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NCT05318937

A Study to Evaluate the Effects of SAGE-718 in Participants With Parkinson's Disease Cognitive Impairment

Completed Phase 2 Results posted Last updated 12 September 2025
What this trial tests

Phase 2 trial testing SAGE-718-matching placebo in Parkinson Disease in 86 participants. Completed in 23 February 2024.

Timeline
6 June 2022
Primary endpoint
17 January 2024
23 February 2024

Quick facts

Lead sponsorSupernus Pharmaceuticals, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment86
Start date6 June 2022
Primary completion17 January 2024
Estimated completion23 February 2024
Sites38 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Supernus Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 50 to 75, any sex, with Parkinson Disease or Cognitive Dysfunction. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score Primary · Baseline, Day 42

The WAIS-IV coding test is a valid and sensitive measure of cognitive dysfunction that correlates with real-world functional outcomes (e.g., the ability to accomplish everyday tasks) and recovery from functional disability used to assess processing speed. The participant is required to identify the symbols matched to numbers using a key and write in the symbol beneath the associated number. The total score ranges from 0 to 135 and is based on the total number of codes correctly completed over a 120-second time limit. Higher scores indicate better processing speed. Positive change from baseline

GroupValue95% CI
Placebo2.0± 1.44
SAGE-7182.0± 1.48
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) Secondary · Up to Day 70

An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing

GroupValue95% CI
Placebo27
SAGE-71821
Number of Participants With at Least One TEAE by Severity Secondary · Up to Day 70

A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Severity was assessed as: * Mild: symptoms barely noticeable to participant or does not make participant uncomfortable; does not influence performance or functioning; prescription drug not ordinarily needed for relief of symptoms * Moderate: symptoms of a sufficient severity to make participant uncomfortable; performance of daily activity is influenced; participant is able to continue in study; treatment for symptoms ma

Mild
GroupValue95% CI
Placebo15
SAGE-71814
Moderate
GroupValue95% CI
Placebo10
SAGE-7185
Severe
GroupValue95% CI
Placebo2
SAGE-7182
Number of Participants Who Withdrew From Study Due to TEAEs Secondary · Up to Day 70

An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing medical conditi

GroupValue95% CI
Placebo0
SAGE-7180

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 70. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 2/43 (5%)
Deaths: 1/43
SAGE-718
Serious: 3/43 (7%)
Deaths: 0/43

Serious adverse events (8 terms)

ReactionSystemPlaceboSAGE-718
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myocardial infarctionCardiac disorders
UrosepsisInfections and infestations
FallInjury, poisoning and procedural complications
Rib fractureInjury, poisoning and procedural complications
ArthralgiaMusculoskeletal and connective tissue disorders
Toxic encephalopathyNervous system disorders
Other adverse events (2 terms — click to expand)

ReactionSystemPlaceboSAGE-718
Urinary tract infectionRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Breast cancer, Lung neoplasm malignant, Acute myocardial infarction, Urosepsis, Fall, Rib fracture, Arthralgia, Toxic encephalopathy.

Data from ClinicalTrials.gov NCT05318937 adverse events section.

Sponsor's own description

The primary purpose of this study is to evaluate the effect of SAGE-718 on cognitive performance in participants with Parkinson's disease mild cognitive impairment (PD-MCI).

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.
    Hanson JE, Yuan H, Perszyk RE, Banke TG, et al · · 2024 · cited 79× · PMID 37369776 · DOI 10.1038/s41386-023-01614-3
  2. Cognitive Impairment in Parkinson's Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches.
    Degirmenci Y, Angelopoulou E, Georgakopoulou VE, Bougea A. · · 2023 · cited 32× · PMID 37893474 · DOI 10.3390/medicina59101756
  3. GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology.
    Ge Y, Wang YT. · · 2023 · cited 29× · PMID 37324591 · DOI 10.3389/fnmol.2023.1190324
  4. Parkinson's disease therapy: what lies ahead?
    Wolff A, Schumacher NU, Pürner D, Machetanz G, et al · · 2023 · cited 19× · PMID 37147404 · DOI 10.1007/s00702-023-02641-6
  5. Dysfunction of the NMDA Receptor in the Pathophysiology of Schizophrenia and/or the Pathomechanisms of Treatment-Resistant Schizophrenia.
    Okubo R, Okada M, Motomura E. · · 2024 · cited 12× · PMID 39334894 · DOI 10.3390/biom14091128
  6. Mechanisms of Transsynaptic Degeneration in the Aging Brain.
    Wall RV, Basavarajappa D, Klistoner A, Graham S, et al · · 2024 · cited 7× · PMID 39191395 · DOI 10.14336/ad.2024.03019

Verify or expand the search:

Other trials of SAGE-718

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing