A Phase I, Double-Blind, Placebo-Controlled, Randomized, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Food Effect and Potential Efficacy of PS1 in Subjects
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Type II Diabetes
- Sponsor
- Pharmasaga Co. Ltd.
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- Incidence of dose-limiting toxicity (DLT) during the DLT observation period
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a phase I, double-blind, placebo-controlled, randomized, single- and multiple-ascending dose study to evaluate new study intervention, PS1. PS1 is a potential blood glucose control medication, which is developed by Pharmasaga Co. Ltd. planned for treating type II diabetes mellitus (T2DM). This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), food effect and potential efficacy of PS1 in subjects.
Detailed Description
This first-in-human Phase I study consists of a single ascending-dose (SAD) portion, a food effect (FE) portion, and a multiple ascending-dose (MAD) portion, aiming to evaluate the safety, tolerability, pharmacokinetics, food effect and potential efficacy of PS1 in healthy subjects. A randomized, double-blinded, placebo-controlled study design will be applied for the SAD portion with three SAD dose cohorts-25 mg (Cohort 1), 50 mg (Cohort 2), and 75 mg (Cohort 3). An eligible subject in this portion will receive a single dose of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 7 days. In FE portion, only one cohort (Cohort 4) is assigned. The FE cohort (Cohort 4) will use the same study design as the SAD cohorts. An eligible subject in this portion will receive a single dose of 50 mg PS1 or Placebo tablets in a fasted condition on Day 1 and be followed for 7 days. Four cohorts are assigned in the MAD portion: 25 mg/day (Cohort 5 \& 7) and 50 mg/day (Cohort 6 \& 8) in healthy volunteers and participants respectively. Only the dose level of MAD lower than the maximum tolerated dose (MTD) of SAD portion can be activated (If 50 mg was determined as the MTD of SAD, only cohort 5 \& 7 could be activated). An eligible subject will receive PS1 or Placebo tablets once daily in a fed condition for 14 days \& 28 days in healthy volunteers and participants respectively and be followed for additional 7 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For all cohorts, a subject is eligible for the study if all of the following apply:
- •Both genders aged 18 to 80 years, inclusive at screening
- •Body mass index (BMI) between 18.5 and 40.0 kg/m2
- •Negative test for hepatitis B surface antigen (HBsAg), Anti-HCV antibody, and human immunodeficiency virus (HIV) at screening
- •Is willing to follow the trial life style instruction and protocol procedure
- •Able to understand and sign the informed consent form.
- •Inclusion criteria applied for healthy subjects (Cohorts 1\~6)
- •Overtly healthy subject, who is considered to be generally healthy based on medical history, vital signs, laboratory tests, 12-lead EKG, and physical examination, as judged by the investigator
- •With HbA1c value of \< 6.5% and fasting plasma glucose \< 110 mg/dL at Screening
- •With estimated glomerular filtration rate (eGFR) \> 80 ml/min
Exclusion Criteria
- •For all cohorts, a subject meeting any of the following exclusion criteria will be excluded from study participation.
- •History of Type I diabetes mellitus
- •Under the systemic treatment of any prescription medication or over-the-counter (OTC) medication that may interfere with the safety or PK assessment judged by the investigator within 7 days before Screening
- •Received strong CYP enzyme inhibitor or inducer within 14 days before Screening
- •Received any vaccination within 14 days before Screening
- •Has required insulin therapy within the past 12 weeks
- •Known hypersensitivity to any of the components of PS1 tablet
- •History of major clinically significant hematological, renal, respiratory, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, musculoskeletal, immune, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing) within 3 months of Screening that may significantly alter the biomarker panel, require receiving any systemic medications, or interfere with the interpretation of data, as judged by the investigator
- •History of pancreatitis
- •Serum amylase \> 1.5 × Upper Limit of Normal (ULN) or lipase \> 1.5 × ULN
Arms & Interventions
SAD portion - Cohort 2 (50mg)
An eligible subject will receive a single dose of 50 mg of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 7 days.
Intervention: Placebo
SAD portion - Cohort 1 (25mg)
An eligible subject will receive a single dose of 25 mg of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 7 days.
Intervention: PS1
SAD portion - Cohort 1 (25mg)
An eligible subject will receive a single dose of 25 mg of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 7 days.
