None listed
Conditions
Brief summary
This research is investigating a naturally occurring compound called N-acetyl-D-mannosamine monohydrate (ManNAc). ManNAc is a sugar (monosaccharide) which is found in humans. Once in the body, ManNAc is converted to another compound called N-acetylneuraminic acid (Neu5Ac) which plays a role in the synthesis and maintenance of muscle; specifically, it facilitates a process called ‘sialylation’. It is being studied as a supplement drug to treat a condition known as GNE myopathy, a rare genetic disease which is characterised by progressive skeletal muscle wasting (atrophy) caused by a lack of sialylation. In patients with GNE myopathy, this wasting and weakness of muscle affects movement and other bodily functions resulting in disability, wheelchair use and/or incapacitation. Previous studies have shown that the administration of ManNAc can replace the important compounds that patients with GNE myopathy are lacking, and therefore may be useful in treating the disease. While supplementation with ManNAc is a promising treatment for patients with GNE myopathy, additional information on how to best administer this sugar-like compound is needed. Two new formulations have been developed; a chewable tablet formulation and a gastroretentive tablet formulation. This study is therefore being conducted to investigate how ManNAc is absorbed into the body when administered as the chewable tablet formulation and the floating tablet formulation, compared to the current oral solution. This information will provide pivotal data to guide the further development of ManNAc treatment strategies for patients with GNE myopathy.
Interventions
Investigational Product
N-acetyl-D-mannosamine (ManNAc)
Study Treatments
Treatment A: 1000 mg ManNAc oral solution, administered as a single oral dose (1000 mg in 200 mL water).
Treatment B: 990 mg ManNAc chewable tablets, administered as a split oral dose (1 x 330 mg tablet every hour).
Treatment C: 1000 mg ManNAc gastroretentive tablets, administered as a single oral dose (4 x 250 mg tablets).
Treatment will be administered under fasting conditions according to a open-label, randomised, th
Investigational Product N-acetyl-D-mannosamine (ManNAc) Study Treatments Treatment A: 1000 mg ManNAc oral solution, administered as a single oral dose (1000 mg in 200 mL water). Treatment B: 990 mg ManNAc chewable tablets, administered as a split oral dose (1 x 330 mg tablet every hour). Treatment C: 1000 mg ManNAc gastroretentive tablets, administered as a single oral dose (4 x 250 mg tablets). Treatment will be administered under fasting conditions according to a open-label, randomised, three-arm, crossover design. An Investigator will supervise self-administration of ManNAc treatments by study participants. Each study period will be separated by a washout period of at least 7 days between treatment administrations.
Sponsors
University of South Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male and aged 18-59 years, inclusive. 2. Body mass index (BMI) is between 18.0 – 30.0 kg/m^2 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.
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 ingredients within the formulations 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 dosing in Period 1. 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 dosing in Period 1. 5. Unable or unwilling to refrain from the use of medications, including complementary therapies and supplements, within 5 half-lives of, or for 24 h prior to dosing (whichever is longer) until completion of all study procedures within each study period. 6. Major surgery within 4 weeks prior to the screening evaluation, or planned surgery prior to completion of all study procedures. 7. Donation of blood or blood products of 470 mL or greater within 12 weeks prior to dosing in Period 1, and/or unable or unwilling to refrain from donation from the screening evaluation until completion of all study procedures. 8. History or current evidence of alcohol abuse and/or unable or unwilling to refrain from alcohol consumption for 24 h prior to dosing 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. 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 dosing 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 dosing until completion of all study procedures in each study period. 12. Unable or unwilling to refrain from food intake from 10 h prior to dosing until the 4 h timepoint 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 to dosing until the 4 h timepoint in each study period. 14. Unable or unwilling to remain seated in an upright position from immediately prior to dosing until the 4 h timepoint in each study period. 15. Unable or unwilling to be confined to the UniSA Clinical Trial Facility for 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 complier or unlikely to attend specified study days.
Outcome results
None listed