Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000084785
Ethics application status
Approved
Date submitted
22/12/2021
Date registered
21/01/2022
Date last updated
18/11/2022
Date data sharing statement initially provided
21/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A First-in-Human Phase 1 Study to evaluate the Safety and Tolerability of Single ascending doses of GSBR-1290 in Healthy Adult participants.
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of GSBR-1290 in Healthy Volunteers
Secondary ID [1] 306043 0
GSBR-1290-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 324685 0
Condition category
Condition code
Metabolic and Endocrine 322131 322131 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
GSBR-1290 is an orally available Glucagon-like peptide receptor agonist (GLP-1RA) being developed for the treatment of Type 2 Diabetes Mellitus (T2DM) and obesity. 24 Participants have been dosed to date. 48 Healthy volunteers total will be enrolled in a total of 6 cohorts (Cohorts 1 to 6) in this study. Each Cohort will enroll 8 participants with 6 participants randomized to receive GSBR-1290 and 2 participants randomized to receive placebo. All doses will be supervised and documented by site staff. GSBR-1290 oral capsule will be provided at different ascending dose levels cohorts. Cohorts 1, 2, 3, 5 and 6 will receive doses in the range of 1mg to 540mg of GSBR-1290 and placebo on Day 1 orally. Cohort 4 will receive 90mg, or other dose to be determined by the Safety Review Committee in the range of 1mg to 540mg, GSBR-1290 or placebo administered on Day 1 under fasted conditions and another dose administered on Day 4 under fed conditions with total of 2 doses being administered orally.

Dose levels for each cohort may change based on emerging safety and PK data upon review by the Safety Review Committee (SRC) meeting following each cohort. Cohorts will be does in a sequentially escalating order, unless the SRC determines otherwise in the interest of participant safety. If participants experience any clinically significant AEs during the confinement period, they may remain in the clinical facility for further observation at the discretion of the PI.
Intervention code [1] 322446 0
Treatment: Drugs
Comparator / control treatment
The placebo to match GSBR-1290 are Hydroxypropyl methylcellulose (HPMC) capsules containing hydroxypropyl methylcellulose acetate succinate.
Control group
Placebo

Outcomes
Primary outcome [1] 329900 0
To assess the safety and tolerability of single oral doses of GSBR-1290 in healthy adult volunteers. The parameters assessed for the safety endpoints include:
- Incidence, severity and relationship of Adverse Events/Serious Adverse Events (including withdrawals due to AEs). AEs and SAEs will be assessed for severity and causality (relationship of the event to the investigational product by the study investigator using the specified grading definitions Common Terminology Criteria for Adverse Events.
-Change from baseline in vital signs (systolic and diastolic blood pressure, respiration rate, heart rate and temperature) . Vital sign data will be collected by automatic digital sphygmomanometer, heart rate monitor, and infrared temperature sensor; etc. as needed to collect data required by protocol.
- Change from baseline in electrocardiogram (ECG) parameters
- Change from baseline in clinical laboratory parameters (hematology, serum chemistry, coagulation and urinalysis)
Timepoint [1] 329900 0
Assessed during single ascending doses for Cohorts 1, 2, 3, 5 and 6 at the following timepoints.
- Adverse events (AEs) - AEs assessment will be performed throughout the study period
- Vital signs- On Day 1, Vital signs assessments are performed at 0.5 hour, 2 hours, 6 hours, 12 hours post dose administration. Followed by Vital signs being performed at Day 2, 3 , 4 and EOS/ETV.
- ECG- ECG is performed at 2 hours, 6 hours and 12 hours timepoints on Day 1. Followed by ECG being performed on Days 2, 3, 4 at 24 hours, 48 hours, 72 hours timepoints and at EOS/ETV.
- Lab Abnormalities (Hematology, serum chemistry and coagulation tests)- Day 1 at 6 hours, Day 2 at 24 hours, Day 3 at 48 hours timepoints and at EOS/ETV.
- Urinalysis- Day 1 at 6 hours , Days 2, 3, at 24 hours, 48 hours timepoints and at EOS/ETV.

Assessed during single ascending doses for Cohort 4 at the following timepoints.
- Adverse events (AEs) - AEs assessment will be performed throughout the study period
- Vital signs- Vital signs assessments are performed at 0.5 hour, 2 hours, 6 hours, 12 hours post dose administration on Day 1 (Fasting condition) and Day 4 (Fed condition). Followed by Vital sign assessments being performed on Days 2, 3 , 5, 6, 7 at 24 hours, 48 hours, 72 hours timepoints and at EOS/ETV.
- ECG- ECG is performed at 2 hours, 6 hours and 12 hours timepoints on Day 1 and Day 4. Followed by ECG being performed on Days 2, 3, 5, 6, 7 at timepoints of 24 hours, 48 hours, 72 hours and at EOS/ETV.
- Lab Abnormalities (Hematology, serum chemistry and coagulation tests)- Days 1 and 4 at 6 hours, Days 2, 3, 5, 6, 7 at 24 hours and 48 hours timepoints and at EOS/ETV.
- Urinalysis- Days 1 and 4 at 6 hours , Days 2, 3, 5, 6, 7 at 24 hours, 48 hours, 72 hours timepoints and at EOS/ETV.
Secondary outcome [1] 404199 0
To assess the pharmacokinetics (PK) of GSBR-1290 in plasma following administration of single oral doses in healthy adult volunteers.

