Safety, Pharmacokinetics, and Food Effect of PS1 in Subjects

NCT05176210 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PS1-01
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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.

Conditions

Type II Diabetes

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicity (DLT) during the DLT observation period and the maximum tolerated dose (MTD) of PS1

  Dose escalation will be terminated based on the following criteria: \- Among the six subjects who received PS1 in a cohort, more than one subject experienced DLT(s). MTD will basically be declared as the highest dose level at which ≤1/6 of PS1-treated subjects in a cohort experienced DLT(s). 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 3 days\* \* Note: For Cohorts 7 and 8, AEs requiring specific definitions will be referenced under the heading 'For MAD cohorts (Cohorts 7 and 8)' below, while the remaining AEs will be followed the standard procedures outlined herein. that occurs in the DLT observation period and is causally related (possibly, probably, or definitely related) to the test article judged by the investigator.

  DLT observation period: from Day 1 to EOS - For SAD and FE cohorts in healthy subjects: from Day 1 to Day 8±1 - For MAD cohorts in T2DM patients: from Day 1 to Day 35±1

Secondary Outcomes (30)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  SAD, FE in healthy volunteers: Approximately 3 weeks; SAD in T2DM subjects: Approximately 4 weeks; MAD in T2DM subjects: Approximately 7 weeks

• Changes in vital signs (Systolic Blood Pressure & Diastolic Blood Pressure) at each post-treatment measurement from baseline

  SAD, FE in healthy volunteers: Approximately 3 weeks; SAD in T2DM subjects: Approximately 4 weeks; MAD in T2DM subjects: Approximately 7 weeks

• Changes in Laboratory examinations - Hematology (Hemoglobin and mean corpuscular hemoglobin concentration, MCHC) at each post-treatment measurement from baseline

  SAD, FE in healthy volunteers: Approximately 3 weeks; SAD in T2DM subjects: Approximately 4 weeks; MAD in T2DM subjects: Approximately 7 weeks

• Changes in acute kidney injury (AKI)-NGAL markers at each post-treatment measurement from baseline

  SAD, FE in healthy volunteers: Approximately 3 weeks; SAD in T2DM subjects: Approximately 4 weeks; MAD in T2DM subjects: Approximately 7 weeks

• Changes in 12-lead electrocardiogram (EKG) (PR interval, QRS interval, and QT interval) at each post-treatment measurement from baseline

  SAD, FE in healthy volunteers: Approximately 3 weeks; SAD in T2DM subjects: Approximately 4 weeks; MAD in T2DM subjects: Approximately 7 weeks

Other Outcomes (1)

• Exploratory Endpoints (For MAD only)

  MAD in T2DM subjects: Approximately 7 weeks

Study Arms (8)

SAD portion - Cohort 1 (25mg)

EXPERIMENTAL

An eligible healthy subject will receive a single dose of 25 mg of PS1 or Placebo tablet in a fed condition on Day 1 and be followed for 7 days.

Drug: PS1; Drug: Placebo

SAD portion - Cohort 2 (50mg)

EXPERIMENTAL

An eligible healthy 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.

Drug: PS1; Drug: Placebo

SAD portion - Cohort 3 (75mg)

EXPERIMENTAL

An eligible healthy 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.

Drug: PS1; Drug: Placebo

FE portion - Cohort 4 (50mg)

EXPERIMENTAL

An eligible healthy 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.

Drug: PS1; Drug: Placebo

SAD portion - Cohort A (25mg)

EXPERIMENTAL

An eligible T2DM subject will receive 25 mg PS1 tablet once daily in a fed condition for 1 day and be followed for additional 14 days.

Drug: PS1; Drug: Placebo

SAD portion - Cohort B (50mg)

EXPERIMENTAL

An eligible T2DM subject will receive 50 mg PS1 tablets once daily in a fed condition for 1 day and be followed for additional 14 days.

