Alzheimer DiseasePhase 2NCT03748706
PTI-125 for Mild-to-moderate Alzheimer's Disease Patients
A Phase 2 study testing PTI-125, 100 mg tablets in people with Alzheimer Disease, run by Pain Therapeutics at 2 sites in United States.
Trial summary
This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate Alzheimer's disease patients. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- PTI-125, 100 mg tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Mar 2019to 8 May 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages >= 50 and <= 85 years
- Informed consent form (ICF) signed by the subject or legally acceptable representative.
- Clinical diagnosis of dementia due to possible or probable Alzheimer's disease
- Mini-Mental State Examination score >= 16 and <= 24 at screening
- If female, postmenopausal for at least 1 year
- Patient living at home, senior residential setting, or an institutional setting without the need for continuous (i.e. 24-hour) nursing care
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- General health status acceptable for participation in the study
- Fluency (oral and written) in English or Spanish
- If receiving memantine, rivastigmine, galantamine or an AChEI, receiving a stable dose for at least 3 months (90 days) before screening and with continuous dosing for at least 3 months. If receiving donepezil, receiving any dose lower than 23 mg once daily.
- The patient is a non-smoker for at least 12 months.
- The patient or legal representative must agree to comply with the drawing of blood samples and with a lumbar puncture and the drawing of cerebrospinal fluid samples.
- The patient has a ratio of total tau/Abeta42 in cerebrospinal fluid >= 0.30.
- Patient has a caregiver or legal representative responsible for administering the drug and recording the time.
Who cannot join
- Exposure to an experimental drug, experimental biologic or experimental medical device within the longer of 5 half-lives or 3 months before screening
- Residence in a skilled nursing facility
- Clinically significant laboratory test results
- Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating hormone level and thyroid supplementation dose must be stable for at least 6 months before screening)
- Insufficiently controlled diabetes mellitus or requiring insulin
- Renal insufficiency (serum creatinine >2.0 mg/dL)
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- Malignant tumor within 3 years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or localized prostate cancer or localized stage 1 bladder cancer)
- History of ischemic colitis or ischemic enterocolitis
- Unstable medical condition that is clinically significant in the judgment of the investigator
- Alanine transaminase (ALT) or aspartate transaminase (AST) >2 times the upper limit of normal or total bilirubin greater than the upper limit of normal.
- History of myocardial infarction or unstable angina within 6 months before screening
- History of more than 1 myocardial infarction within 5 years before screening
- Clinically significant cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (patients with a pacemaker are acceptable)
- Symptomatic hypotension, or uncontrolled hypertension
- Clinically significant abnormality on screening electrocardiogram (ECG), including but not necessarily limited to a confirmed corrected QT value >= 450 msec for males or >= 470 msec for females.
- Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia
- History of brain tumor or other clinically significant space-occupying lesion on CT or MRI
- Head trauma with clinically significant loss of consciousness within 12 months before screening or concurrent with the onset of dementia
- Onset of dementia secondary to cardiac arrest, surgery with general anesthesia, or resuscitation
- Specific degenerative CNS disease diagnosis other than Alzheimer's disease (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)
- Wernicke's encephalopathy
- Active acute or chronic Central Nervous System infection
- Donepezil 23 mg or greater quaque die currently or within 3 months prior to enrollment in the study
- Discontinued AChEI < 30 days prior to enrollment in the study
- Antipsychotics; low doses are allowed only if given for sleep disturbances, agitation and/or aggression, and only if the subject has received a stable dose for at least 3 months before enrollment in the study
- Tricyclic antidepressants and monoamine oxidase inhibitors; all other antidepressants are allowed only if the subject has received a stable dose for at least 3 months before enrollment in the study
- Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem are allowed only if given for insomnia/sleep disturbance, and only if the subject has received a stable dose for at least 3 months before enrollment in the study
- Peripherally acting drugs with effects on cholinergic transmission
- Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses (Steroid use for allergy or other inflammation is permitted.)
