Overview
The study will consist of three parts: a single-dose ascending (SAD) phase (Part A) enrolling a total of five ~ six cohorts of healthy participants, a multiple-dose ascending (MAD) phase (Part B) enrolling 3 cohorts of healthy participants, and a food effect study (Part C).
Description
This study is a single-center, randomized, double-blind and placebo-controlled trial. Healthy subjects will receive single- and multiple-dose administration through oral of different doses of QG101-23-0 capsules to evaluate its safety, tolerability and pharmacokinetics profile.
Eligibility
Inclusion Criteria：
Subjects must satisfy all the following criteria at the Screening visit and Check-in unless
otherwise stated:
1. Males or females, between 18 and 55 years of age, inclusive.
2. Body weight is ≥ 50.0 kg for male subjects and ≥ 45.0 kg for female subjects, with a
body mass index (BMI) of 18-32 kg / m2 (inclusive).
3. In good health, determined by no clinically significant findings from medical history,
physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and
clinical laboratory evaluations at Screening and Check-in as assessed by the
Investigator (or designee), as applicable. Resting heart rate ≥ 45 bpm and ≤ 100 bpm
at Screening.
4. Male subjects must agree to refrain from sperm donation from the time of signing the
informed consent form until 90 days after the last dosing and females should refrain
from ova donation from the time of signing the informed consent form until 30 days
after the last dosing. As detailed in Appendix 2.
5. Females will not be pregnant or lactating, female subjects with a negative blood
pregnancy test during the Screening period and a negative urine pregnancy test at
Check-in, and male and female of childbearing potential having taken effective
contraceptive measures at least from the date of signing the informed consent form and
should agree to continue to use effective contraceptive measures from the date of
signing the informed consent form until 90 days after the last dosing for males and 30
days after the last dosing for females. Males with vasectomy at least 90 days prior to
the Screening visit must have documentation confirming Azoospermia or use other
contraceptives. As detailed in Appendix 2.
6. Females of nonchildbearing potential defined as permanently sterile (i.e., due to
hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy; at least 3
months between sterlization date and screening date) or postmenopausal (defined as at
least 12 months post cessation of menses without an alternative medical cause and
follicle-stimulating hormone [FSH] level ≥ 30 IU/L). As detailed in Appendix 2.
7. Able to comprehend and willing to sign an informed consent form (ICF) and to abide by
the study restrictions.
Exclusion Criteria：
Subjects will be excluded from the study if they satisfy any of the following criteria at
the Screening visit and Check-in unless otherwise stated:
1. Significant history or clinical manifestation of any metabolic, dermatological,
hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal,
neurological, respiratory, endocrine, or psychiatric disorder, acute or chronic
infectious diseases and malignancies, as determined by the Investigator (or designee).
2. History of hereditary bleeding disorders, coagulation disorders, non-traumatic
bleeding requiring treatment, or thromboembolism; or currently have any disease that
can cause bleeding (including coagulation disorder, thrombocytopenia [platelet count <
150×109/L] and prothrombin time-international normalised ratio > 1.5);
3. Acute and chronic liver disease or serum aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) ≥ 1.5 × the upper limit of normal at Screening or Check-in;
4. History of acute and chronic kidney disease including acute and chronic renal
insufficiency. Or impaired renal function defined by creatinine clearance (calculated
using the Cockcroft-Gault equation) < 90 mL/min at Screening or Check-in; See Appendix
3 Formulas Used in the Study.
5. Abnormal blood pressure (defined as systolic blood pressure > 145 mmHg or < 90 mmHg,
diastolic blood pressure > 90 mmHg or < 50 mmHg) at Screening or Check-in;
6. History of clinically significant hypersensitivity, any intolerance, or any
anaphylaxis to any drug compound including any components of the study drug capsules,
such as lactose, hydroxypropyl methylcellulose, magnesium stearate, food, or other
substance, unless approved by the Investigator (or designee).
7. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab),
and/or positive human immunodeficiency virus (HIV) test at Screening. Participants
with previously treated HCV and hence HCV Ab positive may be included if a subsequent
HCV RNA test is negative.
