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Trial registered on ANZCTR


Registration number
ACTRN12619000101189
Ethics application status
Approved
Date submitted
22/01/2019
Date registered
23/01/2019
Date last updated
2/08/2019
Date data sharing statement initially provided
23/01/2019
Date results information initially provided
2/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of a single oral dose of 4 g of N-Acetyl-D-Mannosamine Monohydrate (ManNAc) in each of fasted and fed conditions to determine the differences in absorption of ManNAc with food intake in healthy participants.
Scientific title
A Phase 1, Single Center, Open-Label, Randomized, Two-Period, Two- Arm Crossover Study Of The Bioavailability Of A Single Dose Of N- Acetyl-D-Mannosamine Monohydrate (ManNAc) In A Fasted Condition and A Fed Condition In Healthy Adults
Secondary ID [1] 297127 0
LBI-ManNAc-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
GNE Myopathy 311147 0
Condition category
Condition code
Musculoskeletal 309776 309776 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 309846 309846 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a two-period, two-arm crossover study where the enrolled subjects will receive orally a dose of 4 g of N-Acetyl-D-Mannosamine Monohydrate (ManNAc) in fasted and fed conditions. Consented and eligible subjects will check-in at the clinical unit on Day -1 (i.e. one day before dosing) to start 10 hours of overnight fasting under direct supervision of the site study personnel

The intervention will be as follows:

Fasted Arm: up to 8 female and male subjects will receive orally one dose of 4 g of ManNAc in 200 mL of water for irrigation following 10 hours of fasting (i.e. no food or fluid intake by mouth apart from water which is permitted up to 1 hr before dosing). The subjects will be in the clinical facility while they fast for 10 hours under close supervision of the site personnel to ensure protocol compliance. The dose will be administered under direct supervision of the study personnel and the container dispensed with the study drug will be visually inspected to ensure the total dose is administered.

Fed Arm: up to 8 female and male subjects will receive orally one dose of 4 g of ManNAc in 200 mL of water for irrigation 30 minutes after consuming a high-fat content meal. The high-fat meal will consist of 2 eggs fried in butter, two strips of bacon, two slices of toast with butter, approximately 110 grams of hash brown potatoes and 240 mL of whole milk. The dose will be administered under direct supervision of the study personnel and the container dispensed with the study drug will be visually inspected to ensure the total dose is administered.

After a washout period of 7 days subjects will subsequently receive a dose of 4 g of ManNAc in the opposite arm of the study.
Intervention code [1] 313390 0
Treatment: Drugs
Comparator / control treatment
This is a two period crossover study where the reference condition will be the bioavailability of a single dose of 4 g of ManNAc in the fasted state which will be compared against the bioavability of a single dose of 4 g of ManNAc in a fed state.
Control group
Active

Outcomes
Primary outcome [1] 318734 0
Determination of the bioavailability/pharmacokinetics (AUC (0-inf) and Cmax) via plasma assay of single dose of 4 g of ManNAc immediate release in normal healthy volunteers under both fed and fasted conditions.
Timepoint [1] 318734 0
• Day 1: (baseline) within 30 minutes prior to dose administration
• Day 1: at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, and 12 hours post-dose
• Day 2: at 18, 24, 30, 36 hours post-dose
• Day 3: at 48 hours post-dose
Secondary outcome [1] 365855 0
Characterisation of the pharmacokinetics of Neu5AC (AUC (0-inf) and Cmax) via plasma assay from a single dose of ManNAc immediate release in fed and fasted conditions
Timepoint [1] 365855 0
• Day 1: (baseline) within 30 minutes prior to dose administration
• Day 1: at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, and 12 hours post-dose
• Day 2: at 18, 24, 30, 36 hours post-dose
• Day 3: at 48 hours post-dose
Secondary outcome [2] 365856 0
Determination of safety and tolerability of ManNAc immediate release in normal healthy volunteers under both fed and fasted conditions through the assessment of safety clinical laboratory tests, 12-lead ECGs, vital signs, physical examinations and Adverse Event (AE) monitoring
Timepoint [2] 365856 0
In each of the treatment periods the following assessments will be performed:

*Safety clinical laboratory tests (haematology and blood chemistry) assessed at baseline (Screening and Day -1) and on Day 3 prior to discharge from the unit.

*12-lead ECGs assessed at baseline (Screening and Day -1), Day 1 (2 hr and 10 hr post-dose) and on Day 3 prior to discharge from the unit.

*Vital signs:blood pressure and pulse rate will be assessed at Screening and on Day -1, on Day 1 (pre-dose, 2 hr, 8 hr and 10 hr post-dose), on Day 2 (24 hr and 36 hr post-dose) and Day 3 (48 hr post-dose)

*Vital signs;respiratory rate and oral temperature will be assessed at Screening and on Day -1, on Day 3 prior to discharge from the unit

*Physical Examination: at screening, on Day-1 and on Day 3 prior to discharge from the unit

*Adverse Events (AEs): monitored daily throughout the conduct of the study (from the time of Informed Consent is signed through to the follow up call on Day 8 subsequent to discharge from the unit after Period 2). AEs will be spontaneously reported by the subjects, in response to open question from the study personnel or revealed by observation during the conduct of the study at the clinical site.