Intervention: Placebo
SAD portion - Cohort 2 (50mg)
An eligible subject will receive a single dose of 50 mg of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 7 days.
Intervention: PS1
SAD portion - Cohort 3 (75mg)
An eligible subject will receive a single dose of 75 mg of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 7 days.
Intervention: PS1
SAD portion - Cohort 3 (75mg)
An eligible subject will receive a single dose of 75 mg of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 7 days.
Intervention: Placebo
FE portion - Cohort 4 (50mg)
An eligible subject will receive a single dose of 50 mg PS1 or Placebo tablets in a fasted condition on Day 1 and be followed for 7 days.
Intervention: PS1
FE portion - Cohort 4 (50mg)
An eligible subject will receive a single dose of 50 mg PS1 or Placebo tablets in a fasted condition on Day 1 and be followed for 7 days.
Intervention: Placebo
MAD portion - Cohort 5 (25mg)
An eligible subject will receive 25 mg PS1 or Placebo tablets once daily in a fed condition for 14 days and be followed for additional 7 days.
Intervention: PS1
MAD portion - Cohort 5 (25mg)
An eligible subject will receive 25 mg PS1 or Placebo tablets once daily in a fed condition for 14 days and be followed for additional 7 days.
Intervention: Placebo
MAD portion - Cohort 6 (50mg)
An eligible subject will receive 50 mg PS1 or Placebo tablets once daily in a fed condition for 14 days and be followed for additional 7 days.
Intervention: PS1
MAD portion - Cohort 6 (50mg)
An eligible subject will receive 50 mg PS1 or Placebo tablets once daily in a fed condition for 14 days and be followed for additional 7 days.
Intervention: Placebo
MAD portion - Cohort 7 (25mg)
An eligible subject will receive 25 mg PS1 or Placebo tablets once daily in a fed condition for 28 days and be followed for additional 7 days.
Intervention: PS1
MAD portion - Cohort 7 (25mg)
An eligible subject will receive 25 mg PS1 or Placebo tablets once daily in a fed condition for 28 days and be followed for additional 7 days.
Intervention: Placebo
MAD portion - Cohort 8 (50mg)
An eligible subject will receive 50 mg PS1 or Placebo tablets once daily in a fed condition for 28 days and be followed for additional 7 days.
Intervention: PS1
MAD portion - Cohort 8 (50mg)
An eligible subject will receive 50 mg PS1 or Placebo tablets once daily in a fed condition for 28 days and be followed for additional 7 days.
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of dose-limiting toxicity (DLT) during the DLT observation period
Time Frame: Day 1~ Day 8 (SAD cohort); Day 1~ Day 35 (MAD cohort)
DLT is defined as: (1) any adverse event (AE) ≥ Grade 3 (CTCAE v5.0) or (2) Grade 2 AE that does not resolve to grade 1 or less within 72 hours, that occurs in the DLT observation period and is causally related (possibly, probably, or definitely related) to the test article judged by the investigator.
Secondary Outcomes
- Incidence of adverse events (AEs) and serious adverse events (SAEs)(SAD, FE: up to 4 weeks; MAD: up to 8 weeks)
- Number of participants with abnormalities in Vital signs(SAD, FE: Baseline,1~2 weeks; MAD: Baseline,1~6 weeks)
- Acute kidney injury (AKI) marker(SAD, FE: Baseline, 1~2 weeks; MAD: Baseline, 1~6 weeks)
- Number of participants with abnormalities in Physical examination(SAD, FE: Baseline, 1~2 weeks; MAD: Baseline, 1~6 weeks)
- Number of participants with abnormalities in 12-lead electrocardiogram (EKG)(SAD, FE: Baseline, 1~2 weeks; MAD: Baseline, 1~6 weeks)
- Exploratory Endpoints (For MAD only)(MAD: Baseline, 1~6 weeks)
- Potential efficacy (For Cohort 7 and 8 only)(MAD: Baseline, 1~6 weeks)
- Number of participants with abnormalities in Laboratory examinations(SAD, FE: Baseline,1~2 weeks; MAD: Baseline,1~6 weeks)
- Pharmacokinetics (PK) of PS1(Day 1 and 2 (SAD, FE and MAD portion), Day 28 and 29 (MAD portion only))