double-blind cross-over placebo-controlled trial in 6 epileptic patients stabilized on a fixed dosage of OXC."( Effects of the antidepressant drug viloxazine on oxcarbazepine and its hydroxylated metabolites in patients with epilepsy.
Artesi, C; Di Perri, R; Fazio, A; Oteri, G; Perucca, E; Pisani, F; Xiao, B, 1994
)
0.57
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
aromatic etherAny ether in which the oxygen is attached to at least one aryl substituent.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (3)

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Sodium-dependent noradrenaline transporter Homo sapiens (human)Kd0.15500.00080.25331.0600AID145563
Sodium-dependent serotonin transporterHomo sapiens (human)Kd17.30000.00010.03170.2000AID204080
Sodium-dependent dopamine transporter Homo sapiens (human)Kd0.15500.02502.14439.3000AID64372
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (55)

Processvia Protein(s)Taxonomy
monoamine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transportSodium-dependent noradrenaline transporter Homo sapiens (human)
chemical synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
response to xenobiotic stimulusSodium-dependent noradrenaline transporter Homo sapiens (human)
response to painSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine uptakeSodium-dependent noradrenaline transporter Homo sapiens (human)
neuron cellular homeostasisSodium-dependent noradrenaline transporter Homo sapiens (human)
amino acid transportSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine uptake involved in synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
sodium ion transmembrane transportSodium-dependent noradrenaline transporter Homo sapiens (human)
monoamine transportSodium-dependent serotonin transporterHomo sapiens (human)
response to hypoxiaSodium-dependent serotonin transporterHomo sapiens (human)
neurotransmitter transportSodium-dependent serotonin transporterHomo sapiens (human)
response to nutrientSodium-dependent serotonin transporterHomo sapiens (human)
memorySodium-dependent serotonin transporterHomo sapiens (human)
circadian rhythmSodium-dependent serotonin transporterHomo sapiens (human)
response to xenobiotic stimulusSodium-dependent serotonin transporterHomo sapiens (human)
response to toxic substanceSodium-dependent serotonin transporterHomo sapiens (human)
positive regulation of gene expressionSodium-dependent serotonin transporterHomo sapiens (human)
positive regulation of serotonin secretionSodium-dependent serotonin transporterHomo sapiens (human)
negative regulation of cerebellar granule cell precursor proliferationSodium-dependent serotonin transporterHomo sapiens (human)
negative regulation of synaptic transmission, dopaminergicSodium-dependent serotonin transporterHomo sapiens (human)
response to estradiolSodium-dependent serotonin transporterHomo sapiens (human)
social behaviorSodium-dependent serotonin transporterHomo sapiens (human)
vasoconstrictionSodium-dependent serotonin transporterHomo sapiens (human)
sperm ejaculationSodium-dependent serotonin transporterHomo sapiens (human)
negative regulation of neuron differentiationSodium-dependent serotonin transporterHomo sapiens (human)
positive regulation of cell cycleSodium-dependent serotonin transporterHomo sapiens (human)
negative regulation of organ growthSodium-dependent serotonin transporterHomo sapiens (human)
behavioral response to cocaineSodium-dependent serotonin transporterHomo sapiens (human)
enteric nervous system developmentSodium-dependent serotonin transporterHomo sapiens (human)
brain morphogenesisSodium-dependent serotonin transporterHomo sapiens (human)
serotonin uptakeSodium-dependent serotonin transporterHomo sapiens (human)
membrane depolarizationSodium-dependent serotonin transporterHomo sapiens (human)
platelet aggregationSodium-dependent serotonin transporterHomo sapiens (human)
cellular response to retinoic acidSodium-dependent serotonin transporterHomo sapiens (human)
cellular response to cGMPSodium-dependent serotonin transporterHomo sapiens (human)
regulation of thalamus sizeSodium-dependent serotonin transporterHomo sapiens (human)
conditioned place preferenceSodium-dependent serotonin transporterHomo sapiens (human)
sodium ion transmembrane transportSodium-dependent serotonin transporterHomo sapiens (human)
amino acid transportSodium-dependent serotonin transporterHomo sapiens (human)
monoamine transportSodium-dependent dopamine transporter Homo sapiens (human)
neurotransmitter transportSodium-dependent dopamine transporter Homo sapiens (human)
lactationSodium-dependent dopamine transporter Homo sapiens (human)
sensory perception of smellSodium-dependent dopamine transporter Homo sapiens (human)
locomotory behaviorSodium-dependent dopamine transporter Homo sapiens (human)
response to xenobiotic stimulusSodium-dependent dopamine transporter Homo sapiens (human)
response to iron ionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine transportSodium-dependent dopamine transporter Homo sapiens (human)
adenohypophysis developmentSodium-dependent dopamine transporter Homo sapiens (human)
response to nicotineSodium-dependent dopamine transporter Homo sapiens (human)
positive regulation of multicellular organism growthSodium-dependent dopamine transporter Homo sapiens (human)
regulation of dopamine metabolic processSodium-dependent dopamine transporter Homo sapiens (human)
response to cocaineSodium-dependent dopamine transporter Homo sapiens (human)
dopamine biosynthetic processSodium-dependent dopamine transporter Homo sapiens (human)
dopamine catabolic processSodium-dependent dopamine transporter Homo sapiens (human)
response to ethanolSodium-dependent dopamine transporter Homo sapiens (human)
cognitionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine uptake involved in synaptic transmissionSodium-dependent dopamine transporter Homo sapiens (human)
response to cAMPSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine uptakeSodium-dependent dopamine transporter Homo sapiens (human)
prepulse inhibitionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine uptakeSodium-dependent dopamine transporter Homo sapiens (human)
hyaloid vascular plexus regressionSodium-dependent dopamine transporter Homo sapiens (human)
amino acid transportSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine transportSodium-dependent dopamine transporter Homo sapiens (human)
sodium ion transmembrane transportSodium-dependent dopamine transporter Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (28)

Processvia Protein(s)Taxonomy
actin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
protein bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
alpha-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
metal ion bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
beta-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
integrin bindingSodium-dependent serotonin transporterHomo sapiens (human)
monoatomic cation channel activitySodium-dependent serotonin transporterHomo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent serotonin transporterHomo sapiens (human)
serotonin:sodium:chloride symporter activitySodium-dependent serotonin transporterHomo sapiens (human)
protein bindingSodium-dependent serotonin transporterHomo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent serotonin transporterHomo sapiens (human)
antiporter activitySodium-dependent serotonin transporterHomo sapiens (human)
syntaxin-1 bindingSodium-dependent serotonin transporterHomo sapiens (human)
cocaine bindingSodium-dependent serotonin transporterHomo sapiens (human)
sodium ion bindingSodium-dependent serotonin transporterHomo sapiens (human)
identical protein bindingSodium-dependent serotonin transporterHomo sapiens (human)
nitric-oxide synthase bindingSodium-dependent serotonin transporterHomo sapiens (human)
actin filament bindingSodium-dependent serotonin transporterHomo sapiens (human)
serotonin bindingSodium-dependent serotonin transporterHomo sapiens (human)
protease bindingSodium-dependent dopamine transporter Homo sapiens (human)
signaling receptor bindingSodium-dependent dopamine transporter Homo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent dopamine transporter Homo sapiens (human)
dopamine:sodium symporter activitySodium-dependent dopamine transporter Homo sapiens (human)
protein bindingSodium-dependent dopamine transporter Homo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent dopamine transporter Homo sapiens (human)
dopamine bindingSodium-dependent dopamine transporter Homo sapiens (human)
amine bindingSodium-dependent dopamine transporter Homo sapiens (human)
protein-containing complex bindingSodium-dependent dopamine transporter Homo sapiens (human)
metal ion bindingSodium-dependent dopamine transporter Homo sapiens (human)
protein phosphatase 2A bindingSodium-dependent dopamine transporter Homo sapiens (human)
heterocyclic compound bindingSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine:sodium symporter activitySodium-dependent dopamine transporter Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (19)

