Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000725965
Ethics application status
Approved
Date submitted
1/06/2020
Date registered
7/07/2020
Date last updated
7/07/2020
Date data sharing statement initially provided
7/07/2020
Date results information initially provided
7/07/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
A randomized, double-blind, placebo-controlled dose-escalation study of AND017 capsules in healthy subjects following oral single and multiple dose administration
Scientific title
A randomized, double-blind, placebo-controlled dose-escalation study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of AND017 following oral single and multiple dose administration
Secondary ID [1] 301388 0
BB-AND017AU001
Universal Trial Number (UTN)
U1111-1252-6698
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaemia 317692 0
Condition category
Condition code
Blood 315768 315768 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a phase I, randomized, double-blind, placebo-controlled, dose-escalation study to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AND017 in healthy subjects. The study will involve two sequential parts: a single ascending dose (SAD) phase (Part A) followed by a multiple ascending dose (MAD) phase (Part B).

In the SAD doses of 1, 4, 10, 20, 30, and 50 mg AND017 (n=6/dose) or placebo (n=2/dose) will be assessed in six consecutive cohorts of 8 subjects except Cohort 1 (6 subjects randomized at 4:2 to receive AND017 or placebo). In the MAD doses of 4, 10, 20, and 30 mg AND017 (n=6/dose) or placebo (n=2/dose) will be administered daily for 10 days and assessed in four consecutive cohorts of 8 subjects. Subjects will be fasted for at least 10 hours before oral administrating the investigational product AND017 or placebo capsules with 240 mL water on dosing days. Subjects in the SAD will be inpatients for approximately 4 days with study drug administered on Day 1, and subjects in the MAD will be inpatients for approximately 14 days with study drug administered on Days 1-10. Subjects will be enrolled only in one study part and randomized to one cohort per the randomization schedule.

SAD. Healthy subjects will be screened within 21 days prior to dosing. Subjects will be admitted to the clinical facility on Day -1 for up to 4 days. Oral administration of a single dose of AND017 or placebo capsules will occur on Day 1. Following completion of all safety assessments and sampling for PK analyses, subjects will be discharged on Day 4.
Double-blind dosing will occur in cohorts 1 through 6. In all cohorts except cohort 1, 6 participants will receive oral administrating AND017 capsules and 2 participants will receive matching placebo. Doses will escalate in the dose range of 1 mg to 50 mg. The dose escalation steps may be altered following review of the safety data upon completion of each cohort.
In Cohort 1, (4 AND017, 2 placebo) 2 participants (sentinels) will be dosed at least 24 hours prior to the remaining participants. One sentinel will be orally dosed with AND017 and the other with matching placebo. The remaining 4 participants will only be dosed if no safety are identified in the sentinel participants. The non-sentinel participants in Cohort 1 will be admitted to the clinical research facility at least 24 hours later than the sentinels. There will be no sentinels in Cohorts 2-6.
In the SAD part of the study, all participants will be admitted to the clinical research unit on Day 1. Oral dosing will take place on the morning of Day 1.
After each SAD dose cohort has completed oral administration of study drug and evaluation, the Safety Review Committee (SRC) will review blinded cumulative safety data (including the follow-up visit data) to determine the safety and tolerability of study drug. If the dose level is determined to be safe and tolerated, the next dose cohort will be enrolled and randomized to receive the next dose level of active AND017 or placebo.
The SRC will review the data, discuss the findings, and decide to: 1) enroll the next dose cohort at the protocol-defined dose level; 2) enroll the next dose cohort at an intermediate dose level; or 3) terminate enrollment in the SAD part of the study. If the dose level is determined not to be safe and tolerated, the study drug assignment for those participants with a safety concern may be un-blinded.