8. Any of the following on the ECG at Screening and Check-in (Day -1).
1. ECG is abnormal and clinically significant, or the corrected QTc interval (QTc is
calculated by Fridericia correction formula: QTc = QT/ [RR ^ 0.33]) > 450 msec
(male) or > 470 msec (female) is confirmed by repeat measurement at least two
times. See Appendix 3 Formulas Used in the Study.
2. QRS duration > 120 msec, confirmed by repeat measurement at least two times.
3. PR interval > 220 msec, confirmed by repeat measurement at least two times.
4. Findings which would make QTc measurements difficult or QTc data uninterpretable.
5. History of additional risk factors for torsades de pointes (e.g., heart failure,
hypokalaemia, family history of long QT syndrome).
6. Abnormal QRS or ST segment indicates a clinically significant abnormality of
myocardia, e.g., cardiomyopathy, cardiac ischaemia or myocardial infarction, etc.
9. History of stomach or intestinal surgery or resection, vagotomy, or any surgery
(uncomplicated appendectomy and hernia repair will be allowed, but not
cholecystectomy) or adverse syndromes (such as Crohn's disease, Irritable Bowel
Syndrome , chronic pancreatitis or congenital nonhaemolytic hyperbilirubinemia [e.g.,
suspicion of Gilbert's syndrome based on total and direct bilirubin, the subjects with
total or direct or indirect bilirubin > 35%× the upper limit of normal at Screening or
Check-in]) that would potentially alter gastrointestinal peristalsis, pH, absorption
and/or excretion of orally administered drugs.
10. Pregnant or lactating females or females of childbearing potential and males are
unwilling to take effective contraceptive measures.
11. Having foods and beverages containing poppy seeds, grapefruit and orange including
Seville oranges or wine containing extracts from the above fruits within 3 days prior
to Check-in until the follow-up visit.
12. Use or intend to use any medications / products including any prescription or
over-the-counter drugs known to alter drug absorption, metabolism, or elimination
processes, including vitamin therapy, minerals, and phytotherapeutic / traditional
Chinese medicine such as St. John's wort /plant-derived preparations, within 30 days
prior to the first dose of study medication until completion of the follow-up visit,
unless deemed acceptable by the Investigator (or designee).
13. Having lost blood or donated blood 500 mL or more, within 56 days prior to Screening.
Receipt of blood products within 60 days prior to Check-in. The Participants who plan
to donate blood from the Screening to 56 days after the follow-up visit.
14. Participation in a clinical study involving administration of an investigational drug
or having received any vaccines (including any new investigational vaccines and any
approved vaccines such as influenza or COVID-19 vaccines) or a biological product
within 30 days (or within five half-lives of the test drug) prior to dosing.
15. History of drug/chemical abuse or substance abuse; Regular consumption of the amount
of alcohol (in an Australian standard drink) of more than two standard drinks per day
or 14 standard drinks per week within 6 months prior to your admission to the clinical
unit (One standard drink is equivalent to 10 grams of alcohol: approximately 285 mL
full-strength beer or cider [4.9%], 375 mL mid-strength beer [3.5%], 425 mL light-
strength beer [2.7%], 100 mL wine or 30 mL shot of 40% spirit). A positive alcohol
breath test at Screening or Day -1, or inability to abstain from alcohol during the
study (Within 3 days prior to Check-in until the follow-up visit); Urine drugs of
abuse testing as detailed in Appendix 4.
16. Positive alcohol breath test result or positive urine drug screen at Screening or
Check-in. Urine drugs of abuse testing as detailed in Appendix 4.
17. History of febrile illness within 7 days prior to the first dose of study drug or
subjects with evidence of active infection at Check-in.
18. Smoke more than five cigarettes per day within 30 days prior to dosing (Day 1) or
inability to abstain from tobacco- or nicotine-containing products during the study
(Within 3 days prior to Check-in until the check-out) or positive at Screening or
Check-in for any other reason.
19. Poor peripheral venous access.
20. History of constipation or the inability to maintain regular bowel movements for the
subjects of Cohort A3 within 3 months before administration.
21. In addition to the above, subject who, in the opinion of the Investigator (or
designee), should not participate in this study.