None listed
Conditions
Brief summary
This is a Phase 1a single ascending dose (SAD) escalation and multiple ascending dose (MAD) escalation study, single centre, placebo controlled, randomized, study to assess safety and tolerability of oral GLY-200 in healthy volunteers. The study consists of two parts: Part 1. single ascending dose (SAD) escalation (3-4 cohorts), and; Part 2 multiple ascending dose (MAD) escalation (3-4 cohorts).
Interventions
The route of administration of the drug is oral (capsules).
Single Ascending Dose
The starting dose in the first cohort is one dose of 0.5g per day
The dose will be up titrated over 4 cohorts; cohort 2 = 1.5g per day; cohort 3 = 4.0g per day; cohort 4 = 8.0g per day.
The maximum administered dose will be decided based on tolerability assessments through out the protocol.
Multiple Ascending Dose
The starting dose in the first cohort is one dose of 1.5g per day,
The dose will be up titrate
The route of administration of the drug is oral (capsules). Single Ascending Dose The starting dose in the first cohort is one dose of 0.5g per day The dose will be up titrated over 4 cohorts; cohort 2 = 1.5g per day; cohort 3 = 4.0g per day; cohort 4 = 8.0g per day. The maximum administered dose will be decided based on tolerability assessments through out the protocol. Multiple Ascending Dose The starting dose in the first cohort is one dose of 1.5g per day, The dose will be up titrated over 4 cohorts; cohort 2 = one dose 4.0g per day; cohort 3 = two doses of 4.0g total 8.0g per day; cohort 4 = three doses of 4.0g total 12.0g per day. The duration of the chronic administration is 5 days per cohort with a 9 day follow up. Dose titration and maximum administered dose will be decided based on review of safety data from both the SAD cohorts and preceding MAD cohorts. The MAD component of the study will only occur after review of all available safety and tolerability data in the SAD cohorts as approved by the Safety Review Committee. The SAD and MAD components of the study will include different participants. The protocol will be conducted within a phase 1 unit and administration of capsules will be supervised throughout the protocol.
Sponsors
Glyscend Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female, greater than or equal to 18 and less than or equal to 65 years old at the time of screening, with BMI greater than and equal to 18.0 and less than 32kg/m2 2. Subjects must be in good general health, with no significant medical history, have no clinically significant abnormalities in general physical examination, vital signs, laboratory tests (haematology, urinalysis, blood chemistry, coagulation function), and 12-lead ECG as judged by the investigator at screening and baseline. If necessary, one repeat may be performed at the discretion of the investigator and the reason for repeat must be documented clearly. 3. Use of less than 5 tobacco or nicotine-containing products daily for 1 month prior to screening and able to abstain from smoking during the trial. 4. Healthy as defined by: a. the absence of clinically significant illness and surgery within 12 weeks prior to administration. Subjects experiencing nausea within 24 hours pre-administration will be carefully evaluated for upcoming illness/disease. Inclusion pre-administration is at the discretion of the investigator. b. the absence of clinically significant history of neurological, endocrine, cardiovascular, pulmonary, haematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease, including, but not limited to pancreatitis, hepatitis B or C, HIV, swallowing disorders, and gastroesophageal reflux disease (at least 1 episode per week). c. the absence of clinically significant history of gastric or peptic ulcer, small bowel resection (except if related to appendectomy), intestinal stricture (e.g., Crohn's disease), intestinal obstruction or high risk of intestinal obstruction including suspected small bowel adhesions and prior history of major abdominal surgeries. d. the absence of clinically significant history or known presence of oesophageal anatomic abnormalities (e.g., webs, diverticula, rings), dysphagia, gastroparesis, and malabsorption. e. the absence of history of gastric bypass, any other gastric surgery and intragastric balloon. f. the absence of history of angina, coronary bypass, and myocardial infarction within 6 months prior to administration. g. the absence of history of abdominal radiation treatment. h. the absence of history of cancer within the past 5 years, except adequately-treated localized basal cell skin cancer. 5. Capable of consent, and written informed consent signed prior to entry into the study 6. Subjects must be willing to consume standard meals; meals will be provided 3 times a day, approximately 6 hours apart by the clinical centre 7. Subjects must have the ability and willingness to attend the necessary visits to the study centre 8. Fasting blood glucose levels 3.0 – 5.4 mmol/L and HbA1c less than 6.0% at screening. 9. Male subjects with female partners of childbearing potential must comply with the following contraception requirements from the time of first dose of study medication until 90 days after the last dose of study medication (i.e., one sperm cycle): a. Vasectomy with documentation of azoospermia. b. Male condom plus partner use of one of the contraceptive options below: i. Injectable, or implantable progestogen-only hormonal contraceptives ii. Intrauterine device or intrauterine system iii. Contraceptive vaginal ring iv. Percutaneous contraceptive patches Female subjects of non-childbearing potential must meet at least one of the following criteria: d. Achieved postmenopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicular stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal women; e. Have undergone a documented hysterectomy and/or bilateral oophorectomy; f. Have medically confirmed ovarian failure. All other female subjects (including women with tubal ligations and women who do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential and must be using effective forms of contraception. Women must not be pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin [hCG] test), or lactating. PLEASE NOTE: ORAL CONTRACEPTION IS NOT ALLOWED (and is exclusionary) IN THIS STUDY AS THE STUDY DRUG (GLY-200) MAY REDUCE THE EFFECTIVENESS OF THE ORAL CONTRACEPTION DUE TO POTENTIAL DISRUPTION on GI (Small Intestine) ABSORPTION 10. QT interval corrected using the Fridericia method (QTcF) less than or equal to 450 msec for males and less than or equal to 470 msec for females at screening and on Day 1, prior to dose administration (the mean of triplicate measurements will be used to determine eligibility). 11. Evidence of normal renal function, as defined by a calculated creatinine clearance greater than or equal to 90 mL/min using the Cockcroft-Gault equation 12. Adequate coagulation laboratory assessments (i.e., within normal reference range values) at screening, in the opinion of the Investigator.
Exclusion criteria
1. History of clinically significant endocrine, neurological, cardiovascular, haematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases 2. Mentally or legally incapacitated, has significant emotional problems at the time of Screening Visit or expected during the conduct of the study, or has severe, active psychiatric conditions that require ongoing treatment, or that would impact the subject’s ability to participate in the trial in the opinion of the Investigator. 3. Severe infections, injuries or major surgeries and prior history of major abdominal surgeries (as determined by the investigator) within 4 weeks prior to screening or intend to undergo any surgery during the trial. 4. Use of a live vaccine within 30 days prior to screening or anticipated need for a live vaccine during the study or for 30 days following the last dose of study drug. 6. History of bleeding associated with procedures such as endoscopy or phlebotomy; or use of medications such as nonsteroidal anti-inflammatory drugs (NSAIDS) or aspirin within 28 days prior to screening or planned use during the study. 7. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV). 8. Any history of gastrointestinal disease including inflammatory bowel disease, toxic megacolon, dysphagia, gastroesophageal reflux disease (GERD), colon cancer, intestinal stenosis, or fistula. 9. Any GI symptoms occurring greater than or equal to 1 day per week (including gastroesophageal reflux) as per the Digestive health and wellbeing survey questionnaire will be exclusionary. The final decision will be at the discretion of the PI in consultation with the MM if there are any borderline cases or some uncertainty exists during screening. 10. Subjects with a history of severe allergy to any drug, food, toxin or other exposure. 11. Clinically significant electrocardiogram (ECG) abnormalities or vital sign abnormalities 12. Screening/baseline systolic BP greater than or equal to 160 mmHg or less than 90 mmHg; diastolic BP greater than or equal to 95 mmHg or less than 50 mmHg; resting heart rate less than 45 or greater than 100 bpm, on a single measurement (can repeat 2 more times if necessary, and use the average of the 3 values to determine the subject’s eligibility) following at least 5 minutes of rest. 13. History of significant alcohol abuse within one year prior to screening or History of regular alcohol consumption in the past 3 months prior to screening, as defined by: a. Australian Guidelines, exceeding an average weekly intake of 10 standard drinks and no more than 4 standard drinks on any one day for males or females; one standard drink=10 grams of alcohol (equivalent to 12.5 mL of pure alcohol, 285 mL of full-strength beer, 375 mL of mid-strength beer, 425 mL of low-strength beer, 100 mL of wine, or 30 mL of 40% alcohol spirits). b. A positive alcohol breath test at screening or Day-1. 14. History of illicit or prescription drug abuse or addiction within one year of screening, or positive urine drug screen at screening or Day-1. The urine drug screen may be repeated at the discretion of the investigator and the reason for repeat needs to be documented clearly (e.g., suspicion of false positive due to diet). 15. Participation in a clinical trial involving the administration of an investigational or marketed drug or device within 30 days (90 days for biologics) prior to the first administration or concomitant participation in an investigational study involving no drug or device. 16. Use of any prescription medication within 14 days, or over-the-counter medicine, herbal remedy or nutritional supplement within 7 days prior to screening, or within 5 half-lives of any drugs whichever is longer during screening visit, or plan to use any medicine during the trial, with the exception of hormonal contraceptives for female volunteers. 17. History of severe digestive system disease or having digestive disease currently or within a month of screening. 18. Blood donation or loss of more than 200 mL of blood within 1 month of screening; or blood donation or loss of more than 400 mL of blood within 3 months of screening; or received blood within 8 weeks of screening. 19. Clinically significant laboratory abnormalities including: a. Impaired renal function at Screening estimated based on the Cockcroft-Gault equation defined as GFR<90mls/min b. ALT, AST, or total bilirubin level greater than1.5× upper limit of normal (ULN) during screening/baseline visits or as deemed clinically significant by the investigator. Note: Gilbert’s syndrome is allowable as clearance by glucuronidation is not relevant for this study drug based on its absence of systemic absorption. c. Glycosylated haemoglobin (HbA1c greater than or equal to 6.0% which is equivalent to greater than or equal to 48 mmol/mol). 20. History of any previous abdominal surgery including endoscopic keyhole surgery or lap band procedure, surgical resection of the stomach, small or large intestine (excluding appendectomy or cholecystectomy, or of any other risk of abdominal adhesions or obstruction. 21. Clinically significant symptoms of nausea, vomiting, bloating, diarrhea, flatulence, abdominal pain, or constipation. 22. Subjects who are unlikely to comply with the study protocol OR those who would not be suitable candidates for participation in the opinion of the investigator including any reason which, in the opinion of the Qualified Investigator, would prevent the subject from participating in the study. 23. Any other conditions (e.g., not suitable for venous access) or laboratory abnormality that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results and, at the discretion of the investigator, makes the subject inappropriate for entry into this study.
Outcome results
None listed