Processvia Protein(s)Taxonomy
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
cell surfaceSodium-dependent noradrenaline transporter Homo sapiens (human)
membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
neuronal cell body membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
presynaptic membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
axonSodium-dependent noradrenaline transporter Homo sapiens (human)
plasma membraneSodium-dependent serotonin transporterHomo sapiens (human)
focal adhesionSodium-dependent serotonin transporterHomo sapiens (human)
endosome membraneSodium-dependent serotonin transporterHomo sapiens (human)
endomembrane systemSodium-dependent serotonin transporterHomo sapiens (human)
presynaptic membraneSodium-dependent serotonin transporterHomo sapiens (human)
membrane raftSodium-dependent serotonin transporterHomo sapiens (human)
synapseSodium-dependent serotonin transporterHomo sapiens (human)
postsynaptic membraneSodium-dependent serotonin transporterHomo sapiens (human)
serotonergic synapseSodium-dependent serotonin transporterHomo sapiens (human)
synapseSodium-dependent serotonin transporterHomo sapiens (human)
plasma membraneSodium-dependent serotonin transporterHomo sapiens (human)
neuron projectionSodium-dependent serotonin transporterHomo sapiens (human)
cytoplasmSodium-dependent dopamine transporter Homo sapiens (human)
plasma membraneSodium-dependent dopamine transporter Homo sapiens (human)
cell surfaceSodium-dependent dopamine transporter Homo sapiens (human)
membraneSodium-dependent dopamine transporter Homo sapiens (human)
axonSodium-dependent dopamine transporter Homo sapiens (human)
neuron projectionSodium-dependent dopamine transporter Homo sapiens (human)
neuronal cell bodySodium-dependent dopamine transporter Homo sapiens (human)
axon terminusSodium-dependent dopamine transporter Homo sapiens (human)
membrane raftSodium-dependent dopamine transporter Homo sapiens (human)
postsynaptic membraneSodium-dependent dopamine transporter Homo sapiens (human)
dopaminergic synapseSodium-dependent dopamine transporter Homo sapiens (human)
flotillin complexSodium-dependent dopamine transporter Homo sapiens (human)
axonSodium-dependent dopamine transporter Homo sapiens (human)
presynaptic membraneSodium-dependent dopamine transporter Homo sapiens (human)
plasma membraneSodium-dependent dopamine transporter Homo sapiens (human)
neuronal cell body membraneSodium-dependent dopamine transporter Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (46)

