Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000394741
Ethics application status
Approved
Date submitted
1/03/2022
Date registered
8/03/2022
Date last updated
6/06/2023
Date data sharing statement initially provided
8/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to determine the absolute oral bioavailability of N-Acetyl-D-Mannosamine Monohydrate (ManNAc) in healthy adult males.
Scientific title
An open-label, randomised, two-arm crossover study to determine the absolute oral bioavailability of ManNAc in healthy adult males
Secondary ID [1] 306495 0
ManNAc.02
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
GNE Myopathy 325361 0
Condition category
Condition code
Musculoskeletal 322745 322745 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 322746 322746 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational Product
N-acetyl-D-mannosamine (ManNAc)

Study Treatments
Treatment A: Single dose of 100 mg ManNAc administered via intravenous injection (5 mL) into an arm vein over approximately 20 minutes.

Treatment B: Single dose of 1000 mg ManNAc administered via oral solution (200 mL).

Treatment will be administered under fasting conditions according to a open-label, randomised, two-arm crossover design. Administration of ManNAc via intravenous injection (Treatment A) will be performed by a Clinical Investigator or a designated PARC Clinical Research staff member. A Clinical Investigator or a designated PARC Clinical Research staff member will supervise self-administration of ManNAc oral solution (Treatment B) by study participants. Dose administration in each study period will be separated by a washout of at least 7 days.
Intervention code [1] 322924 0
Treatment: Drugs
Comparator / control treatment
ManNAc administered via the oral route is the comparator.
Control group
Active

Outcomes
Primary outcome [1] 330550 0
ManNAc and N-Acetylneuraminic acid (Neu5Ac) pharmacokinetic parameters, including:
- Area under the concentration versus time profile from 0 to the last quantifiable concentration (AUClast)
- Maximum observed plasma concentration (Cmax)
- Time to maximum plasma concentration (Tmax)

In addition, where the terminal phase of the concentration-time profile can be determined, the following pharmacokinetic parameters will calculated:
- Terminal rate constant
- Area under the concentration versus time profile extrapolated to infinite time (AUCinf)
- Terminal half-life (T1/2)
- Clearance (CL)
- Volume of distribution (Vd)

Absolute bioavailability will be calculated for each study participant. Pharmacokinetic analysis will be based on uncorrected and baseline-corrected plasma concentrations.
Timepoint [1] 330550 0
Treatment A: Pre-dose (0 h, 10 min and 20 min (coinciding with the end of intravenous injection)), and at the following times relative to the end of the infusion: 5 min, 10 min, 20 min, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 48 h.

Treatment B: Pre-dose (0 h) and at 0.25 h, 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 48 h post-dose.
Secondary outcome [1] 406640 0
Safety parameters such as adverse events, vital signs, electrocardiograms and clinical laboratory tests (haematology, biochemistry)
Timepoint [1] 406640 0
Adverse events will be monitored continuously from Screening until Follow-up (5-7 days after receiving the last study treatment in Study Period 2). Previous studies have found that ManNAc is generally safe and well-tolerated. The most common side effects which have been reported include diarrhea, flatulence (passing wind), and bloating. These side effects have generally been reported at higher ManNAc doses than what is being administered in this study. As a consistent method to prompt reporting of adverse events, participants will be asked a non-leading question prior to dosing and then at 4 h, 12 h, 24 h and 48 h after treatment administration in each study period. Vital signs, including blood pressure, pulse rate, respiratory rate, body temperature and oxygen saturation will be recorded at Screening as well as prior to dosing and then 4 h, 12 h, 24 h and 48 h after treatment administration in each Study Period. Study staff will record all vital sign measurements. Specifically, blood pressure and pulse rate will be measured using a sphygmomanometer, body temperature will be measured using a forehead thermometer, respiratory rate will be measured by manual count and oxygen saturation will be measured using a pulse oximeter. A continual electrocardiogram will occur from pre-dose until 4 h after the end of treatment administration in each Study Period with measurements recorded prior to dosing, and 20 min and 4 h after treatment administration in each Study Period. Blood samples collected for clinical laboratory testing (haematology, biochemistry) will be assessed at screening and after completion of the study procedures in Period 2 (i.e. 48 hours post final study dose).

Eligibility
Key inclusion criteria
1. Male and aged 18-59 years, inclusive.
2. Body mass index (BMI) is between 18.0 – 30.0 kg/m2 with a body weight between 45.0 – 120.0 kg.
3. Medically healthy without any clinically significant abnormalities. Health status will be determined by the participant's medical history with specific attention to: (i) drug history, identifying any known drug allergies or drug abuse, (ii) any chronic use of medication, and (iii) a thorough review of body systems (vital signs, electrocardiogram (ECG), physical examination and clinical laboratory tests).
4. Adequate venous access on their left or right arm to allow for collection of multiple blood samples.
5. Aware of the study procedures and the risks involved, and voluntarily agrees to participate by providing written informed consent.
6. Willing and able to understand the study procedures and communicate effectively with study personnel.
Minimum age
18 Years
Maximum age
59 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or presence of any medical condition that, in the opinion of the Medical Officer, may pose an unacceptable level of risk to participants or study staff, may interfere with the interpretation of safety data obtained in the trial, or may interfere with the absorption, distribution, metabolism, or excretion of ManNAc.
2. History of hypersensitivity to ManNAc or, in the judgment of the Medical Officer, has a condition that places the participant at increased risk for adverse effects.
3. Ingestion of an investigational medication or a new chemical entity within 30 days or 5 half-lives (whichever is longer) prior to treatment administration in Period 1 (i.e. prior to the first dose of the study).
4. Treated with ManNAc, sialic acid, intravenous immunoglobulin (IVIg), and/or other supplement containing sialic acid (e.g. St. John’s Wort, sialyllactose) within 120 days prior to treatment administration in Period 1.
5. Unable or unwilling to refrain from the use of medications, including complementary therapies and supplements, within 5 half-lives of study treatment administration.
6. Major surgery within 4 weeks prior to the screening evaluation, or planned surgery prior to completion of all study procedures in Period 2.
7. Donation of blood or blood products of 470 mL or greater within 12 weeks prior to treatment administration in Period 1, and/or unable or unwilling to refrain from donation from the screening evaluation until completion of all study procedures in Period 2.
8. History or current evidence of alcohol abuse and/or unable or unwilling to refrain from alcohol consumption for 24 h prior to treatment administration until completion of all study procedures in each study period.
9. History or current evidence of drug abuse, positive urine drug screen during screening, and/or unable or unwilling to refrain ingestion of drugs of abuse from the screening evaluation until completion of all study procedures in Period 2.
10. Unable or unwilling to refrain from consuming food and/or beverages that contain caffeine or other xanthines (e.g. coffee, tea, cola, energy drinks and chocolate) for 24 h prior to treatment administration until completion of all study procedures in each study period.
11. Unable or unwilling to refrain from the use of tobacco products for 24 h prior to treatment administration until completion of all study procedures in each study period.
12. Unable or unwilling to refrain from food intake from 10 h prior until 4 h after treatment administration in each study period.
13. Unable or unwilling to refrain from fluid intake, aside from that given as part of study procedures, from 1 h prior until 2 h after treatment administration in each study period.
14. Unable or unwilling to remain seated in an upright position from immediately prior until 4 h after treatment administration in each study period.
15. Unable or unwilling to be confined to the UniSA Clinical Trial Facility for approximately 12 hours on the specified study days and/or attend the other study visits.
16. Dietary requirements that prevent consumption of the standardised study meals.
17. Poor compliers or those who are unlikely to attend specified study days.

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)
Allocation to intervention is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised 1:1 to receive the study treatments according to one or two treatment sequences (AB or BA). The randomisation schedule will be generated using computer-generated block randomisation methods.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Pharmacokinetic analysis will be based on baseline-corrected plasma concentrations of ManNAc and Neu5Ac, Standard pharmacokinetic parameters will be calculated using industry-standard non-compartmental methods.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
26/09/2022
Actual
17/11/2022
Date of last participant enrolment
Anticipated
28/10/2022
Actual
24/01/2023
Date of last data collection
Anticipated
23/12/2022
Actual
21/02/2023
Sample size
Target
6
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 310840 0
Commercial sector/Industry
Name [1] 310840 0
Leadiant Biosciences Inc
Country [1] 310840 0
United States of America
Primary sponsor type
University
Name
University of South Australia
Address
GPO Box 2471, Adelaide SA 5001
Country
Australia
Secondary sponsor category [1] 312095 0
None
Name [1] 312095 0
Address [1] 312095 0
Country [1] 312095 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310405 0
University of South Australia Human Research Ethics Committee
Ethics committee address [1] 310405 0
Ethics committee country [1] 310405 0
Australia
Date submitted for ethics approval [1] 310405 0
22/02/2022
Approval date [1] 310405 0
Ethics approval number [1] 310405 0
Ethics committee name [2] 311605 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [2] 311605 0
Ethics committee country [2] 311605 0
Australia
Date submitted for ethics approval [2] 311605 0
25/05/2022
Approval date [2] 311605 0
16/08/2022
Ethics approval number [2] 311605 0
2022/HRE00117

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

Contacts
Principal investigator
Name 117546 0
Prof Guy Ludbrook
Address 117546 0
PARC Clinical Research Unit
Royal Adelaide Hospital
1 Port Road
Adelaide, SA, 5000
Country 117546 0
Australia
Phone 117546 0
+61 08 7074 1544
Fax 117546 0
Email 117546 0
[email protected]
Contact person for public queries
Name 117547 0
Crystal Eldridge
Address 117547 0
PARC Clinical Research Unit
Royal Adelaide Hospital
1 Port Road
Adelaide, SA, 5000
Country 117547 0
Australia
Phone 117547 0
+61 08 7074 4404
Fax 117547 0
Email 117547 0
[email protected]
Contact person for scientific queries
Name 117548 0
Stephanie Reuter Lange
Address 117548 0
University of South Australia
UniSA Clinical and Health Sciences
CEA-17, GPO Box 2471
Adelaide, SA, 5001
Country 117548 0
Australia
Phone 117548 0
+61 08 8302 1872
Fax 117548 0
Email 117548 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
No data sharing plan is in place for this study.


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.