A Single Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, single ascending dose trial in healthy subjects, randomized to ZP7570 or placebo within each cohort.

Detailed Description
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Sixty-four subjects are planned to be studied in eight cohorts in this first-in human trial. Eight subjects will be allocated to the to eight dose levels. The entire observation period comprise 28 days starting with a 96 hours in-house stay, where discharge is planned for Day 5, followed by five outpatient visits and an End of Trial Visit at Day 28. A blinded evaluation of each cohort will be performed by a Trial Safety Group to determine whether the trial will progress to the next dose level based on the stopping rules specified in protocol.

Official Title
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A First in Human, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Subcutaneous Dose of ZP7570 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dual GLP-1/GLP-2 Receptor agonists


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subject aged between 18 and 55 years, both inclusive. Body Mass Index (BMI) between 18.5 and 28.0 kg/m^2, both inclusive Body weight of at least 60 kg. Heart rate after 5 minutes rest in supine position inside the range of 50-90 beats/min at screening Exclusion Criteria: Any history of a disorder which in the investigator's opinion might jeopardize subjects safety, evaluation of results or compliance with the protocol. History of gallbladder disease or cholecystectomy. History of major depressive disorder or a Patient Health Questionnaire (PHQ-9) > 9 completed at screening, or a history of other severe psychiatric disorders (e.g. schizophrenia or bipolar disorder). Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to screening. Clinically significant abnormal standard 12-lead ECG after 5 min resting in supine position at screening, including a QTcF > 450 ms (males) or QTcF > 470 ms (females), PR ≥ 220 ms and QRS ≥ 110 ms as evaluated by the investigator. History of severe hypersensitivity to medicines or foods or history of severe medicinal/food induced anaphylactic reaction or contraindication to the use of Indocyanine Green (e.g. hypersensitivity to iodine). Any clinically significant abnormal hematology, biochemistry, or urinalysis screening tests, as judged by the investigator. TSH values outside of normal reference ranges of safety laboratory Estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2, as defined by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Known or suspected hypersensitivity to IMP(s) or related products. Systolic blood pressure < 90 mmHg or >139 mmHg and/or diastolic blood pressure < 50 mmHg or > 89 mmHg (one repeat test will be acceptable in case of suspected white-coat hypertension). Symptoms of arterial hypotension Women of childbearing potential who are not using a highly effective contraceptive method Men with non-pregnant partner(s) of childbearing potential not willing to use male contraception (condom) in addition to a highly effective contraceptive method until 28 days after dosing Men with pregnant partner not willing to use male contraception (condom) until 28 days after dosing, in order to avoid exposure of the embryo/fetus to seminal fluid

