A Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ZYD1, Following Subcutaneous Administration in Healthy Volunteers

Study Overview
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Brief Summary
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ZYD1 is a novel GLP-1 receptor agonist. The ZYD1 exhibits increased stability to proteolytic cleavage, especially against dipeptidyl peptidase-4 (DPP-IV). ZYD1 is a potent antidiabetic agent without gastrointestinal side-effects. A first in human (FIH) Phase I study intends to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ZYD1 in normal healthy adult volunteers.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ZYD1, a Selective Glucagon-like Peptide (GLP) 1 Agonist, Following Subcutaneous Administration in Healthy Volunteers.

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: ZYD1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-45 years Mentally, physically, and legally eligible to give informed consent Male and female volunteers weighing between 50-75 kg and 45-75 kg respectively Ability to communicate effectively with the study personnel Willingness to adhere to the protocol requirements For gender effect study, only females with history of sterility or at least 1 year menopause or use of long acting nonhormonal contraceptive measures (e.g., intrauterine device) will be recruited. Exclusion Criteria: Presence or history of hypersensitivity to any of the active or inactive ingredients of ZYD1 formulation Presence or history of pancreatitis at any time (Serum Amylase/Serum Lipase more than upper normal limit (UNL)) Presence or history of severe gastrointestinal disease in the last 6 months Presence or history of renal insufficiency at any time (serum creatinine above the upper limit of the reference range) Active liver disease and/or liver transaminases greater than 1.5 X UNL Subject with personal or family history of medullary thyroid cancer Subject with personal or family history of multiple endocrine neoplasia syndrome type 2 Subject with serum calcitonin >50 ng/L History or presence of other systemic disorders or diseases (e.g., respiratory, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or any other body system involvement) Abnormal bleeding time (BT), clotting time (CT), prothrombin time (PT), and activated partial prothrombin time (APTT) tests on the day of check in History or presence of any medication in the last 14 days including any medication known to interact with the Cytochrome P (CYP) 450 system History or presence of significant alcoholism or drug abuse within the past 1 year History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco products (more than 10 times per day) Difficulty with donating blood Systolic blood pressure more than 140 mmHg and less than 100 mmHg and diastolic blood pressure more than 90 mmHg and less than 60 mmHg Pulse rate less than 60/minute and more than 100/minute Any clinically significant abnormal X-ray or laboratory findings during screening History or presence of any clinically significant electrocardiogram (ECG) abnormalities during screening Major illness and/or major surgery in last 3 months Volunteers who have participated in any drug research study other than the present trial within past 3 months Volunteers who have donated one unit (350 ml) of blood in the past 3 months For gender effect study, female volunteers with following criteria will not be recruited: History of pregnancy or lactation in the past 3 months Fertile female volunteers not protected against pregnancy by adequate long-term anti-fertility device or history of less than 1 year of menopause Using hormonal contraceptives Using hormone replacement therapy Unable to give assurance for protection against pregnancy for 3 months after the participation in this trial Positive urine pregnancy test on the day of check-in

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZYD1<br>Tablet ZYD1 5 to 50 mg subcutaneously Once a day (OD) or BID depending upon the pharmacokinetic profile obtained in Plan I (Single dose study) | Drug: ZYD1<br>* Plan I - Tablet ZYD1 - 0.5, 1 , 2, 5, 10, 25 and 50 mg subcutaneously OD after overnight fasting. Plan II - Tablet ZYD1 - 0.5, 1 , 2, 5, 10 and 25 mg subcutaneously OD after overnight fasting. Plan III - Tablet ZYD1 2/5 mg subcutaneously OD after overnight fasting depending on results of Plan I.<br>* Other names: Selective GLP-1 agonist;|
| Placebo Comparator: Placebo<br>Tablet Placebo 5 to 50 mg subcutaneously OD or BID depending upon the pharmacokinetic profile obtained in Plan I (Single dose study) | Drug: Placebo<br>* Plan I - Tablet Placebo - 0.5, 1 , 2, 5, 10, 25 and 50 mg subcutaneously OD after overnight fasting. Plan II - Tablet Placebo - 0.5, 1 , 2, 5, 10 and 25 mg subcutaneously OD after overnight fasting. Plan III - Tablet Placebo 2/5 mg subcutaneously OD after overnight fasting depending on results of Plan I.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate Safety and tolerability of ZYD1 | The safety and tolerability shall be evaluated using physical examinations, standard laboratory tests (hematology, biochemistry and urine examination), and electrocardiogram (ECG). Spontaneously reported and solicited adverse events will also be used for safety parameters. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) and Pharmacodynamic (PD) effect after single and multiple subcutaneous dose administrations in healthy adult male volunteers Gender effect study. | PK parameters evaluated for Plan I and Plan III: Cmax, Tmax, Area Under Curve (AUC)0-t, AUC 0-inf, T1/2, z, Clearance(CL), Volume of distribution (Vd) Plan II: Cmin, Tmin, Cavg, % Fluctuation, Accumulation Index, Clss, Cmax, Vd or Vss For urine data (Plans I, II, and III): Amount recovered, % recovered The following PD parameters (Plan I-III) will be evaluated: Plasma glucose, Serum insulin, C-Peptide, Glucagon Gender effects: PK and PD effect in female volunteers at preselected single dose will be compared with the results of single-dose study in male volunteers. | 1. For Plan I and III - Pre-dose (before dosing), 0.5, 1, 2, 3, 4, 6 ,8, 10, 12, 24, 48, 72 and 120 hrs post dose 2. Plan II - Day 01 - Pre-dose, 1, 2, 3, 4 and 8 hours following first dosing. Day 02 to 06 - Pre-dose of each . Day 07 - Pre-dose, 1, 2, 3, | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Selective GLP-1 agonist