Drug: PS1; Drug: Placebo

MAD portion - Cohort 7 (25mg)

EXPERIMENTAL

An eligible subject will receive 25 mg PS1 or Placebo tablet once daily in a fed condition for 28±1 days and be followed for additional 7 days.

Drug: PS1; Drug: Placebo

MAD portion - Cohort 8 (50mg)

EXPERIMENTAL

An eligible subject will receive 50 mg PS1 or Placebo tablets once daily in a fed condition for 28±1 days and be followed for additional 7 days.

Drug: PS1; Drug: Placebo

Interventions

PS1 DRUG

PS1 will be provided as a 120 mg tablet with 25 mg active pharmaceutical ingredient.

FE portion - Cohort 4 (50mg); MAD portion - Cohort 7 (25mg); MAD portion - Cohort 8 (50mg); SAD portion - Cohort 1 (25mg); SAD portion - Cohort 2 (50mg); SAD portion - Cohort 3 (75mg); SAD portion - Cohort A (25mg); SAD portion - Cohort B (50mg)

Placebo DRUG

Placebo will be provided as a 120 mg tablet.

FE portion - Cohort 4 (50mg); MAD portion - Cohort 7 (25mg); MAD portion - Cohort 8 (50mg); SAD portion - Cohort 1 (25mg); SAD portion - Cohort 2 (50mg); SAD portion - Cohort 3 (75mg); SAD portion - Cohort A (25mg); SAD portion - Cohort B (50mg)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. Subjects with positive anti-HCV may be enrolled only if they have a negative HCV RNA result during the screening period.
• Is willing to follow the trial life style instruction and protocol procedure
• Able to understand and sign the informed consent form
• 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/1.73m2
• Diagnosis of T2DM
• T2DM treated with diet and exercise alone currently, for at least 2 weeks prior to Screening
• With HbA1c level between 5.7% to 9.0% or fasting plasma glucose level between 100 mg/dL to 250 mg/dL at Screening
• With estimated glomerular filtration rate (eGFR) \> 60 ml/min /1.73m2
• Patients taking medications for T2DM comorbidities, i.e., hypertriglyceridemia, hyperlipidemia, and hypertension, should be on a stable dose of their medication for at least 3 months prior to Screening. Any other chronic medications should be on a stable dose for at least 4 weeks prior to Screening.

You may not qualify if:

• 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-other than T2DM and its comorbidities (i.e., hypertriglyceridemia, hyperlipidemia, and hypertension)
• History of pancreatitis
• Serum amylase \> 1.5 × Upper Limit of Normal (ULN) or lipase \> 1.5 × ULN
• Clinically significant ECG abnormality at Screening
• History of cancer (malignancy) or have ever received any anti-cancer therapy
• Regular smoker Regular smoker is defined as who smokes every day (≥ 1 cigarette/day in average in the past 8 weeks of Screening)
• Consumed greater than 3 units of alcoholic beverages per day in average for the past 4 weeks before Screening One unit is equivalent to one can of beer (\<10% alcohol; about 330 mL), one glass of wine (10\~20% alcohol; about 150 mL), or one shot of distilled spirits (\>20% alcohol; about 45 mL)
• Received any investigational therapy from another clinical study or underwent any major surgeries within the last 12 weeks prior to Screening
• Took glucose-lowering medications within the last 2 weeks prior to Screening

Sponsors & Collaborators

• Pharmasaga Co. Ltd.: lead

Study Sites (1)

Mingche Liu

Taipei, Taiwan

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Mingche Liu, MD., PhD

  Taipei Medical University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: An "open-labeled" study design will be applied for the SAD portion for T2DM patients with two SAD dose cohorts-25 mg (Cohort A) and 50 mg (Cohort B).

Study Record Dates

• First Submitted: November 29, 2021
• First Posted: January 4, 2022
• Study Start: December 22, 2023
• Primary Completion: April 27, 2026
• Study Completion: June 5, 2026
• Last Updated: July 7, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)