A Safety Study of PTI-125 in Healthy Volunteers

A Phase I, Single Center, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose, Pharmacokinetic and Safety Study of PTl-125 in Healthy Volunteers

This was a Phase I, single center, randomized, double-blind, placebo-controlled, single ascending dose (SAD) study in healthy volunteers, 18 to 45 years of age. A total of twenty-four (24) subjects were enrolled into the study in one of three dose cohorts. Each cohort contained eight subjects; six subjects received PTI-125 and two received placebo. Three doses of PTI-125 oral solution (50, 100, and 200 mg) or placebo solution were administered to respective cohorts.

The study included a screening period (Day -28 to Day -1), an inpatient treatment period (Day 0 through Day 4), and a follow-up visit (Day 7). Subjects reported to the clinic on the day before dosing and were randomized to receive either a single dose of orally administered PTI-125 or placebo. Each dose was administered following an overnight fast of at least 10 hours.

For each dose level, dosing was staggered such that two subjects (one active and one placebo) were dosed prior to the rest of the group. After a minimum of 24 hours and review of all 24-hour safety assessments (electrocardiogram \[ECG\], a brief physical examination, vital signs, and laboratory assessments) an independent Data Safety Monitoring Board/Data Monitoring Committee (DSMB/DMC) determined whether the remaining 6 subjects were to be dosed.

Pharmacokinetic blood samples were obtained prior to dosing and at specified intervals during the study (0-72 hours post-dose). Blood draws for laboratory testing were performed prior to dosing and at 24 hours post dose. After safety assessments of ECG, vital signs, and a brief physical exam at 72 hours, subjects were discharged from the clinic and returned 7 days post-dose for a final safety assessment.

Eligibility Criteria:
Inclusion Criteria:

* Male or female subjects between 18 and 45 years of age, inclusive.
* The subject has a body mass index (BMI) within 18-30 kg/m2 (inclusive).
* The subject is in good health as determined by medical history and physical examination and clinical laboratory parameters.
* The subject is willing and able to speak, read, and understand English and provide written informed consent.
* The subject is a non-smoker for at least 12 months. If a former smoker, the reason for stopping must be evaluated.
* Females who are physically incapable of childbearing defined as postmenopausal, or surgically sterile (hysterectomy, bilateral tubal ligation, bilateral oophorectomy or an Essure procedure). Appropriate documentation (ex; medical record) of the surgical sterilization procedure to be obtained and held within the subject's study file.
* The subject must agree to comply with the drawing of blood samples for the PK assessments.
* The subject is willing and able to comply with all testing and requirements defined in the protocol.
* The subject is willing and able to remain at the study site unit for the duration of the confinement period and return for the outpatient visit.

Exclusion Criteria:

* The subject has any relevant deviations from normal in physical examination, electrocardiogram (ECG), or clinical laboratory tests, as evaluated by the investigator.
* The subject has had a clinically significant illness within 30 days of Check-in.
* The subject has a history of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease.
* The subject has used any prescription medication within 14 days of dosing or overthe- counter (OTC) medication within 48 h of dosing or intends to use any prescription medication or OTC medication during the study that may interfere with the evaluation of study medication.
* The subject has used alcohol, caffeine or xanthine-containing products 48 h before dosing or intends to use any of these products during the study.
* The subject has used grapefruit, grapefruit juice, or grapefruit-containing products days before dosing or intends to use any of these products during the study.
* The subject has a history of substance abuse or a positive ethanol breath test, urine cotinine, or urine drug screen at screening or at check-in. The subject has a positive serum hepatitis B surface antigen or positive HCV antibody test at the Screening Visit.
* The subject has a positive HIV test at the Screening Visit.
* Female subject is pregnant or breastfeeding.
* The subject has received an investigational drug within 30 days of Check-in.
* The subject has donated or lost a significant volume of blood (\>450 mL) within 4 weeks prior to the study.
* The subject is unwilling to reside in the study unit for the duration of the study or to cooperate fully with the investigator or site personnel.
* The subject has an AST/ALT or total bilirubin greater than the ULN. One repeat test will be allowed.