Diabetes Mellitus, Type 2
Conditions
Brief summary
Single ascending dose first time in human study for GZR18 in healthy subjects
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
Interventions
DRUGGZR-18
As previously described in Arms
OTHERPlacebo
Placebo will be dosed in an identical manner to active study drug.
Sponsors
Gan and Lee Pharmaceuticals, USA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Enrollment of up to 56 subjects in up to 7 cohorts may occur. Randomization is 3:1 (active drug:placebo) across all cohorts. Within each cohort, 6 subjects will be randomized to receive GZR18, and 2 subjects will be randomized to receive placebo.
Intervention model description
This is a double-blinded, randomized, placebo-controlled, sequential, dose-escalating, single-dose study.
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicity | Up to 31 days | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration | Up to 720 hours | Cmax |
| Glycosylated Hemoglobin | Up to 720 hours | HbA1c |
Countries
United States
Outcome results
None listed