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NCT03748706

PTI-125 for Mild-to-moderate Alzheimer's Disease Patients

Completed Phase 2 Results posted Last updated 7 July 2021
What this trial tests

Phase 2 trial testing PTI-125, 100 mg tablets in Alzheimer Disease in 13 participants. Completed in 8 May 2019.

Timeline
7 March 2019
Primary endpoint
8 May 2019
8 May 2019

Quick facts

Lead sponsorPain Therapeutics
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment13
Start date7 March 2019
Primary completion8 May 2019
Estimated completion8 May 2019
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Pain Therapeutics — full company profile →

Who can join

Adults 50 to 85, any sex, with Alzheimer Disease. 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.

Maximum Plasma Concentration (Cmax) Primary · Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

Blood draws will be done to evaluate levels of PTI-125 in the plasma using non-compartmental methods in WinNonlin.

Day 1 Cmax
GroupValue95% CI
PTI-1251020± 442
Day 28 Cmax
GroupValue95% CI
PTI-1251100± 417
Time to Maximum Plasma Concentration (Tmax) Primary · Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

Levels of PTI-125 will be assessed to determine how long it takes to reach the Cmax

Day 1 Tmax
GroupValue95% CI
PTI-1252.001.00 – 3.00
Day 28 Tmax
GroupValue95% CI
PTI-1252.061.00 – 5.93
Last Quantifiable Plasma Concentration (Clast) Primary · Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

Levels of PTI-125 will be assessed to determine the last time point where PTI-125 can be detected.

Day 1 Clast
GroupValue95% CI
PTI-125176± 112
Day 28 Clast
GroupValue95% CI
PTI-125238± 168
Time to Last Quantifiable Plasma Concentration (Tlast) Primary · Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

Levels of PTI-125 will be assessed to determine the elapsed time to where PTI-125 can last be detected in the plasma.

Day 1 Tlast
GroupValue95% CI
PTI-12512.0± 0.0150
Day 28 Tlast
GroupValue95% CI
PTI-12512.0± 0.0285
Area Under the Curve (AUClast) Primary · Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

AUC for PTI-125 plasma concentration from time zero to the last quantifiable plasma concentration.

Day 1 AUClast
GroupValue95% CI
PTI-1255320± 2230
Day 28 AUClast
GroupValue95% CI
PTI-1256700± 3240
Plasma Half-life (T1/2) Primary · Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

Assessment of the half-life in plasma of PTI-125

Day 1 T1/2
GroupValue95% CI
PTI-1254.51± 2.43
Day 28 T1/2
GroupValue95% CI
PTI-1254.35± 1.39
SavaDx (Biomarker) Secondary · Study Day 1 and Day 28

Blood samples will be tested for the complementary diagnostic/biomarker for Alzheimer's disease.

GroupValue95% CI
PTI-125-39.8± 0.19
CSF Biomarkers Secondary · Change from Baseline to Day 28

A cerebrospinal fluid sample collection will be performed for Aβ42, tau, YKL40 and other potential CSF biomarkers

Total tau
GroupValue95% CI
PTI-125-19.8± 0.04
Abeta42
GroupValue95% CI
PTI-1254.3± 0.05
p-tau181
GroupValue95% CI
PTI-125-34.4± 0.05
Neurogranin
GroupValue95% CI
PTI-125-32± 0.02
Neurofilament light chain
GroupValue95% CI
PTI-125-22± 0.02
YKL-40
GroupValue95% CI
PTI-125-9± 0.01
IL-6
GroupValue95% CI
PTI-125-14± 0.01
IL-1 beta
GroupValue95% CI
PTI-125-11± 0.01

Adverse events — posted to ClinicalTrials.gov

Time frame: Within the 28-day treatment period.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PTI-125
Serious: 0/13 (0%)
Deaths: 0/13
Other adverse events (6 terms — click to expand)

ReactionSystemPTI-125
FallGeneral disorders
B12 deficiencyMetabolism and nutrition disorders
HypercalcemiaMusculoskeletal and connective tissue disorders
Renal colicRenal and urinary disorders
DehydrationGeneral disorders
FluRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT03748706 adverse events section.

Sponsor's own description

This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate Alzheimer's disease patients.

Publications & conference data

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

  1. Alzheimer's disease drug development pipeline: 2019.
    Cummings J, Lee G, Ritter A, Sabbagh M, et al · · 2019 · cited 485× · PMID 31334330 · DOI 10.1016/j.trci.2019.05.008
  2. Filamin A inhibition reduces seizure activity in a mouse model of focal cortical malformations.
    Zhang L, Huang T, Teaw S, Nguyen LH, et al · · 2020 · cited 42× · PMID 32075941 · DOI 10.1126/scitranslmed.aay0289
  3. Promising candidates from drug clinical trials: Implications for clinical treatment of Alzheimer's disease in China.
    Cao Y, Yu F, Lyu Y, Lu X. · · 2022 · cited 16× · PMID 36457865 · DOI 10.3389/fneur.2022.1034243
  4. A Systematic Review on Drugs Acting as Nicotinic Acetylcholine Receptor Agonists in the Treatment of Dementia.
    Crestini A, Carbone E, Rivabene R, Ancidoni A, et al · · 2024 · cited 11× · PMID 38334629 · DOI 10.3390/cells13030237
  5. Simufilam suppresses overactive mTOR and restores its sensitivity to insulin in Alzheimer's disease patient lymphocytes.
    Wang HY, Pei Z, Lee KC, Nikolov B, et al · · 2023 · cited 7× · PMID 37457922 · DOI 10.3389/fragi.2023.1175601
  6. The potential of ARL4C and its-mediated genes in atherosclerosis and agent development.
    Liu D, Wang J, Zhang S, Jiang H, et al · · 2025 · PMID 40176913 · DOI 10.3389/fphar.2025.1513340

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