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NV-5138

Phase 2

Major Depressive Disorder | Small molecule | Psychiatry |Supernus Pharmaceuticals, Inc.|Last Updated: Apr 17, 2026

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLEDBiomarker
Total Trials1
Total Enrollment40

FDA Designations

No designations recorded

Clinical trial landscape

NV-5138 · 4 trials · 3 indications

Phase 2 2Phase 1 2
NCT06235905Open-Label of SPN-820 in Adults With Major Depressive DisorderMajor Depressive Disorder
COMPLETED40 Analytics
NCT05066672Phase 2 Study of NV-5138 in Adults With Treatment Resistant DepressionTreatment Resistant Depression
COMPLETED250 Analytics
PHASE2COMPLETED
Open-Label of SPN-820 in Adults With Major Depressive Disorder
Major Depressive DisorderUnlock trial analytics
PHASE2COMPLETED
Phase 2 Study of NV-5138 in Adults With Treatment Resistant Depression
Treatment Resistant DepressionUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline to Each Time Point in the Hamilton Depression Rating Scale-6 Items (HAM-D6) Total Score (HAM-D6).
10 days (end of study)

The HAM-D6 scale consists of 6 items: five of them (depressed mood, work and activities, feeling of guilt, anxiety, psychic, retardation) are scored on a scale of 0 to 4, and one item (somatic symptoms general) is scored on a scale 0 to 2. The total score is the sum of the 6 items ranging from 0 to 22, higher scores indicate severe depression, and lower scores are better outcomes.

Change From Baseline to Week 4 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score.
Baseline to Week 4

MADRS is a 10-item scale (Reported sadness, Apparent sadness, Inner tension, Reduced sleep, Reduced appetite, Concentration difficulties, Lassitude, Inability to feel, Pessimist thoughts, and Suicidal thoughts) where each item is scored from 0 to 6. The total score is the sum of the 10 items ranging from 0 to 60 where higher scores indicate more severe depression, and lower scores are better outcomes. A negative change from baseline indicates improvement in depressive symptoms.

Cumulative total radioactivity in urine and faeces
urine and fecal samples up to 168 hours post dose

The percentage of the radioactive dose recovered in urine, faeces and in total

Secondary Endpoints

Change From Baseline to Each Time Point in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score.
10 days (end of study)
Change From Baseline to Each Time Point in the Clinical Global Impression - Severity of Illness Score (CGI-S).
10 days (end of study)
Suicidal Ideation and Behavior as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
10 days (end of study)
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
SPN-820 6 x 400 mg capsulesOTHER -
NV-5138 400 mg oral capsulesEXPERIMENTALParticipants received either 800 or 1600 mg NV-5138 (2 or 4, 400 mg capsules) once daily for 4 weeks. During the first week of the Treatment Period, all participants took 1600 mg once a day. Participants who experienced an intolerable adverse effect at 1600 mg at Week 2, could have their dose reduced to 800 mg. Participants who had an inadequate response to 800 mg might have their dose increased again to 1600 mg per Investigator judgment to maximize their treatment response; however, no dose adjustments were allowed after Week 3. The dose at Week 4 was the same as stable dose at Week 3. After completion of the 4-week treatment, all participants received placebo in a double-blinded fashion and continued the treatment for one week.
matched placeboPLACEBO_COMPARATORParticipants received either 2 or 4 capsules of placebo once daily for 5 weeks.
[14C]-NV-5138EXPERIMENTAL\[14C\]-NV-5138 oral solution

Interventions

NameTypeDescription
NV-5138DRUGNV-5138 is a novel, orally bioavailable, mechanistic target of rapamycin complex 1 (mTORC1) signaling enhancer
matched placeboDRUGmatched placebo oral capsules
[14C]-NV-5138DRUGSingle dose, given as oral solution, 1600 mg
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Eligibility Criteria

Age Range18 Years to 65 Years
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: * Male or female subject, aged 18 to 65 years (inclusive) at screening. * Diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) for either recurrent or single episode MDD without psychotic features that is confirmed by the M...

Countries:United StatesUnited Kingdom
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Frequently asked questions about NV-5138

What is NV-5138 used for?

NV-5138 is an investigational small molecule being studied for major depressive disorder and treatment resistant depression. It has also been evaluated in healthy volunteers in early phase studies. The drug is not approved and remains in clinical development.

Who makes NV-5138?

NV-5138 is being developed by Supernus Pharmaceuticals, Inc., a company traded on the NASDAQ under the ticker symbol SUPN. The company has sponsored clinical trials of the drug in the United States and the United Kingdom.

What phase is NV-5138 in?

NV-5138 is in Phase 1 and Phase 2 clinical development. It has completed Phase 1 mass balance studies in healthy volunteers and a Phase 2 study in adults with treatment resistant depression. The drug is investigational and not FDA approved.

What clinical trials is NV-5138 in?

NV-5138 has been studied in several completed trials. NCT05066672 was a Phase 2 study in 250 adults with treatment resistant depression in the United States. NCT05152680 and NCT05384977 were Phase 1 mass balance studies in healthy male subjects in the United Kingdom. NCT06235905 was an open-label Phase 2 study in 40 adults with major depressive disorder.

Is NV-5138 the same as SPN-820?

NV-5138 is also known as SPN-820. Clinical trial NCT06235905, an open-label study in adults with major depressive disorder, refers to the drug as SPN-820. Both names refer to the same investigational compound developed by Supernus Pharmaceuticals.

What does NV-5138 target?

NV-5138 is a small molecule being studied for its effects on major depressive disorder and treatment resistant depression. The specific molecular target of the drug has not been disclosed in the available clinical trial information.