Assay IDTitleYearJournalArticle
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID212885Compound dose that causes lethality (acute toxicity) was determined by administering perorally in mice.1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
3-[(2-ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity.
AID144700Noncompetitive inhibition of N-methyl-D-aspartate (NMDA) Receptor, by the displacement of [3H]MK-801 in rat brain membranes; nd means not determined1998Bioorganic & medicinal chemistry letters, Mar-03, Volume: 8, Issue:5
Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
AID159537Tested for in vitro reuptake inhibition of [3H]-5-hydroxy tryptamine in pig frontal synaptosomes.1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
3-[(2-ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity.
AID204080Equilibrium dissociation constant (KD) for Competitive binding between [3H]- imipramine and the compound at human transporter-hSERT1998Bioorganic & medicinal chemistry letters, Mar-03, Volume: 8, Issue:5
Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
AID130125Compound was evaluated for maximal electroshock antagonism (MES) against mice1984Journal of medicinal chemistry, May, Volume: 27, Issue:5
Synthesis and central nervous system properties of 2-[(alkoxycarbonyl)amino]-4(5)-phenyl-2-imidazolines.
AID1151051Antidepressant activity in po dosed mouse assessed as antagonism of reserpine-induced hypothermia dosed 17 hrs after reserpine challenge1976Journal of medicinal chemistry, Aug, Volume: 19, Issue:8
Optical isomers of 2-(2-ethoxyphenoxymethyl)tetrahydro-1,4-oxazine (viloxazine) and related compounds.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID132000Evaluated for antagonism of reserpine induced hypothermia; 0.5-2.5 mg/kg1984Journal of medicinal chemistry, May, Volume: 27, Issue:5
Synthesis and central nervous system properties of 2-[(alkoxycarbonyl)amino]-4(5)-phenyl-2-imidazolines.
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID159538Tested for in vitro reuptake inhibition of [3H]dopamine in pig striatal synaptosomes.1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
3-[(2-ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity.
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID186979Inhibition of [3H]- DA reuptake into rat striatal synaptosomes1998Bioorganic & medicinal chemistry letters, Mar-03, Volume: 8, Issue:5
Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID186980Inhibition of [3H]- NE reuptake into rat hippocampal synaptosomes1998Bioorganic & medicinal chemistry letters, Mar-03, Volume: 8, Issue:5
Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID109918Antidepressant activity was assessed from the ability to antagonize reserpine-induced palpebral ptosis on peroral administration in mice; value ranges from (0.7-3.3.)1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
3-[(2-ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity.
AID1151052Sedative activity in po dosed mouse assessed as reduction in locomotor activity during 60 mins period immediately prior to and after dosing1976Journal of medicinal chemistry, Aug, Volume: 19, Issue:8
Optical isomers of 2-(2-ethoxyphenoxymethyl)tetrahydro-1,4-oxazine (viloxazine) and related compounds.
AID109911Antidepressant activity was assessed from the ability to antagonize reserpine-induced hypothermia on peroral administration in mice; value ranges from(3.1-7.)1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
3-[(2-ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity.
AID127865Evaluated in vivo for reserpine hypothermia after oral administration in mouse. Minimum active dose was reported; 30-70% reduction1984Journal of medicinal chemistry, May, Volume: 27, Issue:5
Synthesis and central nervous system properties of 2-[(alkoxycarbonyl)amino]-4(5)-phenyl-2-imidazolines.
AID476929Human intestinal absorption in po dosed human2010European journal of medicinal chemistry, Mar, Volume: 45, Issue:3
Neural computational prediction of oral drug absorption based on CODES 2D descriptors.
AID64372Equilibrium dissociation constant (KD) for Competitive binding between [3H]WIN-35428 and the compound at human transporter-hDAT1998Bioorganic & medicinal chemistry letters, Mar-03, Volume: 8, Issue:5
Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
AID134948Mouse behavior activity was determined; S-D=Stimulant-Depressant1984Journal of medicinal chemistry, May, Volume: 27, Issue:5
Synthesis and central nervous system properties of 2-[(alkoxycarbonyl)amino]-4(5)-phenyl-2-imidazolines.
AID186981Inhibition of [3H]5-HT reuptake into rat frontal cortex synaptosomes1998Bioorganic & medicinal chemistry letters, Mar-03, Volume: 8, Issue:5
Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
AID110033Pentylenetetrazole antagonistic activity on peroral administration in mice; value ranges from(6.4-20.7).1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
3-[(2-ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID145563Equilibrium dissociation constant (KD) for Competitive binding between [3H]- nisoxatine and the compound at human Norepinephrine transporter1998Bioorganic & medicinal chemistry letters, Mar-03, Volume: 8, Issue:5
Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID134420Lethal dose in mouse, in groups of ten1984Journal of medicinal chemistry, May, Volume: 27, Issue:5
Synthesis and central nervous system properties of 2-[(alkoxycarbonyl)amino]-4(5)-phenyl-2-imidazolines.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID159539Tested for in vitro reuptake inhibition of [3H]norepinephrine in pig occipital synaptosomes.1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
3-[(2-ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity.
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID109909Amphetamine antagonistic activity on peroral administration in mice; value ranges from (13.2-22.4)1987Journal of medicinal chemistry, Jan, Volume: 30, Issue:1
3-[(2-ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (214)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990160 (74.77)18.7374
1990's23 (10.75)18.2507
2000's3 (1.40)29.6817
2010's3 (1.40)24.3611
2020's25 (11.68)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 67.90

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index67.90 (24.57)
Research Supply Index5.74 (2.92)
Research Growth Index5.52 (4.65)
Search Engine Demand Index115.02 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (67.90)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials65 (26.42%)5.53%
Reviews19 (7.72%)6.00%
Case Studies21 (8.54%)4.05%
Observational0 (0.00%)0.25%
Other141 (57.32%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (4)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase I/IIa Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Safety and Efficacy of SPN-812 in Adults With Attention Deficit Hyperactivity Disorder (ADHD) [NCT01107496]Phase 1/Phase 252 participants (Actual)Interventional2010-06-30Completed
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Flexible-Dose Study of the Efficacy and Safety of SPN-812 in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD) [NCT04016779]Phase 3374 participants (Actual)Interventional2019-11-20Completed
A Phase IV, Open-Label, Decentralized Clinical Trial to Evaluate the Efficacy and Safety of Qelbree® in Adults With Attention-Deficit/Hyperactivity Disorder and Mood Symptoms [NCT06185985]Phase 4750 participants (Anticipated)Interventional2024-01-31Not yet recruiting
Open-Label Extension Study to Evaluate the Long Term Safety and Efficacy of SPN-812 ER for the Treatment of Pediatric Patients With Attention-Deficit/Hyperactivity Disorder (ADHD) [NCT02736656]Phase 31,200 participants (Anticipated)Interventional2016-02-02Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT04016779 (22) [back to overview]"Effect of SPN-812 on the Emotional Control Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"
NCT04016779 (22) [back to overview]"Effect of SPN-812 on the Inhibit Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"
NCT04016779 (22) [back to overview]"Effect of SPN-812 on the Initiate Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"
NCT04016779 (22) [back to overview]"Effect of SPN-812 on the Organization of Materials Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"
NCT04016779 (22) [back to overview]"Effect of SPN-812 on the Plan/Organize Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"
NCT04016779 (22) [back to overview]"Effect of SPN-812 on the Self-Monitor Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"
NCT04016779 (22) [back to overview]"Effect of SPN-812 on the Shift Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"
NCT04016779 (22) [back to overview]"Effect of SPN-812 on the Task Monitor Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"
NCT04016779 (22) [back to overview]"Effect of SPN-812 on the Working Memory Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"
NCT04016779 (22) [back to overview]Effect of SPN-812 on 30% Clinical Response Rate as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS)
NCT04016779 (22) [back to overview]Effect of SPN-812 on 50% Clinical Response Rate as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS).
NCT04016779 (22) [back to overview]Effect of SPN-812 on Clinical Response Rate as Assessed by the Clinical Global Impression - Improvement (CGI-I) Scale
NCT04016779 (22) [back to overview]Effect of SPN-812 on Hyperactivity/Impulsivity Symptoms as Assessed by the Hyperactivity/Impulsivity Subscale of the Adult ADHD Investigator Symptom Rating Scale (AISRS)
NCT04016779 (22) [back to overview]Effect of SPN-812 on Inattention Symptoms as Assessed by the Inattention Subscale of the Adult ADHD Investigator Symptom Rating Scale (AISRS)
NCT04016779 (22) [back to overview]Effect of SPN-812 on Symptoms of Anxiety as Assessed by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale
NCT04016779 (22) [back to overview]Effect of SPN-812 on the Behavioral Regulation Index (BRI) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)
NCT04016779 (22) [back to overview]Effect of SPN-812 on the Clinical Global Impression - Improvement (CGI-I) Scale
NCT04016779 (22) [back to overview]Effect of SPN-812 on the Clinical Global Impression - Severity of Illness (CGI-S) Scale
NCT04016779 (22) [back to overview]Effect of SPN-812 on the Clinical Response Rate as Assessed by the Clinical Global Impression - Severity of Illness (CGI-S) Scale
NCT04016779 (22) [back to overview]Effect of SPN-812 on the Global Executive Composite (GEC) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)
NCT04016779 (22) [back to overview]Effect of SPN-812 on the Metacognitive Index (MI) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)
NCT04016779 (22) [back to overview]Efficacy of SPN-812 on Symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score

"Effect of SPN-812 on the Emotional Control Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"

"An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Emotional Control scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Emotional Control scale is one of four Behavioral Regulation Index-related scales; it captures an individual's ability to modulate their emotional responses appropriately. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 10 items yields the Emotional Control raw score (range: 10-30), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Emotional Control T-score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-4.0
SPN-812-3.1

[back to top]

"Effect of SPN-812 on the Inhibit Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"

"An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Inhibit scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Inhibit scale is one of four Behavioral Regulation Index-related scales; it captures the ability to control impulses, appropriately stop verbal, attentional, physical behavior at the proper time. Subject's rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 8 items yields the Inhibit raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Inhibit T-score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-6.4
SPN-812-7.8

[back to top]

"Effect of SPN-812 on the Initiate Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"

"An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Initiate scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Initiate scale is one of five Metacognition Index-related scales; it captures an individual's ability to begin a task or activity without external prompting and to independently generate ideas. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 8 items yields the Initiate scale raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Initiate T-score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-5.4
SPN-812-7.1

[back to top]

"Effect of SPN-812 on the Organization of Materials Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"

"An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Organization of Materials scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Organization of Materials scale is one of five Metacognition Index-related scales; it captures one's ability to keep areas orderly and maintain materials. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience within the last month. The sum of 8 items yields the Organization of Materials raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Organization of Materials T-score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-4.4
SPN-812-7.1

[back to top]

"Effect of SPN-812 on the Plan/Organize Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"

"An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Plan/Organize scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Plan/Organize scale is one of five Metacognition Index-related scales; it captures an individual's ability to anticipate events, set goals, pre-plan, organize, and carry out tasks systematically. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience within the last month. The sum of 10 items yields the Plan/Organize raw score (range: 10-30), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Plan/Organize T-score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-6.3
SPN-812-9.7

[back to top]

"Effect of SPN-812 on the Self-Monitor Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"

"An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Monitor scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Self-Monitor scale is one of four Behavioral Regulation Index-related scales; it reflects an individual's ability to recognize the effect of their own behavior on others. The subject rates each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 6 items yields the Self-Monitor raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Self-Monitor T-score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-6.7
SPN-812-7.3

[back to top]

"Effect of SPN-812 on the Shift Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"

"An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Shift scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Shift scale is one of four Behavioral Regulation Index-related scales; it captures one's ability to move freely from one situation/activity/aspect of problem to another and think flexibly to aid problem-solving. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 6 items yields the Shift raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Shift T-score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-4.8
SPN-812-7.2

[back to top]

"Effect of SPN-812 on the Task Monitor Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"

"An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Task Monitor scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Task Monitor scale is one of five Metacognition Index-related scales; it captures an individual's ability to assess performance for mistakes during or after finishing a task. The subject rates each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 6 items yields the Task Monitor raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Task Monitor T-score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-4.4
SPN-812-7.9

[back to top]

"Effect of SPN-812 on the Working Memory Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)"

