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

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

Single ascending dose first time in human study for GZR18 in healthy subjects

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: GZR-18; Other: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gary Furda; Phone Number: +1 267 378 5468; Email: Gary.Furda@ganlee.us
• Study Contact Backup: Name: Kimberly Lazaroff, MSN; Phone Number: (512) 827-1620; Email: Kimberly.Lazaroff@ganlee.us

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Sign and date informed consent prior to any study-related activities being performed
2. Be considered healthy in the opinion of the PI or qualified designee and have no clinically significant abnormal laboratory values at screening
3. Male
4. 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
5. Have a BMI between 20.0 to 35.0 kg/m2, inclusive, at Screening or check-in prior to dosing
6. 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

7. Be able to understand and comply with protocol requirements, instructions, and any protocol-stated restrictions

   Exclusion criteria:

8. 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
9. Positive hepatitis-B surface antigen, positive hepatitis-C, or positive HIV test
10. History of cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to screening
11. Personal or family history of medullary cell carcinoma or multiple endocrine neoplasia syndrome type 2
12. History of inadequately controlled thyroid disease, as reflected by an abnormal thyroid stimulating hormone test or free T4
13. 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
14. History of gastrointestinal surgical intervention for obesity
15. History of chronic or acute pancreatitis
16. 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
17. 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
18. Unwilling to abstain from alcohol from 24 hours prior to the start of dosing until discharge from the clinic
19. Smoked or used tobacco- or nicotine-containing products within the previous 6 months prior to Screening
20. 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
21. Unwilling to refrain from the use of illicit drugs and unwilling to ad-here to other protocol-stated restrictions while participating in the study
22. Unwilling to abstain from caffeine- or xanthine-containing products from 24 hours prior to dosing until discharge from the clinic
23. A positive drug and alcohol screen at screening or check-in prior to dosing
24. A positive pre-study urine cotinine screen indicating use of tobacco/nicotine-containing products at Screening or check-in prior to dosing
25. 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
26. 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
27. Have any condition that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of the data

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug:GZR-18 administered via subcutaneous injection; 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; As previously described in Arms
Placebo Comparator: Placebo control; 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; Placebo will be dosed in an identical manner to active study drug.; Other Names: Placebo Control

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gan and Lee Pharmaceuticals, USA
• Investigators: Study Director: Kimberly Lazaroff, MSN, Gan and Lee Pharmaceuticals, USA Corp

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2022
• Primary Completion (Actual): February 9, 2023
• Study Completion (Actual): March 9, 2023

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: GL-GLP-1012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No