Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001127998
Ethics application status
Approved
Date submitted
3/09/2020
Date registered
30/10/2020
Date last updated
1/12/2021
Date data sharing statement initially provided
30/10/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
A three-dose study of N-Acetyl-D-Mannosamine Monohydrate (ManNAc) in fasting conditions to determine the difference in absorption when dosed differently in healthy male participants
Scientific title
An open-label, randomised, three-arm crossover study to assess the absorption characteristics of different dosing strategies for ManNAc in healthy adult males
Secondary ID [1] 302055 0
ManNAc.01
Secondary ID [2] 302057 0
Nil.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
GNE Myopathy 318652 0
Condition category
Condition code
Musculoskeletal 316671 316671 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 316672 316672 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an open-label, randomised, three-arm crossover study which will be conducted in twelve healthy adult males. Consented and eligible participants will present to the Clinical Trial Facility on the morning of each study period after an overnight fast.

Participants will be randomised into one of 3 treatment sequences (ABC, CBA or CAB). A 7-day washout period will occur between each treatment period. The interventions will be as follows:

Treatment A: A total of 4 g ManNAc will be administered as one dose at 0 hours.
Treatment B: A total of 4 g ManNAc will be administered as split 1 g doses at 0, 1, 2 and 3 hours.
Treatment C: A total of 4 g ManNAc will be co-administered with 1 g table salt as one dose at 0 hours.

All treatments will be orally administered as a solution.
Intervention code [1] 318359 0
Treatment: Drugs
Comparator / control treatment
This is a three period crossover study where the reference treatment will be the bioavailability of a single dose of 4 g of ManNAc in the fasted state. This will be compared to the bioavailability of ManNAc when administered as split 1 g doses and 4 g ManNAc administered with dietary salt.
Control group
Active

Outcomes
Primary outcome [1] 324796 0
Determination of comparitive pharmacokinetics of ManNAc after oral administration under different treatment conditions.

Pharmacokinetic parameters including maximum observed plasma concentrations (Cmax), time to reach maximum observed plasma concentrations (Tmax), apparent terminal plasma elimination rate constant (Ke), area under the plasma concentration versus time curve from time zero to the time of the last measurable concentration (AUCt) and from time zero to infinite time (AUCinf), and half-life (T1/2) will be calculated form plasma concentration data.
Timepoint [1] 324796 0
Treatment A: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 and 12 h post-dose

Treatment B: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 11, 13 and 15 h post-dose

Treatment C: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 and 12 h post-dose.
Secondary outcome [1] 385775 0
Determination of safety profile of ManNAc after oral administration to healthy male participants.
Timepoint [1] 385775 0
Clinical laboratory tests (haematology, biochemistry, serology, urinalysis) will be assessed at screening (baseline). Haematology and biochemistry will be re-tested at study Period 3 , prior to discharge from the Clinical Trial Facility.

Vital signs (blood pressure, pulse rate and body temperature) will be assessed at screening (baseline) and each study period at pre-dose, 4 h post-dose and prior to discharge from the Clinical Trial Facility.

Unexpected adverse events will be monitored daily throughout the conduct of the study. I.e from the time informed consent is obtained, through to the follow-up phone call 5-7 days after study period 3. Participants will be prompted to self-report any changes in health.

