Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001121651
Ethics application status
Approved
Date submitted
14/09/2023
Date registered
27/10/2023
Date last updated
31/05/2024
Date data sharing statement initially provided
27/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the Safety, Tolerability, Pharmacokinetics
and Food-Effect of MRX-5 Tablets in Healthy Adult Subjects
Scientific title
A Phase 1, Randomized, First-in-human Study to
Evaluate the Safety, Tolerability and Pharmacokinetics
of Single and Multiple Ascending Doses and Food-Effect
of MRX-5 Tablets in Healthy Adult Subjects
Secondary ID [1] 310507 0
MRX5-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infectious Bacterial disease 331308 0
Non-Tuberculous Mycobacterium 331561 0
Condition category
Condition code
Infection 328066 328066 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
MRX-5 is a novel synthetic antibiotic.

Investigational Product: MRX-5 Tablets or Matching Placebo

This study will be conducted in healthy adult subjects in 2 parts.

Part A- Single Ascending Dose (SAD) and Food-effect (FE): Cohort 1-6 (SAD) to receive placebo or MRX-5 as mentioned below.
Cohort 1: 50mg
Cohort 2: 100mg
Cohort 3: 200mg
Cohort 4: 400mg
Cohort 5: 800mg
Cohort 6: 1200mg

Cohort 7 (FE) is open label to receive a planned dose of 200mg on Day 1 under fasted condition and second dose on Day 8 (+3 days) in fed condition. In the fed state, a standard high-fat meal (total 800-1000 calories, 50 percent of calories derived from fat) is provided 30 minutes before dosing and consists of 150, 250 and 500-600 calories from Protein, Carbohydrates, Fat, respectively.

Part B- Multiple Ascending Dose (MAD): MAD Cohorts 1-3 to receive placebo or one of the following doses 200, 400 and 600mg daily for 10 days.

Subjects will be confined in a Clinical Research Unit during the dosing periods and will be monitored to ensure compliance with dosing.
Intervention code [1] 326943 0
Treatment: Drugs
Comparator / control treatment
The composition of the placebo is microcrystalline cellulose tablet
There is no comparator group for the food effect cohort.
Control group
Placebo

Outcomes
Primary outcome [1] 335997 0
To evaluate the safety and tolerability of single oral doses of MRX-5 Tablets in healthy adult subjects.

- Incidence and severity of treatment-emergent adverse events (TEAEs) will be assessed for severity and causality (relationship of event to the investigational product) by the study investigator using the specified definitions.
Common Terminology Criteria for Adverse Events (CTCAE) (V5.0) as 5 grades.
- Changes in clinical laboratory parameters including blood tests for complete blood count, coagulation, serum chemistry, and urinalysis.
- Change in vital signs measurements. Vital signs include measurement of heart rate (HR) respiration rate (RR), systolic and diastolic blood pressure (BP) and body temperature.
BP and HR will be measured by an automated BP Machine, RR is a manual calculation where the staff member will count the rise/fall of the chest and temperature will be measured by a digital tympanic thermometer
- Changes in the electrocardiogram (ECG) findings)
Timepoint [1] 335997 0
-Adverse events monitored from the time of study drug administration on Day 1 through Day 9 (+/- 2) after the last dose of study drug.
-Safety Lab parameters at Screening, Days -1, 2, 4 and End of study (EOS)
-Vital signs at Screening, Day-1, pre-dose (within 2h), and at 1, 2, 3, 8, 12 hours (each +/-10min), and 24, 48 hours (both +/- 30 minutes) post-dose, Day5, and EOS
-ECG's at Screening, pre-dose (within 2h), and at 3, 8, 12, 24 and 48hours post-dose, and EOS.

Primary outcome [2] 336312 0
To evaluate the safety and tolerability of single oral doses (Food Effect) of MRX-5 Tablets in healthy adult subjects.

Incidence and severity of treatment-emergent adverse events (TEAEs) will be assessed for severity and causality (relationship of event to the investigational product) by the study investigator using the specified definitions.
Common Terminology Criteria for Adverse Events (CTCAE) (V5.0) as 5 grades.
- Changes in clinical laboratory parameters including blood tests for complete blood count, coagulation, serum chemistry, and urinalysis.
- Change in vital signs measurements. Vital signs include measurement of heart rate (HR) respiration rate (RR), systolic and diastolic blood pressure (BP) and body temperature.
BP and HR will be measured by an automated BP Machine, RR is a manual calculation where the staff member will count the rise/fall of the chest and temperature will be measured by a digital tympanic thermometer
- Changes in the electrocardiogram (ECG) findings)
Timepoint [2] 336312 0
Adverse events monitored from the time of study drug administration on Day 1 through Day 16 (+/- 2) after the last dose of study drug.
-Safety Lab parameters at Screening, Days -1, 2, 4, 7, 9, 11 and D16[ End of study (EOS)]
-Vital signs at Screening, Day-1, pre-dose (within 2h), and at 1, 2, 3, 8, 12 hours (each +/-10min), and 24, 48 hours (both +/- 30 minutes) post-dose, Day 12, and EOS
-ECG's at Screening, pre-dose (within 2h), and at 3, 8, 12, 24 and 48hours post-dose, and EOS.
Primary outcome [3] 336313 0
To assess the safety and tolerability of multiple oral doses of MRX-5 Tablets in healthy adult subjects.

Incidence and severity of treatment-emergent adverse events (TEAEs) will be assessed for severity and causality (relationship of event to the investigational product) by the study investigator using the specified definitions [Common Terminology Criteria for Adverse Events (CTCAE) (V5.0) as 5 grades]
- Changes in clinical laboratory parameters including blood tests for complete blood count, coagulation, serum chemistry, and urinalysis.
- Change in vital signs measurements. Vital signs include measurement of heart rate (HR) respiration rate (RR), systolic and diastolic blood pressure (BP) and body temperature.
BP and HR will be measured by an automated BP Machine, RR is a manual calculation where the staff member will count the rise/fall of the chest and temperature will be measured by a digital tympanic thermometer
- Changes in the electrocardiogram (ECG) findings)
Timepoint [3] 336313 0
Adverse events monitored from the time of study drug administration on Day 1 through Day 16 (+/- 2) after the last dose of study drug.
-Safety Lab parameters at Screening, Days -1, 2, 4, 6, 8, 10, 12 and 16[ End of study (EOS)]
-Vital signs at Screening, Day-1, pre-dose from Day 1 until Day 10, post dose of the last dose , Day 13 and Day 16( EOS)
-ECG's at Screening, pre-dose (within 2h), and at 1, 2, 6, 24 hours post dose on Days 1, 5, 10 and 16 (EOS)
Secondary outcome [1] 426440 0
To characterize the pharmacokinetic (PK) profile of MRX-5 in healthy adult subjects following single dose

PK parameters will be derived from blood concentrations of MRX-5
Cmax (mg/L), Cmin (mg/L), Tmax (h), AUC0-t (mg·h/L), AUC0-12h (mg·h/L), AUC0-24h (mg·h/L), AUC0-inf (mg·h/L), t1/2 (h), MRT (0-infinity) (h), CLz/F (L/h), Vz/F (L)

Urine Samples: CLr (L/h), UA0-24h (mg), UA0-48h (mg)
Timepoint [1] 426440 0
Blood samples collection for PK analysis: Days 1,2,3,4 5

Urine samples for collection PK analysis: Days 1, 2, 3
Secondary outcome [2] 427823 0
To characterize the pharmacokinetic (PK) profile of MRX-5 in healthy adult subjects following single dose (Food Effect)

PK parameters will be derived from blood concentrations of MRX-5
Cmax (mg/L), Cmin (mg/L), Tmax (h), AUC0-t (mg·h/L), AUC0-12h (mg·h/L), AUC0-24h (mg·h/L), AUC0-inf (mg·h/L), t1/2 (h), MRT (0-infinity) (h), CLz/F (L/h), Vz/F (L)

Urine Samples: CLr (L/h), UA0-24h (mg), UA0-48h (mg)
Timepoint [2] 427823 0
Blood samples collection for PK analysis: Day 1,2,3,4,5. For subjects in Part 1 Cohort 7, blood samples for PK analysis will also be collected on Day 8 (+3 Days) at time points as described above.
Urine samples for collection PK analysis: Day 1, 2,3. For subjects in Part 1 Cohort 7, urine samples for PK analysis will also be collected on Day 8 (+3 days) at time points as described above.
Secondary outcome [3] 427824 0
To characterize the pharmacokinetic (PK) profile of MRX-5 in healthy adult subjects following multiple dose.
PK parameters will be derived from blood concentrations of MRX-5: Cmax,ss (mg/L), Cmin,ss (mg/L), Cavg,ss, Tmax (h), AUC0-t (mg·h/L), AUC0-12h,ss (mg·h/L), AUC0-inf (mg·h/L), AUCtau,ss (mg·h/L), t1/2, ss (h), MRTss (h), Rac, DF(%), N99%, CLss (L/h), Vz,ss (L)
Urine Samples: Ae0-24h (mg), Ae0-48h (mg)
Timepoint [3] 427824 0
Blood samples collection for PK analysis: From Day 1 Pre-dose within 2 h though 96 hours post-dose.
Urine samples for collection PK analysis: From Pre-dose within 2 h though 48 hours post-dose.

Eligibility
Key inclusion criteria
1. Male or female, between 18 and 55 years of age, inclusive, at the time of Screening.
2. Body weight greater than or equal to 45 kg and lesser than or equal to 100 kg and body mass index (BMI) greater than or equal to 18 and lesser than or equal to 32 kg per meter square at the
time of Screening.
3. In good health, as determined by the Investigator based on a medical evaluation including medical history, vital signs, physical examination, laboratory tests and cardiac monitoring.
4. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator agrees and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
5. Female subjects must be non-pregnant and non-lactating.
6. Female subjects must be of non-childbearing potential, or agree to use an acceptable method(s) of contraception and must not donate any eggs from signing ICF and for at least 90 days after the last dosing, and have negative pregnancy test results at Screening (serum) and Admission (urine).
7. Male subjects with female partners of reproductive potential must agree to practice abstinence or to use a condom (male subject) in addition to an acceptable barrier method (female partner) of contraception and must not donate sperm from signing ICF and for at least 90 days after the last dosing.
8. Capable of giving signed informed consent which includes compliance with the schedule, requirements, and restrictions of the study.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Use of tobacco or nicotine products more than 5 units/week, in any form, within 30 days prior to study drug administration on Day 1.
2. Routine consumption of prescription within 14 days prior to study drug administration on Day 1 or consumption of over-the-counter [OTC] medication, vitamin, mineral, grapefruit, or dietary supplement within 7 days prior to study drug administration.
3. Blood pressure (BP) greater than 140/90 mmHg or below 85/40 mmHg (seated). BP out of range may be allowed if considered not clinically significant by the Investigator.
4. History of drug or alcohol abuse in the previous 2 years (Defined excessive alcohol intake as regular consumption over 14 units per week [female] or 21 units per week [male] at least).
5. Positive pre-study drug or alcohol & smoking screen on Day-1.
6. Positive test results for hepatitis B surface antigen, antibody to hepatitis B core antigen, hepatitis C virus antibody, anti–HIV type 1 antibody, and COVID-19.
7. Any history of allergic drug reactions; exceptions may be granted on a case-by-case basis upon agreement of the PI and the Medical Monitor.
8. History of vaccination within 30 days prior to study drug administration on Day 1, or have vaccination intentions during the study or within 30 days end of the study.
9. Any clinical suggestion or family history of renal disease such as polycystic kidney disease, medullary sponge kidney, glomerulonephritis, or any other significant renal symptoms and signs such as clinically significant hematuria, pyuria, proteinuria, glycosuria, and or pathologic crystals findings in the urinalysis.
10. Administration of another investigational medication within 30 days (or 5 half-lives, whichever is longer) prior to study drug administration.
11. Participation in an investigational device study within 30 days prior to study drug administration.
12. Venous access considered inadequate for PK sample collection.
13. Any condition that might interfere with study drug absorption or elimination, such as hepato-biliary disease, surgery of the small intestine, cholecystectomy, or gastrointestinal disease (e.g., nausea, vomiting, diarrhea).
14. Loss or donation of blood greater than 500 mL, or plasma donation within 30 days prior to study drug administration.
15. ECG abnormalities outside of accepted ranges and considered to be clinically significant. Subjects with QTcF greater than 450 msec (if male) or greater than 470 msec (if female) will be excluded.
16. Is an employee or family member of the investigator or study site personnel.
Subjects meeting the following criteria will be excluded from study Part 1, Cohort 7:
17. Inability or unwillingness to consume a standard high-fat meal, as described in FDA Guidance for fed vs. fasted PK studies

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)
For each Part of the study, after informed consent has been obtained and study eligibility
established, the Pharmacist or designee will obtain the Dose Cohort and study drug assignment (MRX-5 or placebo) from a predetermined randomization scheme.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomization will be utilized for this study. Registered SAS version 9.4 will be used.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Descriptive statistical analysis: Registered SAS version 9.4 or greater
Pharmacokinetic analyses: PhoenixTM WinNonlin(Version 8.4 or higher, Pharsight Corporation)

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/11/2023
Actual
17/11/2023
Date of last participant enrolment
Anticipated
5/06/2024
Actual
Date of last data collection
Anticipated
20/06/2024
Actual
Sample size
Target
84
Accrual to date
52
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 314711 0
Commercial sector/Industry
Name [1] 314711 0
Shanghai MicuRx Pharmaceutical Co., Ltd.
Country [1] 314711 0
China
Primary sponsor type
Commercial sector/Industry
Name
Shanghai MicuRx Pharmaceutical Co., Ltd.
Address
No.53, Aidisheng Rd, Pudong District, Shanghai, China, 201203
Country
China
Secondary sponsor category [1] 316680 0
Commercial sector/Industry
Name [1] 316680 0
Novotech Australia Pty Limited
Address [1] 316680 0
Level 3, 235 Pyrmont Street, Pyrmont, NSW 2009, Australia
Country [1] 316680 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313720 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 313720 0
Ethics committee country [1] 313720 0
Australia
Date submitted for ethics approval [1] 313720 0
06/09/2023
Approval date [1] 313720 0
03/10/2023
Ethics approval number [1] 313720 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129134 0
Dr Christina Chang
Address 129134 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 129134 0
Australia
Phone 129134 0
+61 385939800
Fax 129134 0
Email 129134 0
[email protected]
Contact person for public queries
Name 129135 0
Hong Yuan
Address 129135 0
Shanghai MicuRx Pharmaceutical Co., Ltd. No.53, Aidisheng Rd, Pudong District, Shanghai, China 201203
Country 129135 0
China
Phone 129135 0
+86 13818789969
Fax 129135 0
Email 129135 0
[email protected]
Contact person for scientific queries
Name 129136 0
Christina Chang
Address 129136 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 129136 0
Australia
Phone 129136 0
+61 1800 243 733
Fax 129136 0
Email 129136 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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.