QG101-23-0 Capsules SAD and MAD Study in Healthy Subjects
Study Details
Study Description
Brief Summary
This study consists of two parts, Parts A and B. Part A includes a single ascending dose (SAD) study in healthy subjects. Part B includes a multiple ascending dose (MAD) study in healthy subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A Five ascending dose levels (Cohort A1、Cohort A2、Cohort A3、Cohort A4 and Cohort A5) of SAD QG101-23-0 capsules (n=6) or placebo (n=2) |
Drug: QG101-23-0 capsules
Single and Multiple Dose for oral
Drug: Placebo
Single and Multiple Dose for oral
|
| Experimental: Part B Three ascending dose levels (Cohort B1、Cohort B2、Cohort B3) of MAD QG101-23-0 capsules (n=6) or placebo (n=2) |
Drug: QG101-23-0 capsules
Single and Multiple Dose for oral
Drug: Placebo
Single and Multiple Dose for oral
|
Outcome Measures
Primary Outcome Measures
- The safety and tolerability of single-dose ascending of oral QG101-23-0 capsules in healthy subjects [Day1-8 (SAD)]
Safety will be assessed by the number, severity and type of adverse events, including changes in clinical laboratory evaluations (e.g., Hematology, urinalysis, blood biochemistry, coagulation), vital signs (blood pressure, pulse rate, tympanic thermometers temperature and respiratory rate), ECGs (e.g., QTc interval, QRS duration, PR interval) and physical examinations
- The safety and tolerability of multiple-dose ascending oral QG101-23-0 capsules in healthy subjects [Day1-15 (MAD)]
Safety will be assessed by the number, severity and type of adverse events, including changes in clinical laboratory evaluations (e.g., Hematology, urinalysis, blood biochemistry, coagulation), vital signs (blood pressure, pulse rate, tympanic thermometers temperature and respiratory rate), ECGs (e.g., QTc interval, QRS duration, PR interval) and physical examinations
Secondary Outcome Measures
- Maximum observed concentration（Cmax） [Day1-8 (SAD)]
Pharmacokinetics
- Time of Cmax（Tmax） [Day1-8 (SAD)]
Pharmacokinetics
- Area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration（AUC0-t） [Day1-8 (SAD)]
Pharmacokinetics
- AUC from time 0 to 12 hours（AUC0-12） [Day1-8 (SAD)]
Pharmacokinetics
- AUC from time 0 to 24 hours（AUC0-24） [Day1-8 (SAD)]
Pharmacokinetics
- AUC extrapolated from time 0 to infinity（AUC0-∞） [Day1-8 (SAD)]
Pharmacokinetics
- Apparent terminal elimination half-life （t1/2） [Day1-8 (SAD)]
Pharmacokinetics
- Apparent distribution volume corrected for bioavailability（Vd/F） [Day1-8 (SAD)]
Pharmacokinetics
- Apparent volume of distribution at steady-state (Vss) [Day1-8 (SAD)]
Pharmacokinetics
- Apparent terminal elimination rate constant (λz) [Day1-8 (SAD)]
Pharmacokinetics
- Mean residence time (MRT) [Day1-8 (SAD)]
Pharmacokinetics
- Apparent total clearance (CL) [Day1-8 (SAD)]
Pharmacokinetics
- Observed maximum concentration at steady state (Cmax,ss) [Day1-15 (MAD)]
Pharmacokinetics
- Observed minimum concentration at steady state (Cmin,ss) [Day1-15 (MAD)]
Pharmacokinetics
- Time of Cmax at steady state (Tmax,ss) [Day1-15 (MAD)]
Pharmacokinetics
- Average Concentration at steady state (Cav,ss) [Day1-15 (MAD)]
Pharmacokinetics
- Time of observed minimum concentration at steady state (Tmin,ss) [Day1-15 (MAD)]
Pharmacokinetics
- After steady state, the interval from 0 point of one administration to administration τ Area under the plasma concentration - time curve (AUC0-τ，ss) [Day1-15 (MAD)]
Pharmacokinetics
- After steady state, the area under the blood concentration - time curve from 0 point of one administration to infinity （AUC0-∞，ss） [Day1-15 (MAD)]
Pharmacokinetics
- Area under the concentration-time curve from time 0 to the end of the dosing interval (AUC0-tau) [Day1-15 (MAD)]
Pharmacokinetics
- Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) [Day1-15 (MAD)]
Pharmacokinetics
- Apparent terminal elimination half-life (t1/2) [Day1-15 (MAD)]
Pharmacokinetics
- CL for bioavailability at steady state (CL/F, ss) [Day1-15 (MAD)]
Pharmacokinetics
- Vd/F at steady state (Vd/F, ss) [Day1-15 (MAD)]
Pharmacokinetics
- Mean residence time (MRT) [Day1-15 (MAD)]
Pharmacokinetics
- Accumulation ratio (AR) [Day1-15 (MAD)]
Pharmacokinetics
- Accumulation ratios for Cmax [Day1-15 (MAD)]
Pharmacokinetics
- Accumulation ratios for AUC [Day1-15 (MAD)]
Pharmacokinetics
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males or females, between 18 and 55 years of age, inclusive.
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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).
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In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead 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.
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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.
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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.