"An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Working Memory scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Working Memory scale is one of five Metacognition Index-related scales; it captures one's ability to hold information in mind in order to complete a task and stay with, or stick to, an activity. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience within the last month. The sum of 8 items yields the Working Memory raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Working Memory T-score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-6.9
SPN-812-10.1

[back to top]

Effect of SPN-812 on 30% Clinical Response Rate as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS)

"An additional secondary endpoint was the percentage of subjects with a 30% or greater reduction in their change from baseline Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. A Total score is calculated by summating the ratings of all 18 items (range: 0-54; the higher the score, the more severe the symptoms). The Total score is converted to a percent change from baseline. 30% responder rate values can range between 0 and 100%. A higher percentage represents a greater number of subjects who are responders." (NCT04016779)
Timeframe: Baseline and Week 6

Interventionpercentage of subjects (Number)
Placebo47.6
SPN-81260.0

[back to top]

Effect of SPN-812 on 50% Clinical Response Rate as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS).

"An additional secondary endpoint was the percentage of subjects with a 50% or greater reduction in their change from baseline Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. A Total score is calculated by summating the ratings of all 18 items (range: 0-54; the higher the score, the more severe the symptoms). The Total score is converted to a percent change from baseline. 50% responder rate values can range between 0 and 100%. A higher percentage represents a greater number of subjects who are responders." (NCT04016779)
Timeframe: Baseline and Week 6

Interventionpercentage of subjects (Number)
Placebo32.9
SPN-81239.2

[back to top]

Effect of SPN-812 on Clinical Response Rate as Assessed by the Clinical Global Impression - Improvement (CGI-I) Scale

"An additional secondary endpoint was the percentage of subjects with a CGI-I score of 1 or 2 (responders) at Week 6. The CGI-I scale is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Responder rate values can range from 0 to 100%. A higher percentage represents a greater number of subjects who are responders." (NCT04016779)
Timeframe: Week 6

InterventionPercentage of subjects (Number)
Placebo37.8
SPN-81248.5

[back to top]

Effect of SPN-812 on Hyperactivity/Impulsivity Symptoms as Assessed by the Hyperactivity/Impulsivity Subscale of the Adult ADHD Investigator Symptom Rating Scale (AISRS)

"An additional secondary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Hyperactivity/Impulsivity subscale score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. The Hyperactivity/Impulsivity subscale score is calculated by summating the ratings of all 9 Hyperactivity/Impulsivity items (range: 0-27; the higher the score, the more severe the symptoms). A lower change from baseline Hyperactivity/Impulsivity subscale score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

Interventionunits on a scale (Least Squares Mean)
Placebo-5.8
SPN-812-7.2

[back to top]

Effect of SPN-812 on Inattention Symptoms as Assessed by the Inattention Subscale of the Adult ADHD Investigator Symptom Rating Scale (AISRS)

"An additional secondary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Inattention subscale score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. The Inattention subscale score is calculated by summating the ratings of all 9 Inattention items (range: 0-27; the higher the score, the more severe the symptoms). A lower change from baseline Inattention subscale score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

Interventionunits on a scale (Least Squares Mean)
Placebo-6.1
SPN-812-8.5

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Effect of SPN-812 on Symptoms of Anxiety as Assessed by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale

"An additional secondary endpoint was the change from baseline in the Generalized Anxiety Disorder 7-Item (GAD-7) Total score at Week 6. The GAD-7 is a self-reported 7-item questionnaire for screening and measuring the severity of generalized anxiety disorder. The subject rates each item on 4-point scale (0-3), where 0 = Not at all, 1 = Several days, 2 = Over half the days, and 3 = Nearly every day. The total score is calculated by summated the ratings of all 7 items. The total score can range between 0 to 21; the higher the score, the more severe the symptoms of anxiety. A lower change from baseline GAD-7 total score (<0) represents a better outcome." (NCT04016779)
Timeframe: Baseline and Week 6

