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Open-label, PK and Safety Study in Mild-to-moderate Alzheimer's Disease Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03748706
Recruitment Status : Recruiting
First Posted : November 21, 2018
Last Update Posted : November 21, 2018
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Pain Therapeutics

Tracking Information
First Submitted Date  ICMJE November 13, 2018
First Posted Date  ICMJE November 21, 2018
Last Update Posted Date November 21, 2018
Estimated Study Start Date  ICMJE November 2018
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2018)
  • Maximum Plasma Concentration (Cmax) [ Time Frame: Study Days 1, 2, 28 and 29 ]
    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 Days 1, 2, 28 and 29 ]
    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, 2, 28 and 29 ]
    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 Days 1, 2, 28 and 29 ]
    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 (AUC) [ Time Frame: Study Days 1, 2, 28 and 29 ]
    AUC for PTI-125 plasma concentration from time zero to the last quantifiable plasma concentration.
  • Minimum Plasma Concentration (Cmin) [ Time Frame: Study Days 7 and 14 ]
    Assessment of the lowest plasma concentration of PTI-125
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2018)
  • PTI-125DX (biomarker) [ Time Frame: Study Days 1, 7, 14 and 29 ]
    Blood samples will be tested for the companion dignostic/biomarker for Alzheimer's disease.
  • Biomarker assay [ Time Frame: Day 28 ]
    A CSF sample collection will be performed for Aβ/tau, YKL40 and other potential CSF biomarkers
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Open-label, PK and Safety Study in Mild-to-moderate Alzheimer's Disease Patients
Official Title  ICMJE A Phase 2a, Open-label, Multiple Dose, Safety, Pharmacokinetic and Biomarker Study of PTl-125 in Mild-to-moderate Alzheimer's Disease Patients
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE Drug: PTI-125
Oral 100 mg tablet
Study Arms  ICMJE Experimental: PTI-125
PTI-125 100 mg oral tablets administered twice daily (BID)
Intervention: Drug: PTI-125
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 18, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2019
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ages ≥ 50 and ≤ 85 years
  • Informed consent form (ICF) signed by the subject or legally acceptable representative. If a legally acceptable representative signs the ICF, a notation of capacity of the subject must be noted.
  • Clinical diagnosis of dementia due to possible or probable AD consistent with criteria established by a workgroup of the National Institute on Aging and the Alzheimer's Disease Association.
  • MMSE 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-h) 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 for the PK assessments, laboratory assessments and PTI-125DX and with a lumbar puncture and the drawing of CSF samples for biomarker assessments.
  • The patient has an Aβ/tau Index in CSF that indicates AD. This value (total tau/Aβ42) will be ≥ 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 ULN.
  • 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 QTc 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 AD (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)
  • Wernicke's encephalopathy
  • Active acute or chronic CNS infection
  • Donepezil 23 mg or greater QD 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. PTI-125 is a marginal/weak inhibitor of the multidrug and toxin extrusion protein 1 (MATE1) transporter.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael R Marsman, PharmD 5125822173
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03748706
Other Study ID Numbers  ICMJE PTI-125-03
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Pain Therapeutics
Study Sponsor  ICMJE Pain Therapeutics
Collaborators  ICMJE National Institutes of Health (NIH)
Investigators  ICMJE Not Provided
PRS Account Pain Therapeutics
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP