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

A Phase 2a, Open-label, Multiple Dose, Safety, Pharmacokinetic and Biomarker Study of PTl-125 in Mild-to-moderate Alzheimer's Disease Patients

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03748706

Enrollment

Registered

2018-11-21

Start date

2019-03-07

Completion date

2019-05-08

Last updated

2021-07-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alzheimer Disease

Brief summary

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.

Interventions

DRUGPTI-125, 100 mg tablets

PTI-125, 100 mg tablets taken twice a day for 28 days

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

50 Years to 85 Years

Healthy volunteers

Inclusion criteria

* 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 * 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.

Exclusion criteria

* 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) * 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.

Design outcomes

Primary

Measure	Time frame	Description
Plasma Half-life (T1/2)	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
Time to Last Quantifiable Plasma Concentration (Tlast)	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)	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.
Maximum Plasma Concentration (Cmax)	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)	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)	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.

Secondary

Measure	Time frame	Description
CSF Biomarkers	Change from Baseline to Day 28	A cerebrospinal fluid sample collection will be performed for Aβ42, tau, YKL40 and other potential CSF biomarkers
SavaDx (Biomarker)	Study Day 1 and Day 28	Blood samples will be tested for the complementary diagnostic/biomarker for Alzheimer's disease.

Countries

United States

Participant flow

Participants by arm

Arm	Count
PTI-125 PTI-125 100 mg oral tablets administered twice daily (BID) PTI-125, 100 mg tablets: PTI-125, 100 mg tablets taken twice a day for 28 days	13
Total	13

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	1

Baseline characteristics

Characteristic	PTI-125
Age, Continuous	67.8 Years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	10 Participants
Region of Enrollment United States	13 Participants
Sex: Female, Male Female	9 Participants
Sex: Female, Male Male	4 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 13
other Total, other adverse events	1 / 13
serious Total, serious adverse events	0 / 13