None listed
Conditions
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.
Interventions
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
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.
Sponsors
National Institute of Health - NHGRI Undiagnosed Disease Program
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 59 Years
Healthy volunteers
Yes
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
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
Outcome results
None listed