Safety, Pharmacokinetics, and Food Effect of PS1 in Healthy Subjects
Study Details
Study Description
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), and food effect of PS1 in healthy subjects.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
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, and food effect 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-100 mg (Cohort 1), 200 mg (Cohort 2), and 400 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 14 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 100 mg PS1 or Placebo tablets in a fasted condition on Day 1 and be followed for 14 days.
Two cohorts are assigned in the MAD portion: 50 mg/day (Cohort 5) and 100 mg/day (Cohort 6). Only the dose level of MAD lower than the maximum tolerated dose (MTD) of SAD portion can be activated (If 100 mg was determined as the MTD of SAD, only cohort 5 could be activated). An eligible subject will receive PS1 or Placebo tablets once daily in a fed condition for 28 days and be followed for additional 14 days.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: SAD portion - Cohort 1 (100mg) An eligible subject will receive a single dose of 100 mg of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 14 days. |
Drug: PS1
PS1 will be provided as a 120 mg tablet with 25 mg active pharmaceutical ingredient
Other Names:
Drug: Placebo
Placebo
|
Experimental: SAD portion - Cohort 2 (200mg) An eligible subject will receive a single dose of 200 mg of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 14 days. |
Drug: PS1
PS1 will be provided as a 120 mg tablet with 25 mg active pharmaceutical ingredient
Other Names:
Drug: Placebo
Placebo
|
Experimental: SAD portion - Cohort 3 (400mg) An eligible subject will receive a single dose of 400 mg of PS1 or Placebo tablets in a fed condition on Day 1 and be followed for 14 days. |
Drug: PS1
PS1 will be provided as a 120 mg tablet with 25 mg active pharmaceutical ingredient
Other Names:
Drug: Placebo
Placebo
|
Experimental: FE portion - Cohort 4 (100mg) An eligible subject will receive a single dose of 100 mg PS1 or Placebo tablets in a fasted condition on Day 1 and be followed for 14 days. |
Drug: PS1
PS1 will be provided as a 120 mg tablet with 25 mg active pharmaceutical ingredient
Other Names:
Drug: Placebo
Placebo
|
Experimental: MAD portion - Cohort 5 (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 14 days. |
Drug: PS1
PS1 will be provided as a 120 mg tablet with 25 mg active pharmaceutical ingredient
Other Names:
Drug: Placebo
Placebo
|
Experimental: MAD portion - Cohort 6 (100mg) An eligible subject will receive 100 mg PS1 or Placebo tablets once daily in a fed condition for 28 days and be followed for additional 14 days. |
Drug: PS1
PS1 will be provided as a 120 mg tablet with 25 mg active pharmaceutical ingredient
Other Names:
Drug: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Incidence of dose-limiting toxicity (DLT) during the DLT observation period [Day 1~ Day 8 (SAD cohort); Day 1~ Day 36 (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 Outcome Measures
- Incidence of adverse events (AEs) and serious adverse events (SAEs) [SAD, FE: up to 4 weeks; MAD: up to 8 weeks]
All adverse events (AEs) will be assessed for severity by the investigator based on NCI-CTCAE v5.0
- Number of participants with abnormalities in Vital signs [SAD, FE: Baseline,1~2 weeks; MAD: Baseline,1~6 weeks]
Number of participants with abnormal systolic/diastolic blood pressure (in mmHg), respiratory rate, pulse rate (in beat per minute, bpm), and body temperature (in ℃)
- Number of participants with abnormalities in Laboratory examinations [SAD, FE: Baseline,1~2 weeks; MAD: Baseline,1~6 weeks]
Number of participants with abnormal Hematology (hemoglobin, hematocrit, RBC, platelet, WBC, WBC differentials (neutrophils, eosinophils, basophils, lymphocytes, monocytes), MCV, MCH, MCHC), biochemistry (HbA1c, fasting plasma glucose, albumin, alkaline phosphatase, ALT, AST, BUN, creatinine, cholestero1, γ-GT, total protein, total bilirubin, direct bilirubin, triglyceride, amylase, lipase, calcium, sodium, potassium, chloride), and urinalysis (pH, protein, glucose, bilirubin, urobilinogen, ketone body, specific gravity, occult blood, RBC, WBC, creatinine, ratio of albumin/creatinine) results