MAD. The MAD part of the study will commence following the establishment of safety and tolerability of Cohort 6 in the SAD. The SRC will evaluate the safety and tolerability data obtained for the participants in Cohorts 1-6 to determine if appropriate the dose levels planned to be utilized in the MAD cohorts (Cohort 7-10). 4 dose levels are anticipated to be evaluated in the MAD. Up to 2 additional cohorts may be added for the purposes of cohort expansion or to explore a dose level intermediate to previously evaluated doses.
In the MAD part of the study, all subjects will be screened within 21 days prior to dosing and will be admitted to the clinical facility on Day 1. Oral dosing will commence on the morning of Day 1. Daily oral dosing will continue for 10 consecutive days. The last dose will be administered on the morning of Day 10. Subjects will be discharged on Day 17 following completion of all PK sample collection and safety assessments.
After each MAD dose cohort has completed oral administration of study drug and evaluation, the SRC will review blinded cumulative safety data (including the follow-up visit data) to determine the safety and tolerability of study drug. If the dose level is determined to be safe and tolerated, the next dose cohort will be enrolled and randomized to receive the next dose level of active AND017 or placebo.
The SRC will review the data, discuss the findings, and decide to: 1) enroll the next dose cohort at the protocol-defined dose level; 2) enroll the next dose cohort at an intermediate dose level; or 3) terminate enrollment in the MAD part of the study. If the dose level is determined not to be safe and tolerated, the study drug assignment for those participants with a safety concern may be un-blinded.
After the final MAD cohort has been completed, the Sponsor may, after consulting with the SRC, initiate up to two optional cohorts for the following purposes: to expand a previous dose level cohort; to explore a dose level that is intermediate between two doses that have already been evaluated as part of the MAD, or if the final dose level is determined to be safe and tolerated, explore a higher dose level. Dose levels anticipated to be evaluated in the MAD will be in the range of 4 –30 mg.
Intervention code [1] 317723 0
Treatment: Drugs
Comparator / control treatment
Size and weight-matching placebo (capsules) will be used by oral administration
Control group
Placebo

Outcomes
Primary outcome [1] 323975 0
To evaluate the safety and tolerability of AND017 following single and multiple dose oral administration in healthy adult subjects.
Timepoint [1] 323975 0
The safety and tolerability of AND017 will be assessed from screening until the end of study or early termination visit (if applicable).

Safety Evaluation:
1) Adverse Event;
2) Clinical laboratory tests (CBC, serum biochemistry, urinalysis,
coagulation);
3) Physical examination including cardiovascular, respiratory,
gastrointestinal and neurological systems;
4) 12-lead safety ECG (HR, PR, QRS, QT, QTc interval);
5) Vital signs (blood pressure (BP), heart rate (HR), respiration rate
(RR), and temperature).

Part A (SAD cohort evaluation):
1) Physical examination will be conducted on screening, Day 1 (check-in) and D7 (follow-up)
2) Alcohol breath test will be conducted on screening and Day 1 (check-in)
3) Pregnancy test will be conducted on screening, Day1 (check-in) and Day 4 (Exit).
4) Virology screening will be conducted on screening.
5) Blood samples will be collected for clinical laboratory test on screening, Day 1, Day 2, Day 4 (Exit) and Day 7 (follow-up)
6) 12-lead ECG will be done on screening, Day 1 (check-in and dosing period), Day 2, Day 3, Day 4 (Exit) and Day 7 (follow-up).
7) Vital signs will be measured on screening, Day 1 (check-in and dosing period), Day 2, 3, 4 (Exit), and 7 (follow-up).

AE monitoring and concomitant medications monitoring will be performed the entire period from screening to follow-up.

Part B (MAD cohort evaluation):
1) Physical examination will be conducted on screening, Day 1 (check-in) and D17 (follow-up)
2) Alcohol breath test and drugs of abuse screen will be conducted on screening and Day 1 (check-in)
3) Pregnancy test will be conducted on screening, Day1 (check-in) and Day 15 (Exit).
4) Virology screening will be conducted on screening.
5) Blood samples will be collected for clinical laboratory test on screening, Day 1 (check-in), Day 2, Day 4, Day 6, Day 8, Day10, Day 15 (Exit) and Day 17 (follow-up)
6) 12-lead ECG will be done on screening, Day 1 (check-in and dosing period), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 (Exit) and Day 17 (follow-up).
7) Vital signs will be measured on screening, Day 1 (check-in and dosing period), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 (Exit) and Day 17 (follow-up).

AE monitoring and concomitant medications monitoring will be performed the entire period from screening to follow-up.
Secondary outcome [1] 383473 0
To characterize the pharmacokinetics properties of AND017 in plasma following single and multiple oral dose administration.
Timepoint [1] 383473 0
The parameters by which the pharmacokinetics (PK) of AND017 will be measured are as below:
SAD cohort evaluation (Part A) (Cohorts 1-6): Blood samples will be obtained on dosing Day at time 0 (within 1h pre-dose), 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 10 h, 12 h, 24 h, 48 h, 72 h post dose.

MAD cohort evaluation (Part B) (Cohorts 1-4): Blood samples will be collected on the 1st dosing Day at time 0 (within 1 h pre-dose), 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 10 h, 12 h, 24 h post dose; within 1 h pre-dose on the 6th, 7th, 8th dosing Day (for steady state assessment); on the 10th dosing Day at time 0 (within 1 h pre-dose), 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 10 h, 12 h, 24 h, 48 h and 72 h post dose.

SAD cohort evaluation (Part A:single dose cohort): PK parameters including but not limit to
1) Maximum (peak) plasma concentration (Cmax),
2) Time to reach maximum(peak) plasma concentration following drug administration (Tmax),
3) Elimination half-life (t1/2),
4) Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t),
5) Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf),
6) Apparent total body clearance of the drug from plasma (CL/F),
7) Apparent volume of distribution (Vz/F),
8) Mean residence time (MRT),
9) Terminal disposition rate constant
10) Percentage of AUC(0-infinity) obtained by extrapolation (%AUCex)

MAD cohort evaluation (Part B: Multiple dose cohort): PK parameters including but not limit to:
1) Minimum steady-state plasma concentration during a dosage interval (Css,min)
2) Maximum(peak) steady-state plasma concentration during a dosage interval (Css,max),
3) Average steady-state plasma drug concentration during multiple-dose administration (Css,avg),
4) Elimination half-life (t1/2),
5) Time to reach Css. Max (Tss,max),
6) Area under the plasma concentration-time curve during a dosage interval(t) (AUC0-t),
7) Apparent total body clearance after oral administration at steady state (CLss/F),
8) Apparent volume of distribution at steady-state after oral administration (Vss/F),
9) Terminal disposition rate constant
10) Accumulation ratio calculated from AUCt,ss adn AUCt (Rac (AUC)),
11) Accumulation ratio calculated from Cmax,ss and Cmax (Rac (Cmax))
12) Dose bioavailability (DF)
Secondary outcome [2] 383474 0
Preliminarily evaluate the pharmacodynamics response of AND017 following single and multiple oral dose administration.
Timepoint [2] 383474 0
The parameters by which the pharmacodynamics (PD) of AND017 will be measured as below:

SAD cohort evaluation (Part A): EPO and absolute reticulocyte count: actual values, maximum change and maximum percent change from baseline and time to achieve the maximum, percent of change from baseline;
MAD cohort evaluation (Part B): EPO, Hemoglobin, absolute reticulocyte count and total RBCs: actual values, maximum change and maximum percent change from baseline and time to achieve the maximum, percent of change from baseline.

SAD cohort evaluation (Part A: Cohorts 1-6):
1) EPO: Blood samples will be collected on Day-1, dosing Day at time 0 (within 1 h pre-dose) and at 4 h, 6 h, 10 h, 12 h and 24 h post dose;
2) Absolute reticulocyte count: Blood samples will be collected on Day1, dosing Day at time 0 (within 1 h pre-dose) and at, 24 h, 48 h, 72 h post dose and on Day of Follow-up.

MAD cohort evaluation (Part B: Cohorts 1-4):
1) EPO: Blood samples will be collected on Day -1, the 1st and the 10th dosing Day at time 0 (within 1h pre-dose) and at 4 h, 6 h, 10 h, 12 h and 24 h post dose;
2) Hemoglobin, RBC, absolute reticulocyte count: Blood samples will be collected on Day -1, at time 0(within 1h pre-dose) on the 1st, 2nd, 4th, 6th, 8th, 10th dosing Days, 24h after the last dose, and Days of Exit and Follow-up.

Test methods:
1. EPO: Blood was collected to the 5ml Gold-top SST tube. The tube is filled to capacity. Invert the tube 5-10 times after filling. Do not shake. Centrifuge the tube at 1300g for 10 min after the clot is fully formed. Transfer serum into a 5ml aliquot tube. The level of EPO in serum was measured by EPO ELISA assay.
2. Hemoglobin, RBC, and absolute reticulocyte count: Blood was collected to a 4ml Lavender-top blood collection tube (EDTA), invert the tube 5-10 times after filling to capacity. Sent sample in primary tube to a pathology lab for testing as part of routine haematology test.