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Females of non-childbearing potential defined as permanently sterile (i.e., due to hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy) or postmenopausal (defined as at least 12 months post cessation of menses without an alternative medical cause and follicle-stimulating hormone level ≥ 30 IU/L).as detailed in Appendix 2.
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Able to comprehend and willing to sign an Informed Consent Form (ICF) and to abide by the study restrictions.
Exclusion Criteria:
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Significant history or clinical manifestation of any metabolic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, acute or chronic infectious diseases and malignancies, as determined by the investigator (or designee).
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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 normalized ratio >1.5);
-
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;
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History of acute and chronic kidney disease including acute and chronic renal insufficiency. Or creatinine clearance < 60 mL/min at Screening or Check-in
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Abnormal blood pressure (defined as systolic blood pressure >140 mmHg or <90 mmHg, diastolic blood pressure >90 mmHg or <50 mmHg) at Screening or Check-in;
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History of 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).
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Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), and/or positive human immunodeficiency virus (HIV) test at Screening.
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Any of the following on the ECG.
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ECG is abnormal and clinically significant, or the corrected Corrected QT (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.
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QRS duration>120 msec, confirmed by repeat measurement at least two times.
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PR interval >220 msec, confirmed by by repeat measurement at least two times.
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Findings which would make QTc measurements difficult or QTc data uninterpretable.
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History of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome).
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Abnormal QRS or ST segment indicates a clinical significant abnormality of myocardia, e.g. cardiomyopathy, cardiac ischemia or myocardial infarction, etc.
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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 [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin]) that would potentially alter gastrointestinal peristalsis, potential of hydrogen (pH), absorption and/or excretion of orally administered drugs.
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Pregnant or lactating females or females of childbearing potential and males are unwilling to take effective contraceptive measures.
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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.
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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 dosing, unless deemed acceptable by the investigator (or designee).
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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.
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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 Corona Virus Disease 2019 (COVID-19) vaccines) or a biological product within 30 days (or within 5 half-lives of the test drug) prior to dosing.
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History of alcoholism, drug/chemical abuse or substance abuse within 6 months prior to Check-in. Alcoholism standard: alcohol consumption of > 21 units per week for males and > 14 units per week for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
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Positive alcohol breath test result or positive urine drug screen at Screening or Check-in.
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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.
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Smoke more than 5 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.
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Poor peripheral venous access.
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In addition to the above, subject who, in the opinion of the investigator (or designee), should not participate in this study.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amckaus PTY LTD.
- Novotech (Australia) Pty Limited
Investigators
- Principal Investigator: Angela Rowland, CMAX Clinical Research Pty Ltd
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Aom0315-ACT-01