Eligibility
Key inclusion criteria
1. The participant is a male aged 18-59 years, inclusive.
2. Body mass index (BMI) is between 18-30 kg/m2 with a body weight between 45-120 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 including an electrocardiogram (ECG), physical examination and clinical laboratory assessment).
4. Adequate venous access on their left or right arm to allow for collection of multiple blood samples.
5. The participant is aware of the study procedures and the risks involved, and voluntarily agrees to participate by providing written informed consent.
6. The participant is willing and able to understand the study procedures and communicate effectively with study personnel.
7. The participant is willing to be confined to the Clinical Trial Facility for the specified study days.
Minimum age
18 Years
Maximum age
59 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of clinically significant central nervous system (e.g. seizures), cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions, or history of any conditions that in the opinion of the Medical Officer, may pose an unacceptable level of risk to either the participants ort study staff, may interfere with the interpretation of safety and/or tolerability data obtained in the trial, or may interfere with the absorption, distribution, metabolism, or excretion of the study compound.
2. History of hypersensitivity to ManNAc or dietary salt or in the judgment of the Medical Officer, has a condition that places the participant at increased risk for adverse effects.
3. Consumption of an investigational medication or a new chemical entity within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment.
4. The participant has been treated with ManNAc, sialic acid, intravenous immunoglobulin (IVIG), and/or other supplements containing sialic acid (e.g. St. John’s Wort, sialyllactose) less than 120 days prior to administration of the study compound.
5. Difficulty of refraining from prescription medications and/or over the counter (OTC) products, which in the opinion of the Medical Officer might affect the results of the study or safety of the participant.
6. Donation of blood or blood products in excess of 550 mL within 12 weeks prior to administration of study medication.
7. History or current evidence of alcohol abuse and/or difficulty in abstaining from alcohol for 24 h prior to dose administration until the completion of blood sampling in each study period.
8. History or current evidence of drug abuse, positive urine drug screen during screening, and/or difficulty in abstaining from drugs of abuse throughout the entire study.
9. Difficulty in abstaining from food and/or beverages that contain caffeine or other xanthines (I.e. coffee, tea, cola, energy drinks and chocolate) for 24 h prior to dose administration until the completion of blood sampling in each study period.
10. Major surgery within 4 weeks of screening.
11. Uncontrolled intercurrent illness (i.e. active infection).
12. Tobacco users who are unable to refrain from smoking whilst confined in the Clinical Trial Facility each study day.
13. Difficulty in refraining from food and fluid (excluding water) consumption from 2200 h the night before dosing (I.e. for 10 h prior to dosing) until up to 5 h after the initial dose each treatment period.
14. The participant has specific dietary requirements that prevents the consumption of a standardised meal.
15. 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)
A computer generated randomisation schedule will be prepared.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 0
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Pharamcokinetic parameters will be determined using non-compartmental methods. A linear mixed-effect analysis of variance (ANOVA) model will be used to analyse dose-normalised Ln-transformed pharmacokinetic parameters. The residual error (error mean square) will be used to construct the 90% confidence intervals for the ratio of treatment means. In constructing these 90% confidence intervals, the control treatment (i.e. Treatment A) will be used as the reference. Equivalence will be concluded if the 90% confidence intervals were within the standard regulatory limits of 80-125%. Significance will be set at an a-level of 0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
12/10/2020
Date of last participant enrolment
Anticipated
20/11/2020
Actual
19/10/2020
Date of last data collection
Anticipated
1/12/2020
Actual
18/12/2020
Sample size
Target
20
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 306475 0
Commercial sector/Industry
Name [1] 306475 0
Leadiant Biosciences Inc
Country [1] 306475 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] 306999 0
None
Name [1] 306999 0
Address [1] 306999 0
Country [1] 306999 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306683 0
University of South Australia Human Research Ethics Committee
Ethics committee address [1] 306683 0
Ethics committee country [1] 306683 0
Australia
Date submitted for ethics approval [1] 306683 0
29/06/2020
Approval date [1] 306683 0
20/08/2020
Ethics approval number [1] 306683 0
203235

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

Contacts
Principal investigator
Name 104662 0
Dr Stephanie Reuter Lange
Address 104662 0
University of South Australia
CEA-19, GPO Box 2471
Adelaide, SA, 5001
Country 104662 0
Australia
Phone 104662 0
+61 08 8302 1872
Fax 104662 0
Email 104662 0
[email protected]
Contact person for public queries
Name 104663 0
Louise Massie
Address 104663 0
University of South Australia
CEA-08, GPO Box 2471
Adelaide, SA, 5001
Country 104663 0
Australia
Phone 104663 0
+61 08 8302 2097
Fax 104663 0
Email 104663 0
[email protected]
Contact person for scientific queries
Name 104664 0
Stephanie Reuter Lange
Address 104664 0
University of South Australia
CEA-19, GPO Box 2471
Adelaide, SA, 5001
Country 104664 0
Australia
Phone 104664 0
+61 08 8302 1872
Fax 104664 0
Email 104664 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.