| Eligibility |
Single Dose Cohort-Inclusion Criteria:
1. Healthy male or female participants, aged 18 to 55 years (inclusive at the time of
informed consent);
2. Participants must be in good general health, with no significant medical history, have
no clinically significant abnormalities on physical examination at Screening and/or
before administration of study drug;
3. Participants must have a BMI greater than or equal to 20.0 kg/m2 and less than or
equal to 35.0 kg/m2 and weigh greater than or equal to 50 kg but less than or equal to
90 kg at Screening;
4. Stable body weight for at least three (3) months prior to Screening (i.e., <5%
change);
5. Participants must have A1c below 6.4%, FPG: 3.9 ~ 6.1 mmol/L (both inclusive) or
70~110 mg/dL (both inclusive). All other clinical laboratory values must be within
normal range as specified by the testing laboratory, unless deemed not clinically
significant by the Investigator or delegate;
6. Non-smoker and/or casual smoker who uses no more than 10 cigarettes (or equivalent
quantity of any other nicotine containing products e.g., cigars, chewing tobacco,
snuff, etc.) per week. Participants must abstain from smoking 5 days prior to
admission and throughout the confinement period, and test negative on Day -1 for urine
cotinine test. Participants must also abstain from smoking 72 hours prior to each
outpatient visit;
7. Participants must agree to abstain from alcohol intake from 48 hours prior to
admission and during the confinement period;
8. Women of childbearing potential (WOCBP) must be non-pregnant and must use an
acceptable, highly effective double contraception from Screening until study
completion, including the follow up period.
9. Males must not donate sperm for at least 90 days after the last dose of study drug;
10. Participants must have the ability and willingness to attend the necessary visits to
the CRU;
11. Participants must be willing and able to provide written informed consent after the
nature of the study has been explained and prior to the commencement of any study
procedures.
Single Dose Cohort-Exclusion Criteria:
1. Prior or ongoing medical conditions, medical history, physical findings, or laboratory
abnormality that, in the Investigator's (or delegate's) opinion, may require treatment
or render the participant unlikely to fully complete the study, or any condition that
presents undue risk from the IP or procedures or interfere with study assessments;
2. Confirmed diagnosis of diabetes mellitus type 1, type 2, or of any other forms at any
time, and/or occurrence of documented or suspected hypoglycaemic episodes within 12
months prior to Screening;
3. Personal or family history of medullary thyroid carcinoma or multiple endocrine
neoplasia type 2;
4. History of acute or chronic pancreatitis;
5. Participants must be willing not to undertake any strenuous exercise, including but
not limited to weightlifting (greater than 5 times per week) within 5 days prior to
first study drug administration and for the duration of the study (including the
follow-up period);
6. Participants must not start or having started participation in any medical (e.g.,
assisted by a clinical dietician or nutritionist) or non-medical (e.g., by a gym
coach) diet and/or exercise programme within 3 months prior to Screening and for the
duration of the study (including the follow-up period);
7. Use and/or planned use of any approved or unapproved weight-lowering medication(s)
(including but not limited to orlistat, sibutramine, rimonabant, phentermine, or
liraglutide) and/or medical device(s) within 3 months prior to Screening and for the
duration of the study (including the follow-up period);
8. Previous history of any major gastrointestinal (including hepatobiliary and/or
pancreatic) surgeries, including but not limited to sleeve, subtotal, or total
gastrectomy, gastrojejunostomy, gastroduodenectomy, gastroduodenostomy, jejunectomy,
ileectomy (proto)colectomy, hepatectomy, and pancreatectomy (except for appendectomy
or cholecystectomy) and planned performance of one or more of the above mentioned for
the duration of the study (including the follow-up period);
9. History of cerebral stroke (including but not limited to cerebral
infarction/hemorrhage) within 12 months prior to Screening;
10. History of acute coronary syndrome (angina pectoris/myocardial infarction) and any
other major cardiac conditions (including but not limited to myocarditis, cardiac
insufficiency/failure, and any clinically significant arrythmia[s]) within 12 months
prior to Screening;
11. Systolic blood pressure (BP) greater than 140 mmHg and/or less than 90 mmHg and/or
diastolic BP greater than 90 mmHg and/or less than 40 mmHg and/or pulse rate greater
100 bpm and/or less than 40 bpm at Screening with one repeat allowed per by the
Investigator or delegate at Screening and/or on Admission
12. Any clinically significant arrhythmia(s) at Screening ECG; specifically, the
participant's corrected QT interval (QTcF) (Fridericia's correction) is greater than
450 ms at Screening and on Day -1. An out-of-range or abnormal ECG may be repeated
during Screening. On admission, three ECGs should be recorded consecutively, and the
Investigator must evaluate the triplicate ECG. If the participant's QTcF is greater
than 450 ms on at least two ECGs, the participant must be excluded;
13. Any medically uncontrolled respiratory disease(s) and/or condition(s), including but
not limited to severe current asthma, chronic obstructive pulmonary disease, and
obstructive sleep apnoea syndrome;
14. Fever (body temperature greater than 38°C) or symptomatic viral or bacterial infection
within 2 weeks prior to Screening;
15. Clinically significant gastrointestinal disease(s), including but not limited to
inflammatory bowel disease, irritable bowel syndrome, celiac disease, dyspepsia,
apparent diabetic gastroparesis, and diabetic diarrhoea;
16. With alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or alkaline
phosphatase (ALP) greater than 1.5 × upper limit of normal (ULN) at Screening. Repeat
testing at Screening is acceptable for out of range values following approval by the
Investigator or delegate;
17. With a confirmed creatinine clearance (CLcr) using the Cockcroft-Gault equation below
90 mL/min. Repeat testing at Screening is acceptable for out of range values following
approval by the Investigator or delegate;
18. History of clinically significant endocrine condition(s), including but not limited to
hyper/hypothyroidism and/or hyper/hypoadrenalism;
19. History of primary or recurrent malignancy, except for non-melanoma skin cancer
excised more than 2 years prior to Screening and/or cervical intraepithelial neoplasia
having been successfully cured more than 5 years prior to Screening;
20. With clinically significant haematologic abnormalities, including but not limited to
haemoglobin above 180 g/L and/or below 110 g/L, white blood cell count (WBC) above
10.5×10^9/L and/or below 3.5×10^9/L, absolute neutrophil count above 7.0×10^9/L and/or
below 2.0×10^9/L, and/or platelet count above 300×10^9/L and/or below 130×10^9/L.
