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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05650528

Registration number

NCT05650528

Ethics application status

Date submitted

29/11/2022

Date registered

14/12/2022

Date last updated

1/08/2023

Titles & IDs

Public title

QG101-23-0 Capsules SAD and MAD Study in Healthy Subjects

Scientific title

Single-center, Randomised, Double-blind, Placebo-controlled Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile of Single- and Multiple-dose Ascending Oral QG101-23-0 Capsules in Healthy Subjects

Secondary ID [1]

Aom0315-ACT-01

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Healthy Volunteers

Condition category

Condition code

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - QG101-23-0 capsules
Treatment: Drugs - Placebo

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)

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)

Experimental: Part C - Cohort A3 Group 1 (n=8) and Group 2 (n=6) will participate in the food effect study. The subjects will take QG101-23-0 capsules while under fasting or fed condition.

Treatment: Drugs: QG101-23-0 capsules
Single and Multiple Dose for oral

Treatment: Drugs: Placebo
Single and Multiple Dose for oral

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

The safety and tolerability of single-dose ascending of oral QG101-23-0 capsules in healthy subjects

Timepoint [1]

Day1-8 (SAD)

Primary outcome [2]

The safety and tolerability of multiple-dose ascending oral QG101-23-0 capsules in healthy subjects

Timepoint [2]

Day1-15 (MAD)

Secondary outcome [1]

Maximum observed concentration(Cmax)

Timepoint [1]

Day1-8 (SAD)

Secondary outcome [2]

Time of Cmax(Tmax)

Timepoint [2]

Day1-8 (SAD)

Secondary outcome [3]

Area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration(AUC0-t)

Timepoint [3]

Day1-8 (SAD)

Secondary outcome [4]

AUC from time 0 to 12 hours(AUC0-12)

Timepoint [4]

Day1-8 (SAD)

Secondary outcome [5]

AUC from time 0 to 24 hours(AUC0-24)

Timepoint [5]

Day1-8 (SAD)

Secondary outcome [6]

AUC extrapolated from time 0 to infinity(AUC0-8)

Timepoint [6]

Day1-8 (SAD)

Secondary outcome [7]

Apparent terminal elimination half-life (t1/2)

Timepoint [7]

Day1-8 (SAD)

Secondary outcome [8]

Apparent distribution volume corrected for bioavailability(Vd/F)

Timepoint [8]

Day1-8 (SAD)

Secondary outcome [9]

Apparent volume of distribution at steady-state (Vss)

Timepoint [9]

Day1-8 (SAD)

Secondary outcome [10]

Apparent terminal elimination rate constant (?z)

Timepoint [10]

Day1-8 (SAD)

Secondary outcome [11]

Mean residence time (MRT)

Timepoint [11]

Day1-8 (SAD)

Secondary outcome [12]

Apparent total clearance (CL)

Timepoint [12]

Day1-8 (SAD)

Secondary outcome [13]

Observed maximum concentration at steady state (Cmax,ss)

Timepoint [13]

Day1-15 (MAD)

Secondary outcome [14]

Observed minimum concentration at steady state (Cmin,ss)

Timepoint [14]

Day1-15 (MAD)

Secondary outcome [15]

Time of Cmax at steady state (Tmax,ss)

Timepoint [15]

Day1-15 (MAD)

Secondary outcome [16]

Average Concentration at steady state (Cav,ss)

Timepoint [16]

Day1-15 (MAD)

Secondary outcome [17]

Time of observed minimum concentration at steady state (Tmin,ss)

Timepoint [17]

Day1-15 (MAD)

Secondary outcome [18]

After steady state, the interval from 0 point of one administration to administration t Area under the plasma concentration - time curve (AUC0-t,ss)

Timepoint [18]

Day1-15 (MAD)

Secondary outcome [19]

After steady state, the area under the blood concentration - time curve from 0 point of one administration to infinity (AUC0-8,ss)

Timepoint [19]

Day1-15 (MAD)

Secondary outcome [20]

Area under the concentration-time curve from time 0 to the end of the dosing interval (AUC0-tau)

Timepoint [20]

Day1-15 (MAD)

Secondary outcome [21]

Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf)

Timepoint [21]

Day1-15 (MAD)

Secondary outcome [22]

Apparent terminal elimination half-life (t1/2)

Timepoint [22]

Day1-15 (MAD)

Secondary outcome [23]

CL for bioavailability at steady state (CL/F, ss)

Timepoint [23]

Day1-15 (MAD)

Secondary outcome [24]

Vd/F at steady state (Vd/F, ss)

Timepoint [24]

Day1-15 (MAD)

Secondary outcome [25]

Mean residence time (MRT)

Timepoint [25]

Day1-15 (MAD)

Secondary outcome [26]

Accumulation ratio (AR)

Timepoint [26]

Day1-15 (MAD)

Secondary outcome [27]

Accumulation ratios for Cmax

Timepoint [27]

Day1-15 (MAD)

Secondary outcome [28]

Accumulation ratios for AUC

Timepoint [28]

Day1-15 (MAD)

Eligibility

Key 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.

Minimum age

18 Years

Maximum age

55 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key 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.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Other

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

20/02/2023

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

1/06/2024

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

CMAX Clinical Research Pty Ltd - Adelaide

Recruitment postcode(s) [1]

- Adelaide

Funding & Sponsors

Primary sponsor type

Commercial sector/Industry

Name

Amckaus PTY LTD.

Address

Country

Other collaborator category [1]

Commercial sector/Industry

Name [1]

Novotech (Australia) Pty Limited

Address [1]

Country [1]

Ethics approval

Ethics application status

Summary

Brief summary

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).

Trial website

https://clinicaltrials.gov/ct2/show/NCT05650528

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Angela Rowland

Address

CMAX Clinical Research Pty Ltd

Country

Phone

Fax

Contact person for public queries

Name

Huaqin Shi

Address

Country

Phone

+86-571-86504023

Fax

shihuaqin@adamerck.com

Contact person for scientific queries

Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05650528

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05650528