Overview
This is a randomized, double-blind, placebo-controlled phase I study to evaluate the safety, tolerability and PK profiles of orally administered VG290131 in healthy subjects. The main questions it aims to answer are:
- The safety and tolerability of VG290131 when administered orally as a single dose and multiple doses in healthy subjects.
- The pharmacokinetic (PK) profiles of VG290131 and the food effect on the PK profiles of VG290131 in healthy subjects.
Approximately 86 subjects will be enrolled in the study.
Eligibility
Inclusion Criteria:
A subject will be eligible for inclusion in this study only if all of the following
criteria are met:
1. Willing to comply with protocol required visit schedule and visit requirements and
provide written ICF;
2. Healthy adult male and female subjects, aged 18 to 45 years of age (inclusive) at the
time of signing the ICF;
3. Body mass index between 18.0 and 32.0 kg/m2, inclusive;
4. Considered medically healthy as determined by the investigator, based on medical
history and clinical evaluations including physical examination, clinical laboratory
tests, vital sign measurements, and 12-Lead ECG;
5. Male subjects must agree to practice true abstinence; be surgically sterilized
(performed at least 6 months prior to screening and documented to no longer produce
sperm - verbal confirmation through medical history review acceptable); or agree to
use a condom plus effective contraception methods for their female partner, if of
childbearing potential, from the signing of ICF to 3 months after the last dose of
IMPs and refrain from donating sperm during this period. These contraception
requirements do not apply if the male subject is in an exclusively same sex
relationship;
6. Female subjects are eligible to participate if they are not pregnant, not
breastfeeding, and at least 1 of the following conditions applies:
- Women of non-childbearing potential (WONCBP), defined as surgically sterile
(hysterectomy, bilateral salpingectomy, bilateral tubal ligation or bilateral
oophorectomy - verbal confirmation through medical history review acceptable) or
postmenopausal (no menses for 12 months and confirmed by follicle stimulating
hormone [FSH] level ≥40 mlU/mL);
- WOCBP and agree to practice true abstinence or agrees to use a highly effective
method of contraceptions consistently from the signing of ICF to 3 months after
the last dose of investigational medicinal products [IMPs] and refrain from
donating eggs during this period. And WOCBP must have a negative serum and/or
urine pregnancy test result within 7 days prior to the first dose of IMPs.
- Subject is in an exclusively same-sex relationship.
Exclusion Criteria:
A subject meeting any of the following exclusion criteria will not be allowed to
participate in this study:
1. Ascertained or presumptive hypersensitivity (including allergies) to any ingredient of
the VG290131; history of other significant allergies or anaphylaxis, as determined by
the investigator;
2. Considered by the investigator to be ineligible for the study due to a history of or
current condition of significant metabolic or endocrine, hepatic, renal,
hematological, pulmonary, cardiovascular, gastrointestinal, urological, immunological,
neurological, or psychiatric disorders with clinical manifestations;
3. Active or history of serious mental illness or psychiatric disorder, including but not
limited to schizophrenia, bipolar disorder, or severe depression, which require
current pharmacological intervention;
4. History of stomach or intestinal surgery or resection diseases including but not
limited to, gastric band/gastric resection and/or intestinal resection and/or duodenal
disease (i.e. celiac disease) which may potentially alter absorption and/or excretion
of VG290131 (except for an appendectomy);
5. Used drugs or substances known to be inducers or inhibitors of cytochrome P450 enzymes
or P-glycoprotein (P-gp) substrates within 28 days or 5 half-lives (whichever is
longer) prior to the first dose of IMPs;
6. Used prescription or over-the-counter (OTC) drugs (with the exception of hormonal
contraception, menopausal hormone replacement therapy or occasional analgesics such as
Paracetamol [1 g per dose and maximum 2-4 g per day], Ibuprofen and standard daily
vitamins etc. in short term at the Investigator's discretion), within 14 days or 5
half-lives (whichever is longer) prior to the first dose of IMPs;
7. Participated in any other investigational trials or has been exposed to other
investigational drugs within 28 days or 5 half-lives of the previously administered
investigational drug, whichever is longer, prior to the first dose of IMPs;
8. Smoking ≥ 5 cigarettes per day (or an equivalent amount of any other
nicotine-containing products) within 6 months before screening or unable to stop
smoking during the study;
9. Alcohol consumption of > 21 units per week for males and > 14 units per week for
females within the 6 months before screening (1 unit=360 mL of beer or 45 mL of
spirits with an alcohol content of ≥ 40% or 150 mL of wine) or a positive result of
alcohol breath test on admission or unable to abstain from consuming alcohol from 24 h
prior to admission, until completion of the end of study (EOS) visit;
10. History of drug abuse within the 12 months before screening or a positive result of
drug abuse test at screening;
11. Consumption of any nutrients known to modulate cytochrome P450 enzymes or P-gp
substrates activity (eg, grapefruit, pomelo, mango, star fruit, Seville [blood] orange
products, caffeine or xanthine-containing food or beverages) within 72 h before the
first dose of IMPs;
12. Clinically significant laboratory abnormalities, as determined by the Investigator,
including but not limited to (If the results are beyond the normal range or
significantly changed, the investigator deems it necessary to repeat the measurement,
vital signs and 12-Lead ECG may be repeated twice, clinical laboratory tests
[hematology, urinalysis, biochemistry and coagulation function test] may be repeated
once):
- Systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥
90 mmHg after 5 minutes of supine rest;
- Supine resting bradycardia (pulse heart rate [HR] <40 bpm) or a supine resting
tachycardia (HR >100 bpm);
- A corrected QT (QTc) interval of > 450 ms for males and > 470 ms for females
(Fridericia's method);
- Liver function: aspartate aminotransferase [AST], alanine transaminase [ALT],
alkaline phosphatase [ALP], γ-glutamyl transferase [γ- GGT]) or total bilirubin
(TBIL) >1.5 × upper limit of normal (ULN);
- Renal function: creatinine clearance rate ≤80 mL/min (calculated based on
Cockcroft-Gault formula);
- Other laboratory parameters demonstrating clinically significant abnormalities,
as determined by the investigator;
13. Known active infections, e.g., bacterial, fungal and viral infections, including:
- Human immunodeficiency virus (HIV) infection: defined as HIV antibody positive;
- Syphilis infection: defined as treponema pallidum antibody (TP-Ab) positive;
- Active hepatitis B virus (HBV): defined as hepatitis B surface antigen (HBsAg)
positive, Hepatitis B core antibody (HBcAb) positive and hepatitis B virus
(HBV)-deoxyribonucleic acid (DNA) ≥ lab-specific ULN (for those with positive
result on HBcAb or HBsAg, HBV DNA test will be performed and those with positive
HBV DNA results will be excluded);
- Active hepatitis C virus (HCV): defined as HCV antibody (HCV-Ab) positive and
HCV-ribonucleic acid (RNA) positive, if HCV-Ab positive and HCV RNA negative can
be considered as eligible at the discretion of the Investigator;
14. Has donated blood or plasma within 30 days prior to screening or had a loss of whole
blood of more than 500 mL within the 30 days prior to screening, or receipt of a blood
transfusion within one year prior to screening;
15. The subject has difficulty in swallowing oral medications;
16. Inability to be venipunctured and/or tolerate venous access; Any conditions which
would make the subject unsuitable for enrollment or could interfere with the subject's
participation in or completion of the study in the opinion of the investigator.