The primary pharmacokinetic (PK) parameters of interest include Cmax, Tmax, t1/2, AUC0-last, AUC0-inf, Lambda-z, CL/F and Vz/F, Mean resident time (MRT0-t)
Timepoint [1] 404199 0
Cohorts 1, 2, 3, 5 & 6- Blood samples
Post dose PK samples are collected at 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 & at 12 hours. PK samples are collected on Days 2, 3 and 4 at 24, 48 and 72 hours respectively.
Secondary outcome [2] 404200 0
To assess the PK of GSBR-1290 in urine following administration of a single oral dose in healthy adult volunteers (Cohort 5 fasted condition). The parameters assessed for Urine PK endpoints include - Cumulative amount of unchanged drug excreted in urine (Ae) - Renal clearance (CLr)
Timepoint [2] 404200 0
Cohort 5 - Urine Samples Urine sample is collected -Day 1 to Day 3.
Secondary outcome [3] 404201 0
To assess the effect of food on the PK of GSBR-1290 following administration of a single oral dose in healthy adult volunteers under fasted and fed conditions (Cohort 4).

The primary pharmacokinetic (PK) parameters of interest include Cmax, Tmax, t1/2, AUC0-last, AUC0-inf, Lambda-z, CL/F and Vz/F
Timepoint [3] 404201 0
Cohort 4- Blood samples (Fasted and Fed conditions)
PK samples are collected on Days 1 and 4 at 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 & at 12 hours timepoints. PK samples are collected on Days 2, 3, 5, 6 and 7 at 24, 48 and 72 hours timepoints.

Eligibility
Key inclusion criteria
1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects
2. Adult males and females, 18 to 55 years of age (inclusive) at screening
3. Body mass index greater than or equal to 18.0 and less than or equal to 30.0 kg/m2, with a body weight (to 1 decimal place) greater than or equal to 45 kg at screening
4. Medically healthy without clinically significant abnormalities at the screening visit and prior to dosing at the timepoints indicated in the Schedules of Assessments (SoA)
5. Be nonsmokers (including tobacco, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration and have a negative breath test for cotinine at the screening visit and at check-in on Day -1.
6. Female volunteers must be of nonchildbearing potential i.e., surgically sterilized or postmenopausal or if of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method of contraception from signing the consent form until at least 30 days after the last dose of the study drug
7. Male volunteers must agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from signing the consent form until at least 90 days after the last dose of study drug
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant.
2. Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
3. Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
4. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia
5. Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate,
azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration.
6. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
7. Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants
8. Liver function tests outside the normal range for bilirubin (total, conjugated and unconjugated).
9. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B
surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
10. Presence or having sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
11. Estimated creatinine clearance (CrCl) less than 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN.
12. History of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]) within 12 weeks prior to the screening visit.
13. Positive drugs of abuse or alcohol breath test results at the screening visit or at check-in (Day -1).
14. Use of any prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 10 days or 5 half-lives of the medication.

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)
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

Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/02/2022
Actual
22/02/2022
Date of last participant enrolment
Anticipated
14/07/2022
Actual
21/06/2022
Date of last data collection
Anticipated
22/07/2022
Actual
23/08/2022
Sample size
Target
48
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21339 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 36229 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 310379 0
Commercial sector/Industry
Name [1] 310379 0
Gasherbrum Bio Pty Ltd. (Australian entity of ShouTi Inc)
Country [1] 310379 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Gasherbrum Bio Pty Ltd. (Australian entity of ShouTi Inc)
Address
Gasherbrum Bio Pty Ltd.
(Australian entity of ShouTi Inc)
c/o BDO Australia Ltd
Collins Square, Tower 4, Level 18
727 Collins Street
Docklands, VIC 3008, Australia
Country
Australia
Secondary sponsor category [1] 311521 0
Commercial sector/Industry
Name [1] 311521 0
Avance Clinical Pty Ltd
Address [1] 311521 0
Avance Clinical Pty Ltd
Level 1, 2 Ann Nelson Drive
Thebarton, SA 5031, Australia
Country [1] 311521 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310031 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 310031 0
Ethics committee country [1] 310031 0
Australia
Date submitted for ethics approval [1] 310031 0
13/12/2021
Approval date [1] 310031 0
02/02/2022
Ethics approval number [1] 310031 0
2021-12-1461

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116250 0
Dr Christopher Argent
Address 116250 0
Scientia Clinical Research
Bright Building, Level 5, Corner
High & Avoca Street, Randwick
NSW 2031, Australia
Country 116250 0
Australia
Phone 116250 0
+61 02 9382 5844
Fax 116250 0
Email 116250 0
[email protected]
Contact person for public queries
Name 116251 0
Christopher Argent
Address 116251 0
Scientia Clinical Research
Bright Building, Level 5, Corner
High & Avoca Street, Randwick
NSW 2031, Australia
Country 116251 0
Australia
Phone 116251 0
+61 02 9382 5844
Fax 116251 0
Email 116251 0
[email protected]
Contact person for scientific queries
Name 116252 0
Christopher Argent
Address 116252 0
Scientia Clinical Research
Bright Building, Level 5, Corner
High & Avoca Street, Randwick
NSW 2031, Australia
Country 116252 0
Australia
Phone 116252 0
+61 02 9382 5844
Fax 116252 0
Email 116252 0
[email protected]

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


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
No additional documents have been identified.