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Trial registered on ANZCTR


Registration number
ACTRN12621000800820
Ethics application status
Approved
Date submitted
7/04/2021
Date registered
24/06/2021
Date last updated
16/12/2022
Date data sharing statement initially provided
24/06/2021
Date results information initially provided
16/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 Randomized, Placebo-Controlled, Single & Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of GLY-200 in Healthy Adult Subjects
Scientific title
A Phase 1 Randomized, Placebo-Controlled, Single & Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of GLY-200 in Healthy Adult Subjects
Secondary ID [1] 303785 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 321283 0
Condition category
Condition code
Metabolic and Endocrine 319069 319069 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 320090 0
Treatment: Drugs
Comparator / control treatment
The placebo capsules are opaque shells filled with microcrystalline cellulose to a weight comparable to the active capsules.
Control group
Placebo

Outcomes
Primary outcome [1] 326960 0
The primary outcome is the safety and tolerability of GLY-200.

Adverse events will be assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAEv 5.0).
Timepoint [1] 326960 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.

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.
Secondary outcome [1] 393305 0
A variety of exploratory markers will be analysed from stool, urine and plasma. These include (but will not be limited to):
Stool/Faecal analysis (boron analysis, calprotectin)
Timepoint [1] 393305 0
These exploratory endpoints will be assessed in the MAD cohorts at baseline, Day 7 and Day 14 of the protocol.

Secondary outcome [2] 397209 0
Urine analysis (phosphate, oxalate, calcium, boron)
Timepoint [2] 397209 0
These exploratory endpoints will be assessed in the MAD cohorts at baseline, Day 7 and Day 14 of the protocol.
Secondary outcome [3] 397210 0
Plasma (Bile acids, cholesterol, HDL/LDL, uric acid)
Timepoint [3] 397210 0
These exploratory endpoints will be assessed in the MAD cohorts at baseline, Day 7 and Day 14 of the protocol.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

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)
An unblinded trained pharmacist will be responsible for the dispensing of study treatments in order to maintain blinding.
A statistician will be responsible for generating a randomization schedule before the study starts.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features

Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/06/2021
Actual
13/08/2021
Date of last participant enrolment
Anticipated
Actual
3/03/2022
Date of last data collection
Anticipated
Actual
28/03/2022
Sample size
Target
64
Accrual to date
Final
64
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 308188 0
Commercial sector/Industry
Name [1] 308188 0
Glyscend Pty Ltd
Country [1] 308188 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Glyscend Pty Ltd
Address
Level 9, 31 Queen St, Melbourne, Victoria 3000
Country
Australia
Secondary sponsor category [1] 308966 0
None
Name [1] 308966 0
Address [1] 308966 0
Country [1] 308966 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308171 0
Bellberry Limited
Ethics committee address [1] 308171 0
123 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [1] 308171 0
Australia
Date submitted for ethics approval [1] 308171 0
05/05/2021
Approval date [1] 308171 0
24/06/2021
Ethics approval number [1] 308171 0

Summary
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).
Trial website
Trial related presentations / publications
Public notes
A screening number will be allocated to each volunteer who provides informed consent, so that volunteers can be identified without making assumptions about their subsequent eligibility for the trial.
The details of labelling and a blinding/unblinding plan will appear in a separate pharmacy manual.
If a volunteer fails screening and is not randomised, or discontinues from the trial, the screening number will not be reused.
One repeat test of an individual screening assessment (e.g., laboratory tests) is allowed at the investigator’s discretion. If appropriate, subjects who fail screening may be completely re-screened once with a new screening number.
Participants will be blinded to treatment assignment (GLY-200 or placebo). Study drug will be prepared for administration by an unblinded pharmacist and administered by blinded personnel at the study site.
Participant eligibility will be established before randomization.
The randomisation schedules will be maintained under controlled access.

Contacts
Principal investigator
Name 109790 0
Prof Christopher Rayner
Address 109790 0
The University of Adelaide
Adelaide Health & Medical Sciences, floor 5,
250 North Terrace
Adelaide, South Australia, 5000
Country 109790 0
Australia
Phone 109790 0
+61 8 83136693
Fax 109790 0
Email 109790 0
chris.rayner@adelaide.edu.au
Contact person for public queries
Name 109791 0
Dr Melissa Byrne
Address 109791 0
Level 9, 31 Queen St
Melbourne, Victoria 3000
Country 109791 0
Australia
Phone 109791 0
+61 3 96570700
Fax 109791 0
Email 109791 0
mbyrne@glyscend.com
Contact person for scientific queries
Name 109792 0
Dr Melissa Byrne
Address 109792 0
Level 9, 31 Queen St
Melbourne, Victoria 3000
Country 109792 0
Australia
Phone 109792 0
+61 3 96570700
Fax 109792 0
Email 109792 0
mbyrne@glyscend.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseFirst-in-human study of a pharmacological duodenal exclusion therapy shows reduced postprandial glucose and insulin and increased bile acid and gut hormone concentrations.2023https://dx.doi.org/10.1111/dom.15066
N.B. These documents automatically identified may not have been verified by the study sponsor.