Eligibility
Key inclusion criteria
Each subject must meet the following criteria to be enrolled in this
study:
1. Healthy male or female, 18-45 years of age (both inclusive);
2. Able to give signed written informed consent form;
3. Able to remain in house for the duration of the study without interruption;
4. Body mass index (BMI, weight [kg]/height2 [m]2) within 18.0-30.0 kg/m2 (both inclusive);
5. Blood Pressure (BP) and 12-lead electrocardiogram (ECG) showing
no clinically significant abnormalities during screening;
6. Subjects have no clinically significant abnormal values on physical examination, clinical laboratory test, liver function or kidney function;
7. Agree to completely refrain from consuming alcohol, caffeinated beverages (i.e. tea, coffee, etc.), and tobacco from 24 h pre the 1st dose until the last PK blood sample collection is finished;
8. If male, a willingness not to donate sperm and if engaging in sexual intercourse with a female partner who could become pregnant, a willingness to use a condom in addition to having the female partner use a highly effective method of birth control (such as an intrauterine device, diaphragm, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation). This criterion applies to males (and/or female partners) who are surgically sterile and must be followed from the time of first study drug administration until 90 days after the final administration of study drug.
9. If female, be of non-childbearing potential (e.g. post-menopausal as demonstrated by follicle stimulating hormone (FSH) or surgical sterilization i.e., tubal ligation or hysterectomy). Provision of documentation is not required for female sterilization, verbal confirmation is adequate; If of childbearing potential females must use a highly effective method of birth control (such as an intrauterine device, diaphragm, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation).
10. Negative urine drug screen at screening and Day-1.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects who meet any of the following criteria will be excluded from
the study:
1. History of severe drug (e.g. or asthma induced by aspirin) or excipient allergy, or hypersensitivity to AND017 capsules or other HIF-PHD inhibitors;
2. Current or chronic history of liver disease or known hepatic or biliary abnormalities (except Gilbert’s syndrome or asymptomatic gallstones), including but not limited to ALT, alkaline phosphatase and bilirubin greater than 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin greater than 35%);
3. Subjects with Hb: male (less than 120 g/L or greater than 160 g/L), female (less than 110 g/L or greater than 150 g/L);
4. Subjects with any abnormalities of hematology during screening: Mean corpuscular volume (MCV), platelet count, serum iron, ferritin;
5. Subjects with the history of medicine or disease to increase the risk of bleeding or disturbance of blood coagulation;
6. History of deep vein thrombosis, stoke, transient ischemic attack, pulmonary embolism or other thrombosis related condition within the last five years;
7. History of myocardial infarction, heart failure or acute coronary syndrome;
8. History of pulmonary artery hypertension;
9. Evidence of active peptic, duodenal or esophageal ulcer disease at screening;
10. Subjects with major illness or surgery (except for minor outpatient surgery) within past 3 months prior to screening, or planned surgery during study;
11. History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency);
12. Subjects with intolerance to direct venipuncture;
13. Known or suspected history of drug abuse within the past 5 years or presence of drug abuse within 3 months before study;
14. Participation in any clinical study with an investigational drug, biologic or device within 4 weeks or 5 times the half-life of the specific drug/biologics (whichever is longer), prior to dosing;
15. Donated blood greater than 400 mL or significant blood loss equivalent to 400 mL or received blood transfusion within 3months of screening; or donated blood greater than 200 mL or significant blood loss equivalent to 200 mL within 1 month prior to screening
16. Use of any other drug, including over-the-counter medications, herbs, within 14 days prior to the first dose of study medication (except for contraceptive medication in WOCBP);
17. Take in food or drink beverages which can influence metabolism of liver 7 days prior to the first dose of the study drug (e.g. grapefruit & Seville oranges );
18. Habitual use of nicotine products or smoking within 3 months (more than 5 cigarettes per day) prior to screening;
19. History of significant alcohol abuse within 6 months of screening or any indication of regular use of more than 14 units of alcohol per week (1 Unit equal to 360 mL of beer or 45 mL of alcohol 40% or 150 mL of wine) or taking the product containing alcohol 2 days prior to dosing;
20. Positive screening test for any one or more: serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, or HIV;
21. Malignancy within 5 years within screening visit (except basal cell skin carcinoma);
22. Subject who is considered unsuitable for participating in the study in the opinion of investigator;
23. Nursing mothers, pregnancy women

