Single, Ascending Dose, First Time in Human Study for GZR18 in Healthy Subjects

Study Overview
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Brief Summary
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Single ascending dose first time in human study for GZR18 in healthy subjects

Detailed Description
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A double-blind, randomized, placebo-controlled, sequential, single, ascending dose study to evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic parameters of subcutaneous injections of GZR18 in healthy subjects

Official Title
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A Double-blind, Randomized, Placebo-controlled, Sequential, Single, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Parameters of Subcutaneous Injections of GZR18 in Healthy Subjects

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: GZR-18
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign and date informed consent prior to any study-related activities being performed Be considered healthy in the opinion of the PI or qualified designee and have no clinically significant abnormal laboratory values at screening Male Aged 18 to 60 years, inclusive, at the time of signing the informed consent. Note: if the study is to be conducted at a clinical site located in Lincoln, Nebraska, the lower age limit will be 19 years of age Have a BMI between 20.0 to 35.0 kg/m2, inclusive, at Screening or check-in prior to dosing Have a normal renal function as defined by estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73m2 at Screening or check-in prior to dosing Be able to understand and comply with protocol requirements, instructions, and any protocol-stated restrictions Exclusion criteria: The Investigator or qualified designee considers the subject unfit for the study, based on medical interview, physical examination, or laboratory results. Individuals must be free from clinically significant illness or disease, as determined by the PI or qualified designee, with no clinically significant abnormality identified on the medical or laboratory evaluations, including 12-lead ECG Positive hepatitis-B surface antigen, positive hepatitis-C, or positive HIV test History of cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to screening Personal or family history of medullary cell carcinoma or multiple endocrine neoplasia syndrome type 2 History of inadequately controlled thyroid disease, as reflected by an abnormal thyroid stimulating hormone test or free T4 History of gastrointestinal disease that could affect fat or bile acid ab-sorption, including inflammatory bowel disease, chronic diarrhea, Crohn's disease, or malabsorption syndromes within the past year. Note: Subjects with a cholecystectomy more than 1 year prior to screening can be considered for inclusion in the study History of gastrointestinal surgical intervention for obesity History of chronic or acute pancreatitis History of significant drug or other allergy or hypersensitivity that, in the opinion of the Investigator or qualified designee, contraindicates the subject's participation in the study History of alcohol abuse, defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units. One unit is defined as equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine Unwilling to abstain from alcohol from 24 hours prior to the start of dosing until discharge from the clinic Smoked or used tobacco- or nicotine-containing products within the previous 6 months prior to Screening Treatment with an investigational drug or participated in any other interventional clinical study during the previous 30 days or within 5 half-lives after the last dose of the investigational drug, whichever is longer. Note: 30-day/5-half-life washout is defined as last dose of investigational drug in the previous study until the first screening visit in the current study Unwilling to refrain from the use of illicit drugs and unwilling to ad-here to other protocol-stated restrictions while participating in the study Unwilling to abstain from caffeine- or xanthine-containing products from 24 hours prior to dosing until discharge from the clinic A positive drug and alcohol screen at screening or check-in prior to dosing A positive pre-study urine cotinine screen indicating use of tobacco/nicotine-containing products at Screening or check-in prior to dosing Use of prescription or non-prescription drugs, vitamins, or dietary/herbal supplements within 1 week prior to the dosing of study drug through the final follow-up visit Donated 500 mL or greater of blood within 56 days prior to dosing or plans on donating blood in the 30 days following completion of the study Have any condition that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of the data

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a double-blinded, randomized, placebo-controlled, sequential, dose-escalating, single-dose study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug:GZR-18 administered via subcutaneous injection<br>For Assigned Interventions: GZR-18 administered once via subcutaneous injection at doses of 1.0 ug/kg, 5.0 ug/kg, 10.0 ug/kg, 20.0 ug/kg, 30.0 ug/kg, 40.0 ug/kg & 50.0 ug/kg | Drug: GZR-18<br>* As previously described in Arms<br>|
| Placebo Comparator: Placebo control<br>Commercially obtained sterile, normal saline for injection will be used as the matching placebo. Placebo will be dosed in an identical manner to active study drug. The volume of placebo will be calculated according to body weight using active drug dose for volume calculation in order to maintain the study blind. | Other: Placebo<br>* Placebo will be dosed in an identical manner to active study drug.<br>* Other names: Placebo Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity | The primary outcome for this study is Dose Limiting Toxicity, which is the composite of any SAE, any pancreatitis(as measured by amylase) or renal dysfunction (as measured by serum creatinine) | Up to 31 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration | Cmax | Up to 720 hours | 
| Glycosylated Hemoglobin | HbA1c | Up to 720 hours |