- Acute kidney injury (AKI) marker - NGAL [SAD, FE: Baseline, 1~2 weeks; MAD: Baseline, 1~6 weeks]
Urine samples will be collected for analyzing acute kidney injury (AKI) markers
- Acute kidney injury (AKI) marker - KIM-1 [SAD, FE: Baseline, 1~2 weeks; MAD: Baseline, 1~6 weeks]
Urine samples will be collected for analyzing acute kidney injury (AKI) markers
- Number of participants with abnormalities in 12-lead electrocardiogram (EKG) [SAD, FE: Baseline, 1~2 weeks; MAD: Baseline, 1~6 weeks]
Number of participants with abnormal Ventricular rate, PR interval, QRS interval, and QT interval
- Number of participants with abnormalities in Physical examination [SAD, FE: Baseline, 1~2 weeks; MAD: Baseline, 1~6 weeks]
Number of participants with abnormal Physical examination results, including general appearance, skin, eyes, ears, nose, throat, head and neck (including thyroid), heart, chest and lungs, abdomen, extremities, lymph nodes, musculoskeletal, neurological system, and other body systems
- Pharmacokinetics of PS1 - AUC [Day 1 and 2 (SAD, FE and MAD portion), Day 28 and 29 (MAD portion only)]
Area under the serum concentration-time profile
- Pharmacokinetics of PS1 - Cmax [Day 1 and 2 (SAD, FE and MAD portion), Day 28 and 29 (MAD portion only)]
The peak post-dose concentration
- Pharmacokinetics of PS1 - Tmax [Day 1 and 2 (SAD, FE and MAD portion), Day 28 and 29 (MAD portion only)]
Time at which Cmax is observed
- Pharmacokinetics of PS1 - T1/2 [Day 1 and 2 (SAD, FE and MAD portion), Day 28 and 29 (MAD portion only)]
Terminal phase elimination half-life
- Pharmacokinetics of PS1 - MRT [Day 1 and 2 (SAD and FE portion only)]
Mean Residence Time
- Pharmacokinetics of PS1 - CL/F [Day 1 and 2 (SAD and FE portion only)]
Apparent Clearance
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Both genders aged 20 to 80 years, inclusive at screening
-
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% at Screening
-
Fasting plasma glucose < 110 mg/dL at Screening
-
Body mass index (BMI) between 18.5 and 28.0 kg/m2
-
Negative test for hepatitis B surface antigen (HBsAg), Anti-HCV antibody, or human immunodeficiency virus (HIV) at screening
-
Is willing to comply with the trial restrictions
-
Able to understand and sign the informed consent form
Exclusion Criteria:
-
History of diabetes mellitus
-
Under the systemic treatment of any prescription medication or over-the-counter (OTC) medication within 7 days before Screening
-
Received any vaccination within 14 days before Screening
-
Known hypersensitivity to any of the components of PS1 tablet
-
History of clinically significant hematological, renal, endocrine, pulmonary, 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 cancer (malignancy) or have ever received any anti-cancer therapy
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Regular smoker
-
Consumed greater than 3 glasses of alcoholic beverages per day for the past 4 weeks before Screening
-
Received any investigational therapy from another clinical study, performed any major surgeries, or took glucose-lowering medications within the last 12 weeks prior to Screening
-
Received any systemic steroids (inhaled and intranasal steroids are permitted) or other immunosuppressive medications within 4 weeks prior to Screening
-
Have ever received cell therapy or organ transplantation
-
Other conditions not suitable for participating in this study as judged by the investigator
-
Any conditions that forbid the completion of study procedures due to the local regulatory restrictions
-
Female subject of childbearing potential who:
Is lactating; or Has a positive pregnancy test result from signing informed consent to the end of the study; or Refuses to adopt at least one form of birth control (refer to Section 5.3) from signing informed consent to the end of the study.
- Male subject with a female spouse/partner who is of childbearing potential refuses to adopt at least one form of birth control (refer to Section 5.3) from signing informed consent to the end of the study.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Pharmasaga Co. Ltd.
Investigators
- Principal Investigator: Yi-Cheng Chang, MD., PhD, National Taiwan University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PS1-01