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)
The randomization code will be generated by a CRO statistician not directly involved with the study. The un-blinded CRO statistician will provide the randomization code lists to the un-blinded pharmacist. The pharmacist will dispense the appropriate number of 1/4/10mg AND017 or matching placebo capsules for each study subject into labelled HDPE bottles based on the Randomization Schedule. The capsules can be dispensed into HDPE bottles up to 7 days before dosing by pharmacist. The site number is 2 digital, the screening number is 3 digital, the site number + the screening number-the subject number.
Randomization number will be composed of one letter and four digital numbers. The first letter is S or M, means the part of the study. The second number is the cohort, the third number indicates if the subject enrols as a replacement, the other two digital number is the subject sequence number.

All other personnel directly related to this study (i.e., Investigators, site personnel, monitors, CRO personnel, Sponsor personnel) will remain blinded until completion of the study, at which time the randomization code will be broken. The CRO will obtain written consent from the Sponsor prior to breaking the code.

For each participant, an individual sealed envelope containing the randomization code will be kept at Scientia. This randomization information may be opened and the randomization for any particular subject may be made available to the PI only in the event of a medical emergency or an AE that necessitates identification of the study drug for the welfare of that subject. In the event of a medical emergency, it is requested that the investigator make every effort to contact the Sponsor or Sponsor’s monitor prior to breaking the code. Whenever possible, the investigator or sub investigator should consult with the sponsor prior to breaking the blind.

Breaking of the randomization code is to be performed only with Sponsor approval except in the event of a medical emergency where the code may be broken immediately. If it becomes necessary to break the code during the study, the sponsor should be informed and the date, time and reason will be recorded in the participant's Source document and on the individual envelope. A written report should be sent to the Sponsor within 1 working day.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The 6 subjects in the Part A Cohort 1 will be randomized at 2:1 ratio to receive AND017 or placebo. The 8 Subjects in the rest of Part A (Cohorts 2-6 and Part B Cohorts 1-4 will be randomized at 3:1 ratio to receive AND017 or placebo. Subjects will be enrolled only in one study part and randomized to one cohort per the randomization schedule.
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
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
General analysis
WinNonlin v6.4/SAS® 9.3 or higher version will be used for statistical analysis. Generally continuous measurements are summarized by means of descriptive statistics (i.e. number of observations [N], arithmetic mean [Mean], standard deviation [SD], coefficient of variation [CV], Geometric mean (Geometric Mean) and Geometric coefficient of variation [Geometric CV], median, minimum [Min], and maximum [Max]) and categorical data are summarized by means of frequency tables (i.e.
counts [N] and percentages).

Safety analysis
Safety of the study drug will be assessed by collection and review of adverse events, laboratory parameters, physical examination, vital signs and ECG parameters throughout the duration of the study.
Safety analysis will involve examination of the descriptive statistics and individual particle listings for any effects of study treatment on safety. Incidence of treatment emergent AEs will be summarized by Cohort.

PK analysis
PK parameters of AND017 (e.g. Cmax, AUC0-t, AUC0-inf, Tmax, t1/2, Vz/F, CL/F) will be analyzed by non-compartmental analysis (NCA) with WinNonlin Version 6.4 or above. The AND017 PK parameters as mentioned above will be listed by individual subject, summarized by dosage, single and multiple doses treatment.

PD analysis
EPO, absolute reticulocyte count, Hb, RBCs at specified time points will be listed for each subject and summarized by dose level. Results from placebo subjects will be pooled across Cohorts.
Actual values of hemoglobin and percent change from baseline at specified time points will be listed for each subject and will be summarized by dose level. Results from placebo subjects will be pooled across Cohorts.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
15/01/2019
Date of last participant enrolment
Anticipated
Actual
2/08/2019
Date of last data collection
Anticipated
Actual
19/08/2019
Sample size
Target
78
Accrual to date
Final
78
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 16785 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 30408 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 305830 0
Commercial sector/Industry
Name [1] 305830 0
BalanceBio Pty Ltd
Country [1] 305830 0
Australia
Funding source category [2] 305852 0
Commercial sector/Industry
Name [2] 305852 0
Kind Pharmaceutical Co. Ltd
Country [2] 305852 0
China
Primary sponsor type
Commercial sector/Industry
Name
BalanceBio Pty Ltd
Address
Suite 201, 370 Pitt St. Sydney, NSW2000, Australia
Country
Australia
Secondary sponsor category [1] 306274 0
Commercial sector/Industry
Name [1] 306274 0
Kind Pharmaceutical Co. Ltd
Address [1] 306274 0
Floor 17, Building 4, Health Valley, #1500 West Wenyi Road, Hangzhou, Zhejiang province, 311122, China
Country [1] 306274 0
China

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306096 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 306096 0
123 Glen Osmond Road Eastwood Adelaide
South Australia 5063
Ethics committee country [1] 306096 0
Australia
Date submitted for ethics approval [1] 306096 0
10/10/2018
Approval date [1] 306096 0
05/12/2018
Ethics approval number [1] 306096 0
2018-10-840-A-1

Summary
Brief summary
This is a phase I, randomized, double-blind, placebo-controlled, dose-escalation study to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD)of AND017 in healthy subjects. The
study will involve two sequential parts: a single dose phase (SAD cohorts, Part A) followed by a multiple dose phase (MAD cohorts, Part B). Single doses of 1, 4, 10, 20, 30, and 50 mg AND017(n=6/dose) or placebo (n=2/dose) will be
assessed in six consecutive cohorts of 8 subjects each in SAD cohorts (Part A) except Cohort 1 (4 subjects randomized at 1:1 to receive AND017 or placebo). Multiple doses of 4, 10, 20, and 30 mg AND017 (n=6/dose) or placebo (n=2/dose) will be administered daily for 10 days and assessed in four consecutive cohorts of 8 subjects each in MAD cohorts (Part B). Subjects will be fasted for at least 10 hours before administrating the investigational medicine with 240 mL water on dosing days. Subjects in SAD cohorts (Part A) will be inpatient for approximately 4 days with study drug administered on Day 1, and subjects in MAD cohorts (Part B) will be inpatient for approximately 14 days with study drug administered on Days 1-10. Subjects will be enrolled only in one study part and randomized to one cohort per the randomization schedule.
For safety purpose, a sentinel dosing design will be applied in Cohort 1 (SAD cohort, Part A). The first 2 subjects will be dosed with one subject receiving AND017 and the other receiving placebo. After an interval of 48 h and
review of all safety data of sentinel subjects, the remaining 4 subjects will be randomized at 3:1 to receive AND017 or placebo. There will be also a safety review (4 and 10 days in SAD (Part A) and MAD cohorts (Part B), respectively) before
dose escalation for each cohort. Dose escalation will be stopped when predefined safety or pharmacodynamic criteria are met. This study allows some alteration from the currently outlined dosing schedule to reduce risk of subjects. Additional dosing cohorts may also be added to further evaluate the safety, PK and/or PD of AND017.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102690 0
Dr James Kuo
Address 102690 0
Scientia Clinical Research Ltd, Bright Building, Levels 5 & 6, Corner High & Avoca Street, Randwick, NSW 2031, Australia
Country 102690 0
Australia
Phone 102690 0
+61 2 93825800
Fax 102690 0
Email 102690 0
[email protected]
Contact person for public queries
Name 102691 0
Dr James Kuo
Address 102691 0
Scientia Clinical Research Ltd, Bright Building, Levels 5 & 6, Corner High & Avoca Street, Randwick, NSW 2031, Australia
Country 102691 0
Australia
Phone 102691 0
+61 2 93825800
Fax 102691 0
Email 102691 0
[email protected]
Contact person for scientific queries
Name 102692 0
Dr James Kuo
Address 102692 0
Scientia Clinical Research Ltd, Bright Building, Levels 5 & 6, Corner High & Avoca Street, Randwick, NSW 2031, Australia
Country 102692 0
Australia
Phone 102692 0
+61 2 93825800
Fax 102692 0
Email 102692 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The sponsor want to keep the IPD confidential at this stage.


What supporting documents are/will be available?

No Supporting Document Provided



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