A Phase 1 Randomized, Placebo-Controlled, Single & Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of GLY-200 in Healthy Adult Subjects

Phase 1

Completed

• Conditions: Type 2 Diabetes; Metabolic and Endocrine - Diabetes

• Registration Number: ACTRN12621000800820
• Lead Sponsor: Glyscend Pty Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-24
• Study Completion: 2022-03-28
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 64

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 p

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) pr

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary outcome is the safety and tolerability of GLY-200.<br><br>Adverse events will be assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAEv 5.0).[Within the SAD component of the study, assessments will be conducted at baseline, 2, 4 and 6 hours post dose and 7 days post dose.<br><br>Within the MAD component of the study, assessments will be conducted at baseline, 2, 4 and 6 hours post dose on the first day of dosing, daily on each day of dosing and 7 days post last dose.<br>]

Secondary Outcome Measures

Name	Time	Method
A variety of exploratory markers will be analysed from stool, urine and plasma. These include (but will not be limited to): <br>Stool/Faecal analysis (boron analysis, calprotectin)<br><br><br>[These exploratory endpoints will be assessed in the MAD cohorts at baseline, Day 7 and Day 14 of the protocol. <br><br>];Urine analysis (phosphate, oxalate, calcium, boron)<br><br><br>[These exploratory endpoints will be assessed in the MAD cohorts at baseline, Day 7 and Day 14 of the protocol. ];Plasma (Bile acids, cholesterol, HDL/LDL, uric acid)<br>[These exploratory endpoints will be assessed in the MAD cohorts at baseline, Day 7 and Day 14 of the protocol. ]