- Antiepileptic medications if taken for control of seizures
- Chronic intake of opioid-containing analgesics
- Sedating H1 antihistamines
- Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening
- Clinically significant illness within 30 days of enrollment
- History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease
- Positive serum hepatitis B surface antigen (HBsAg) or positive hepatitis C virus (HCV) antibody test at screening
- Positive HIV test at screening
- Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study
- Metformin or cimetidine.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Insite Clinical Research
DeSoto, Texas, 75115
Clinical Trials of Texas
San Antonio, Texas, 78229
About this study
Official title: A Phase 2a, Open-label, Multiple Dose, Safety, Pharmacokinetic and Biomarker Study of PTl-125 in Mild-to-moderate Alzheimer's Disease Patients
This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate Alzheimer's disease patients.
Read the detailed description
This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate AD patients, 50-85 years of age. A total of twelve (12) patients will be enrolled into the study. Patients will receive 100 mg b.i.d. of PTI-125. The objectives of this study are to investigate the safety, pharmacokinetics and effect on biomarkers of PTI-125 following 28-day repeat-dose oral administration.
- Conditions
- Alzheimer Disease
- Being tested
- PTI-125, 100 mg tablets
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTI-125, 100 mg tabletsDrug
PTI-125, 100 mg tablets taken twice a day for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Simufilam (PTI-125) | Experimental | Simufilam (PTI-125) 100 mg oral tablets administered twice daily (BID) Receives: Drug: PTI-125, 100 mg tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax)
Blood draws will be done to evaluate levels of PTI-125 in the plasma using non-compartmental methods in WinNonlin.
Measured: 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
Time to Maximum Plasma Concentration (Tmax)
Levels of PTI-125 will be assessed to determine how long it takes to reach the Cmax
Measured: 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
Last Quantifiable Plasma Concentration (Clast)
Levels of PTI-125 will be assessed to determine the last time point where PTI-125 can be detected.
Measured: 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
Time to Last Quantifiable Plasma Concentration (Tlast)
Levels of PTI-125 will be assessed to determine the elapsed time to where PTI-125 can last be detected in the plasma.
Measured: 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
Area Under the Curve (AUClast)
AUC for PTI-125 plasma concentration from time zero to the last quantifiable plasma concentration.
Measured: 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
Plasma Half-life (T1/2)
Assessment of the half-life in plasma of PTI-125
Measured: 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
Secondary outcomes (2)
SavaDx (Biomarker)
Blood samples will be tested for the complementary diagnostic/biomarker for Alzheimer's disease.
Measured: Study Day 1 and Day 28
CSF Biomarkers
A cerebrospinal fluid sample collection will be performed for Aβ42, tau, YKL40 and other potential CSF biomarkers
Measured: Change from Baseline to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2018
- Study start7 Mar 2019
- Primary completion8 May 2019
- Study completion8 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pain Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Lindsay Burns, PhD, Study director, Cassava Sciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03748706
- Sponsor's protocol ID
- PTI-125-03
- Other IDs
- R44AG060878
- Status last verified
- Jun 2021
- First submitted
- 13 Nov 2018
- Last updated
- 7 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang HY, Lee KC, Pei Z, Khan A, Bakshi K, Burns LH. PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis. Neurobiol Aging. 2017 Jul;55:99-114. doi: 10.1016/j.neurobiolaging.2017.03.016. Epub 2017 Mar 31.
PubMed 28438486Wang HY, Bakshi K, Frankfurt M, Stucky A, Goberdhan M, Shah SM, Burns LH. Reducing amyloid-related Alzheimer's disease pathogenesis by a small molecule targeting filamin A. J Neurosci. 2012 Jul 18;32(29):9773-84. doi: 10.1523/JNEUROSCI.0354-12.2012.
PubMed 22815492Wang HY, Pei Z, Lee KC, Lopez-Brignoni E, Nikolov B, Crowley CA, Marsman MR, Barbier R, Friedmann N, Burns LH. PTI-125 Reduces Biomarkers of Alzheimer's Disease in Patients. J Prev Alzheimers Dis. 2020;7(4):256-264. doi: 10.14283/jpad.2020.6.
PubMed 32920628
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Open-label, Multiple Dose, Safety, Pharmacokinetic and Biomarker Study of PTl-125 in Mild-to-moderate Alzheimer's Disease Patients
- ClinicalTrials.gov ID
- NCT03748706
- Acronym / sponsor ID
- PTI-125-03
- Conditions
- Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Pain TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 7 Mar 2019 (actual)
- Primary completion
- 8 May 2019 (actual)
- Study completion
- 8 May 2019 (actual)
- First posted
- 21 Nov 2018 (actual)
- Results
- Posted 1 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate Alzheimer's disease patients.
Detailed description
This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate AD patients, 50-85 years of age. A total of twelve (12) patients will be enrolled into the study. Patients will receive 100 mg b.i.d. of PTI-125. The objectives of this study are to investigate the safety, pharmacokinetics and effect on biomarkers of PTI-125 following 28-day repeat-dose oral administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Simufilam (PTI-125) | Experimental | Drug: PTI-125, 100 mg tabletsSimufilam (PTI-125) 100 mg oral tablets administered twice daily (BID) |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Ages >= 50 and <= 85 years
- Informed consent form (ICF) signed by the subject or legally acceptable representative.
- Clinical diagnosis of dementia due to possible or probable Alzheimer's disease
- Mini-Mental State Examination score >= 16 and <= 24 at screening
- If female, postmenopausal for at least 1 year
Key exclusion criteria (39 listed)
- Exposure to an experimental drug, experimental biologic or experimental medical device within the longer of 5 half-lives or 3 months before screening
- Residence in a skilled nursing facility
- Clinically significant laboratory test results
- Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating hormone level and thyroid supplementation dose must be stable for at least 6 months before screening)
- Insufficiently controlled diabetes mellitus or requiring insulin
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PTI-125, 100 mg tabletsPTI-125, 100 mg tablets taken twice a day for 28 days | Drug | Simufilam (PTI-125) |
Primary outcome
Maximum Plasma Concentration (Cmax)
Time frame: 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.
Time to Maximum Plasma Concentration (Tmax)
Time frame: 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
Last Quantifiable Plasma Concentration (Clast)
Time frame: 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.
Time to Last Quantifiable Plasma Concentration (Tlast)
Time frame: 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.
Area Under the Curve (AUClast)
Time frame: 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.
Plasma Half-life (T1/2)
Time frame: 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
2 secondary outcomes
SavaDx (Biomarker)
Time frame: Study Day 1 and Day 28
CSF Biomarkers
Time frame: Change from Baseline to Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28438486Wang HY, Lee KC, Pei Z, Khan A, Bakshi K, Burns LH. PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis. Neurobiol Aging. 2017 Jul;55:99-114. doi: 10.1016/j.neurobiolaging.2017.03.016. Epub 2017 Mar 31.
- Background: PubMed 22815492Wang HY, Bakshi K, Frankfurt M, Stucky A, Goberdhan M, Shah SM, Burns LH. Reducing amyloid-related Alzheimer's disease pathogenesis by a small molecule targeting filamin A. J Neurosci. 2012 Jul 18;32(29):9773-84. doi: 10.1523/JNEUROSCI.0354-12.2012.
- Results publication: PubMed 32920628Wang HY, Pei Z, Lee KC, Lopez-Brignoni E, Nikolov B, Crowley CA, Marsman MR, Barbier R, Friedmann N, Burns LH. PTI-125 Reduces Biomarkers of Alzheimer's Disease in Patients. J Prev Alzheimers Dis. 2020;7(4):256-264. doi: 10.14283/jpad.2020.6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lindsay Burns, PhD study director
Cassava Sciences, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PTI-125, 100 mg tablets in people with Alzheimer Disease, run by Pain Therapeutics at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Plasma Concentration (Cmax) (time frame: 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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03748706, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2021.