Repeat testing at Screening is acceptable for out of range values following approval
by the Investigator or delegate;
21. With any other clinically significant laboratory abnormalities in clinical
biochemistry, coagulation function, and/or urinalysis. Repeat testing at Screening is
acceptable for out of range values following approval by the Investigator or delegate;
22. With positive test result(s) for hepatitis C virus (HCV) antibody, hepatitis B surface
antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at Screening;
23. History of life-threatening infection (e.g. meningitis) and/or any major infections
requiring parental antimicrobials within 6 months prior to Screening;
24. Regular alcohol consumption (by self-declaration) defined as greater than 21 alcohol
units per week (where 1 unit = 284-mL of beer, 25-mL of 40% spirit or a 125-mL glass
of wine). Participant is unwilling to abstain from alcohol beginning 48 hours prior to
admission to the CRU and during the confinement period;
25. With a history of substance abuse or dependency in the last 12 months, or a history of
recreational intravenous drug use over the last 5 years (by self-declaration);with a
positive toxicology screening panel (urine test including qualitative identification
of barbiturates, tetrahydrocannabinol [THC], amphetamines, methamphetamines,
methylenedioxy-methamphetamine [MDMA], phencyclidine, benzodiazepines, opiates and
cocaine), or alcohol breath test;
26. History of severe allergic or anaphylactic reactions;
27. Known or suspected intolerance or hypersensitivity to the IP, close related compounds,
or any of the stated ingredients;
28. Blood donation or significant blood loss (greater than or equal to 400 mL) within 60
days prior to the first study drug administration;
29. Plasma donation within 7 days prior to the first study drug administration;
30. Being pregnant or lactating at Screening or planning to become pregnant (self or
partner) at any time during the study and for at least 3 months after the last dose of
study drug;
31. Use of any IP or investigational medical device within 30 days prior to Screening, or
5 half lives of the product (whichever is the longest) or participation in more than
four investigational drug studies within 1 year prior to Screening;
32. Previous treatment with glucagon-like peptide 1 (GLP-1) agonists within the last 3
months;
33. Use of any prescription drug(s) and medical device(s) (other than hormonal
contraception:
OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring, or an
IUD) within 2 weeks prior to the first study drug dosing or use of any over
the-counter (OTC) medication, herbal remedies, supplements or vitamins within 1 week
prior to the first study drug dosing and during the course of the study without prior
approval of the Investigator and MM. Use of simple analgesic(s) (e.g., paracetamol, a
nonsteroidal anti-inflammatory drug [NSAID]) may be permitted at the discretion of the
Investigator;
34. Present comedication with drugs known to interfere with glucose metabolism, such as
systemic corticosteroids, non-selective beta-blockers, and monoamine oxidase
inhibitors;
35. Presence of any underlying physical and/or psychological medical condition that, in
the opinion of the Investigator, would make it unlikely that the subject will comply
with the protocol or complete the study per protocol.
Repeat Dose Cohort - Inclusion Criteria
To be eligible for this study, participants must meet all of the following additional
inclusion criteria:
1. Participants must have a Body Mass Index (BMI) =24.0 kg/m2 and =34.0 kg/m2 and a Body
weight =70 kg;
2. Participants must be willing to test and document glucose at home using a glucometer;
Repeat Dose Cohort - Exclusion Criteria:
A participant who meets any of the following additional exclusion criteria must be excluded
from the study:
1. Obesity induced by endocrine disorders (e.g., Cushing Syndrome);
2. Any clinical laboratory values deviating from or outside the laboratory reference
range unless considered not to be clinically significant by the Investigator or
delegate;
3. History of thyroid tumors of family history of thyroid tumors.
4. Hemoglobin, white cell count, neutrophil count, and platelet count must fall within
the laboratory's normal ranges. Any other hematological parameters outside the normal
range may be acceptable if clinically insignificant and at the Investigator's
discretion. Repeat testing at Screening is acceptable following approval by the
Investigator or delegate;
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