Eligibility
Key inclusion criteria
1. The subject is a healthy male or female, 18-59 years of age, inclusive
2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive; and a body weight in the range of 45 to 100 kg
3. Medically healthy without clinically significant (CS) abnormalities at the screening visit or Day -1, including:
4. The subject has voluntarily signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent
5. Females must be of non-childbearing potential (surgically sterile or post-menopausal for at least 1 year) or be practicing a highly effective contraception method from consent to at least 10 days after the last dose of study medication.
6. Males engaging in sexual intercourse with a female partner of childbearing potential must be vasectomized (at least 6 months prior to dosing) or be practicing a highly effective contraception method from consent to at least 10 days after the last dose of study medication.
7. Females of childbearing potential have a negative urine pregnancy test during screening and equal or less than 24 hours prior to study dosing, and are not lactating
8. Negative test for selected drugs of abuse, alcohol, and cotinine at the Screening visit and on Day -1
9. Nonsmoker, defined as not having smoked or used any form of tobacco or nicotine containing products in more than 6 months before screening
10. The subject is willing and able to understand the study procedures, to communicate meaningfully with the study personnel, and to comply with the study protocol
11. Subjects must be willing to be confined at the clinical research center for the protocol- specified study days
Minimum age
18 Years
Maximum age
59 Years
Gender
Both males and females
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 Investigator, may place the subject at an unacceptable risk as a participant in this trial, 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 drugs
2. Participation in a clinical trial or receipt of an investigational medication or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of the medication (whichever is longer) prior to the first dose of study medication
3. Use of prescription or non-prescription medications, including herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or use of St. John’s Wort within 120 days prior to the first dose of study medication
4. Consumption of grapefruit, grapefruit juice, orange juice, Seville oranges, or red wine within 7 days prior to administration of study medication
5. Donation of blood or blood products in excess of 550 mL within 4 weeks prior to administration of study medication
6. Subject has hypersensitivity to ManNAc or components thereof or in the judgment of the investigator, has a condition that places the subject at increased risk for adverse effects
7. Subject 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 study medication
8. Unwillingness to use appropriate contraceptive measures if engaging in sexual intercourse with a female partner of childbearing potential.
9. Major surgery within 4 weeks of screening
10. Uncontrolled intercurrent illness (i.e. active infection)
11. Any other medical or psychiatric illness that could, in the Investigator’s opinion, interfere with the completion of the study procedures specified in this protocol
12. Wishing to become pregnant during study participation or unwilling to use birth control
13. Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Antibody (HCVAb)
14. History of regular alcohol consumption exceeding 7 drinks per week for females and 14 drinks per week for males within 6 months of screening

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 not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated randomisation schedule will be prepared by a statistician prior to study intervention. The randomisation will be stratified by gender such that at least 3 subjects of each gender will be assigned to each sequence (i.e. fed arm vs fasted arm)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
This is a two-period crossover study
Phase
Phase 1
Type of endpoint(s)
Bio-availability
Statistical methods / analysis
A total of at least 12 subjects are targeted to complete both treatment periods and provide the key pharmacokinetic (PK) parameters.
Data will be tabulated by treatment condition (fed and fasted) and presented using both descriptive and inferential statistics where specified.
Safety outcomes will be assessed for all subjects who take at least one dose of study medication. Pharmacokinetic outcomes will be evaluated for all subjects with valid PK parameters for both of the 2 treatment conditions.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 12957 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 25428 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 301688 0
Commercial sector/Industry
Name [1] 301688 0
Leadiant Biosciences, Inc.
Address [1] 301688 0
9841 Washingtonian Blvd, Suite 500
Gaithersburg, MD 20878


Country [1] 301688 0
United States of America
Primary sponsor type
Government body
Name
National Institute of Health - NHGRI Undiagnosed Disease Program
Address
Building 31, Room 4B09
31 Center Drive, MSC 2152
9000 Rockville Pike
Bethesda, MD 20892-2152
Country
United States of America
Secondary sponsor category [1] 301408 0
Commercial sector/Industry
Name [1] 301408 0
Leadiant Biosciences Inc
Address [1] 301408 0
9841 Washingtonian Blvd, Suite 500
Gaithersburg, MD 20878

Country [1] 301408 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302408 0
The Bellberry Human Research Ethics Committee D (EC00444)
Ethics committee address [1] 302408 0
123 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 302408 0
Australia
Date submitted for ethics approval [1] 302408 0
12/12/2018
Approval date [1] 302408 0
07/01/2019
Ethics approval number [1] 302408 0
2018-11-1003

Summary
Brief summary
Background:
Patients with GNE myopathy have muscle weakness and can have difficulty walking . The disease comes from a gene mutation related to the production of a sugar called sialic acid. Researchers think decreased sialic acid may cause the muscle problems. Researchers are testing the drug ManNAc which is a building block of sialic acid. It is a powder that is dissolved in water.

Study Rationale:
Because ManNAc is a simple monosaccharide, there is a possibility that its absorption can be impacted by co-ingestion with other foods. There is, therefore, a need to better understand any potential effects of food on the absorption of ManNAc by comparing the administration of 4 g of ManNAc under fed or fasted conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90138 0
Dr Thomas Polasek
Address 90138 0
CMAX
18a North Terrace
Adelaide SA 5000
Country 90138 0
Australia
Phone 90138 0
+61 (0)8 7088 7900
Fax 90138 0
Email 90138 0
Tom.Polasek@certara.com
Contact person for public queries
Name 90139 0
Mrs Pilar Garzon
Address 90139 0
Avance Clinical Pty Ltd

Level 1
2 Ann Nelson Drive
Thebarton SA 5031
Country 90139 0
Australia
Phone 90139 0
+61 422 345 085
Fax 90139 0
Email 90139 0
pilar.garzon@avancecro.com
Contact person for scientific queries
Name 90140 0
Dr GianFranco Fornasini
Address 90140 0
Leadiant Biosciences Inc

9841 Washingtonian Blvd, Suite 500
Gaithersburg, MD 20878

Country 90140 0
United States of America
Phone 90140 0
+1 301 670 1537
Fax 90140 0
Email 90140 0
Gianfranco.Fornasini@leadiant.com

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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary