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Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Evidence synthesis · §4

Semax in cognitive performance and neuroprotection: tolerability and discontinuation — summary of findings

Outcome-by-outcome summary with effect, certainty and the reason for each downgrade.

Document identifier
CEI-ES-114/4
Series
Evidence synthesis
Version
3.0
Published
11 Jul 2024
Last reviewed
11 Jan 2025
Next review
11 Jul 2026
Identifier
10.71829/cei.syn.114
Certainty
Very low
Cycle
2024 Q3
Review type
Safety review
Search executed
25 Mar 2024

Templated review frame. This review question was generated by crossing an indication with a compound for which contributing trials exist. Its prose frame is templated and is shared with other questions of the same shape. Its included studies, its summary of findings and its certainty rating are computed from the underlying records and are not templated. The Institute publishes these questions because the alternative is to leave a question the document set can answer unanswered, and it labels them because the alternative is to present a templated frame as an authored one.

§4Summary of findings

§4.1Summary of findings

Table 7. Summary of findings for Semax in cognitive performance and neuroprotection: tolerability and discontinuation.

OutcomeParticipants (studies)Effect as reportedCertaintyReason for downgrade
Domain-specific cognitive test scoresThe outcome the Institute designates as anchor for this indication.— (2)Registered in the Russian Federation on a national evidence base the Institute has not been able to retrieve in full. No trial…Very lowrisk of bias, inconsistency, publication bias
Discontinuation for adverse eventsReported as a summary-of-findings row rather than in a tolerability annex, following a public submission.— (1)Reported per contributing trial; see the included-studies tableVery lowinconsistency, indirectness, imprecision
Serious adverse eventsEvent counts are low; the estimate is imprecise by construction.— (1)Reported per contributing trial; see the included-studies tableVery lowindirectness, publication bias
Any adverse eventAscertained by spontaneous report in the contributing trials.— (1)Reported per contributing trial; see the included-studies tableVery lowinconsistency, indirectness
Clinical Dementia Rating sum of boxesA secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it.— (1)Reported as a secondary outcome in a subset of contributing trialsVery lowinconsistency, indirectness, imprecision
Biomarker change (amyloid, tau, neurofilament light)A secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it.— (1)Reported as a secondary outcome in a subset of contributing trialsVery lowinconsistency, imprecision
Certainty ratings describe confidence in the effect estimate for the stated outcome. They are not recommendations and do not transfer between outcomes.

§4.2Forest plot

Contributing estimatesPoint estimates with confidence intervals for each contributing study, plotted against the line of no effect.11.5Ratio measure, log scale (1 = no effect)Contributing studyEstimate (95 % CI)SEMAX-RU-COGNITIVE · n=not held1.18 (0.97 to 1.38)SEMAX-RU-STROKE · n=not held1.22 (0.96 to 1.47)Pooled estimate1.20 (1.06 to 1.36)
Study estimatePooled estimate
Figure 1. Illustrative. Contributing estimates plotted against the line of no effect. The point estimates and intervals are the Institute's standardised representation of the contributing evidence on a common ratio scale, generated deterministically from the record identifiers; they are not the published estimates, which appear in their own units in the included-studies table and on each trial abstract. The figure is published to convey the dispersion of the evidence base, not to supply a number.

§4.3Certainty assessment for the anchor outcome

Certainty assessment by domainDowngrading decision recorded for each certainty domain.Certainty domainNo concernSeriousVery seriousEffect on ratingRisk of biasdowngrade one levelInconsistencydowngrade one levelIndirectnessno downgradeImprecisionno downgradePublication biasdowngrade one levelTotal downgrading: 3 levelsVery low certainty
Figure 2. Domain-by-domain certainty assessment for the anchor outcome of this review.

Table 8. Reasoning recorded against each certainty domain for the anchor outcome.

DomainRatingReasoning
Risk of biasSeriousContributing trials are sponsor-conducted and one is open-label.
InconsistencySeriousEstimates vary in magnitude across contributing trials beyond what chance would produce.
IndirectnessNo concernNo serious concern identified in this domain.
ImprecisionNo concernNo serious concern identified in this domain.
Publication biasSeriousThe evidence base is small, recent and wholly sponsor-generated.
Overall: Very low certainty. The Institute has very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate. In this series a very low rating most often reflects an absence of controlled human evidence rather than conflicting evidence.

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
  2. Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256

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