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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
Interventional Model Description: A randomized, double-blind, placebo-controlled, single ascending dose trial in healthy subjects, randomized to ZP7570 or placebo
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ZP7570<br>Single subcutaneous injection | Drug: Dual GLP-1/GLP-2 Receptor agonists<br>* Eight ascending doses of ZP7570<br>* Other names: ZP7570;|
| Placebo Comparator: Placebo<br>Single subcutaneous injection | Drug: Dual GLP-1/GLP-2 Receptor agonists<br>* Eight ascending doses of ZP7570<br>* Other names: ZP7570;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Incidence of adverse events (AEs) | The incidence, type and severity of adverse events (AEs) | From time zero to 28 days after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics - Area under the plasma concentration-time curve trough | AUCτ, Area under the plasma concentration-time curve (AUC) from zero up to trough concentration. | From time zero up to day 28 | 
| Pharmacokinetics - Area under the plasma concentration-time curve infinity | AUCinf, Area under the plasma concentration-time curve (AUC) from zero up to last concentration. | From time zero up to day 28 | 
| Pharmacokinetics - Area under the plasma concentration-time curve last | AUClast, Area under the plasma concentration-time curve (AUC) from zero up to last concentration | From time zero up to day 28 | 
| Pharmacokinetics - Maximum plasma concentration | Measured maximum plasma drug concentration after dosing, Cmax | From time zero to 28 days after dosing | 
| Pharmacokinetics - Time to maximum plasma concentration (Tmax) | Sampling time until reaching Cmax, Tmax | From time zero to 28 days after dosing | 
| Pharmacokinetics - Half-life , t½ | Half-life of ZP7570, t½ | From time zero to 28 days after dosing | 
| Pharmacokinetics - Volume of distribution | Apparent volume of distribution of ZP7570, Vz/f | From time zero to 28 days after dosing | 
| Pharmacokinetics - Mean residence time | Mean residence time, MRT | From time zero to 28 days after dosing | 
| Pharmacokinetics - Body clearance | Total body clearance, CL/f | From time zero to 28 days after dosing | 
| Pharmacokinetics - Elimination rate constant | Elimination rate constant, λz | From time zero to 28 days after dosing | 
| Pharmacodynamics - Plasma glucose levels | Plasma glucose levels included with the acetaminophen at specific timepoints relative to a Mixed Test Meal | Time Frame: 0-240 minutes | 
| Pharmacodynamics - Insulin concentrations | Insulin concentrations included with the acetaminophen at specific timepoints relative to a Mixed Test Meal | Time Frame: 0-240 minutes | 
| Pharmacodynamics - Plasma acetaminophen concentration-time curves | Plasma acetaminophen concentration-time curves following ingestion of acetaminophen | Time Frame: 0-240 minutes | 
| Pharmacodynamics - Maximum acetaminophen concentration | Change from baseline acetaminophen to maximum acetaminophen | Time Frame: 0-240 minutes | 
| Pharmacodynamics - Time maximum acetaminophen concentration | Time to maximum change in acetaminophen measure from baseline, Tmax | Time Frame: 0-240 minutes | 
| Safety - Safety lab, haematology | Changes in haematology parameters: Haematocrit, Haemoglobin, Erythrocytes, MCV, MCH, MCHC, platelets, Leucocytes, Neutrophile granulocytes (total count and relative), Lymphocytes (total count and relative), Monocytes (total count and relative), Eosinophile granulocytes (total count and relative), Basophile granulocytes (total count and relative) | From time zero to 28 days after dosing | 
| Safety - Safety lab, clinical chemistry | Changes in clinical chemistry parameters: Sodium, Potassium, Calcium, Creatinine, Urea, AST, ALT, gamma-GT, Uric acid, Total protein, Albumin, Total bilirubin, Creatine kinase, Alkaline phosphatase, LDH, Total cholesterol, LDL, HDL, Amylase, Triglycerides, Lipase | From time zero to 28 days after dosing | 
| Safety - Safety lab, urinalysis | Changes in urinalysis: Protein, Glucose Erythrocytes, Leucocytes, pH, ketones | From time zero to 28 days after dosing | 
| Safety - Vital signs, blood pressure | Changes in vital signs, blood pressure (in mmHG) | From time zero to 28 days after dosing | 
| Safety - Vital signs, pulse | Changes in pulse (beats per minute) | From time zero to 28 days after dosing | 
| Safety - Physical examination | Changes in physical examination of body sections (head, chest and heart, abdomen, skin and mucosae, musculoskeletal system, nervous system, lymph node) | From time zero to 28 days after dosing | 
| Safety - ECG | Occurrence of ECG findings, Changes in ECG parameters (in ms). ECG components: Heart rate, PR, QRS, QT and QTcF. | From time zero to 28 days after dosing | 
| Safety - Occurrence of Injection site reactions | Occurrence of injection site reactions | From time zero to 28 days after dosing | 
| Safety - Immunogenicity: Occurrence of anti-drug antibodies | Occurrence of anti-drug antibodies | From time zero to 28 days after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dual GLP-1R/GLP-2 Receptor agonist