Interventionunits on a scale (Least Squares Mean)
Placebo-1.6
SPN-812-1.6

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Effect of SPN-812 on the Behavioral Regulation Index (BRI) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Behavioral Regulation Index (BRI) T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The BRI captures the ability to maintain appropriate regulatory control of one's own behavior and emotional responses. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 30 items yields the BRI raw score (range: 30-90), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline BRI T-score (<0) represents a better outcome. (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-6.4
SPN-812-7.2

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Effect of SPN-812 on the Clinical Global Impression - Improvement (CGI-I) Scale

"An additional secondary endpoint was the Clinical Global Impression - Improvement (CGI-I) score at Week 6. The CGI-I scale is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. A CGI-I score <4 represents a better outcome." (NCT04016779)
Timeframe: Week 6

Interventionunits on a scale (Least Squares Mean)
Placebo2.9
SPN-8122.6

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Effect of SPN-812 on the Clinical Global Impression - Severity of Illness (CGI-S) Scale

The Key Secondary Endpoint was the change from baseline in the Clinical Global Impression - Severity of Illness (CGI-S) score at Week 6. The CGI-S is a single item clinician-rated assessment of the severity of subject's condition (ADHD symptoms) in relation to the clinician's total experience with patients with ADHD. The CGI-S is evaluated on a 7-point scale with 1 = Normal, not at all ill, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients. Successful therapy is indicated by a lower overall score in subsequent testing. A lower change from baseline CGI-S score (<0) represents a better outcome. (NCT04016779)
Timeframe: Baseline and Week 6

Interventionunits on a scale (Least Squares Mean)
Placebo-1.0
SPN-812-1.4

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Effect of SPN-812 on the Clinical Response Rate as Assessed by the Clinical Global Impression - Severity of Illness (CGI-S) Scale

"An additional secondary endpoint was the percentage of subjects with a Clinical Global Impression - Severity of Illness (CGI-S) score of 1 or 2 (responders) at Week 6. The CGI-S is a single item clinician-rated assessment of the severity of subject's condition (ADHD symptoms) in relation to the clinician's total experience with patients with ADHD. The CGI-S is evaluated on a 7-point scale with 1 = Normal, not at all ill, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients. Responder rate values range from 0 to 100%. A higher percentage represents a greater number of subjects who are responders." (NCT04016779)
Timeframe: Week 6

Interventionpercentage of subjects (Number)
Placebo25.2
SPN-81230.8

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Effect of SPN-812 on the Global Executive Composite (GEC) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Global Executive Composite (GEC) T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning (GEC) and 9 non-overlapping scales among 2 summary index scales (Metacognition Index [MI] and Behavioral Regulation Index [BRI]) that assess aspects of executive function and problems with self-regulation from the perspective of the individual. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 70 items yields the GEC raw score (range: 70-210), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline GEC T-score (<0) represents a better outcome. (NCT04016779)
Timeframe: Baseline and Week 6

InterventionT-score (Least Squares Mean)
Placebo-6.8
SPN-812-9.3

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Effect of SPN-812 on the Metacognitive Index (MI) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Metacognition Index (MI) T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. MI reflects individual's ability to problem solve (includes initiate activity, generate ideas, sustain working memory, plan/organize approaches, monitor success/failure, and organize materials/environment). Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 40 items yields the MI raw score (range: 40-120), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline MI T-score (<0) represents a better outcome. (NCT04016779)
Timeframe: Baseline and week 6

InterventionT-score (Least Squares Mean)
Placebo-6.5
SPN-812-9.8

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Efficacy of SPN-812 on Symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score

The Primary Endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. A Total score is calculated by summating the ratings of all 18 items (range: 0-54; the higher the score, the more severe the ADHD symptoms). A lower change from baseline AISRS Total score (<0) represents a better outcome. (NCT04016779)
Timeframe: Baseline and Week 6

Interventionunits on a scale (Least Squares Mean)
Placebo-11.7
SPN-812-15.5

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