A Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570

Study Overview
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Brief Summary
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The trial is a Phase 1, single-centre, randomised and double-blind within cohorts, placebo-controlled, sequential multiple ascending dose trial including three cohorts in a semi-parallel design in overweight and obese but otherwise healthy subjects, randomised to ZP7570 or placebo within each cohort where the observational period is 18 weeks. All subjects will be dosed for 13 weeks with ascending weekly doses of ZP7570 at dose levels with corresponding volume of placebo.

Detailed Description
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ZP7570 is a dual GLP-1R/GLP-2R agonist in clinical development for weight management. The overall purpose of this trial is to evaluate the safety and tolerability when applying dose titration of ascending doses of ZP7570 and at steady state. The trial is a Phase 1, single-centre, randomised and double-blind within cohorts, placebo-controlled, sequential multiple ascending dose trial including three cohorts in a semi-parallel design in overweight and obese but otherwise healthy subjects, randomised to ZP7570 or placebo. All subjects will be dosed with ascending weekly doses of ZP7570 with corresponding volume of placebo. After informed consent has been obtained, eligibility of the subjects will be assessed during a screening Visit (V1). Additional tests to assess safety and PK and PD will take place during in-house visits and ambulatory visits.

Official Title
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A Randomised, Multiple Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570 Administered in Subjects With Overweight or Obesity

Conditions
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Safety and Tolerability

Intervention / Treatment
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* Drug: ZP7570
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 64 years, both inclusive. Body Mass Index (BMI) between 27.0 and 39.9 kg/m^2, both inclusive. In overall good health according to age (medical history, physical and neurological examination, vital signs, and laboratory assessments), as judged by the investigator at screening. Exclusion Criteria: History of gastrointestinal (GI) diseases including functional complaints that could interfere with the pharmacokinetics of the IMP or auxiliary medicinal product (acetaminophen) of the trial. Any relevant abnormal renal parameters in the following ranges: Serum creatinine above UNL+10% or normalised estimated glomerular filtration rate (eGFR) below 60.0 l/min/1.73m2, as defined by CKD-EPI.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: The trial is a single-centre, randomised and double-blind within cohorts, placebo-controlled, sequential multiple ascending dose trial including three cohorts in a semi-parallel design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ZP7570<br>ZP7570 for subcutaneous once-weekly injection. | Drug: ZP7570<br>* 13 once-weekly subcutaneous injections<br>* Other names: GLP-1/GLP-2 agonist;|
| Placebo Comparator: Placebo<br>Placebo for subcutaneous once-weekly injection. Corresponding volume matching active treatment | Drug: Placebo<br>* 13 once-weekly subcutaneous injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (TEAEs) | Incidence of treatment emergent adverse events (TEAEs) from first dose (Day 1) to end of trial (Day 127) | Day 1 to Day 127 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics endpoints related to ZP7570 exposure | Pharmacokinetics: Area under the plasma concentration curve from baseline (Day 1, predose) to 18 weeks (Day 127) . | Area under the drug concentration curve from baseline to 18 weeks (Day 1 predose to Day 127) | 
| Pharmacokinetics endpoints related to ZP7570 exposure | Pharmacokinetics - Maximum plasma concentration (peak) from baseline (Day 1, predose) to 18 weeks (Day 127). | Maximum drug concentration (Cmax) from baseline to 18 weeks (Day 1, predose to Day 127) | 
| Pharmacokinetics endpoints related to ZP7570 exposure | Pharmacokinetics - Time to maximum plasma concentration (Tmax) from baseline (Day 1, predose) to 18 weeks (Day 127). | Time to maximum plasma concentration from baseline to 18 weeks (Day 1, predose to Day 127) | 
| Pharmacokinetics endpoints related to ZP7570 exposure | Pharmacokinetics - Elimination rate constant (λz) from baseline (Day 1, predose) to 18 weeks (Day 127). | Elimination rate constant from baseline to 18 weeks (Day 1, predose to Day 127) | 
| Pharmacokinetics endpoints related to ZP7570 exposure | Pharmacokinetics - Elimination half-life (t1/2) from baseline (Day 1, predose) to 18 weeks (Day 127). | Elimination half-life from baseline to 18 weeks (Day 1, predose to Day 127) | 
| Pharmacokinetics endpoints related to ZP7570 exposure | Pharmacokinetics - Apparent volume of distribution (Vz/f) during the terminal phase from baseline (Day 1, predose) to 18 weeks (Day 127). | Apparent volume of distribution from baseline to 18 weeks (Day 1, predose to Day 127)) | 
| Pharmacokinetics endpoints related to ZP7570 exposure | Pharmacokinetics - Apparent total clearance of the drug from plasma (Cl/f) from baseline (Day 1, predose) to 18 weeks (Day 127). | Apparent total clearance of the drug from plasma from baseline to 18 weeks (Day 1, predose to Day 127) | 
| Pharmacokinetics endpoints related to ZP7570 exposure | Pharmacokinetics - Trough concentration measured predose (Ctrough) from baseline (Day 1, predose) to 18 weeks (Day 127). | Trough concentration measured from baseline to 18 weeks (Day 1, predose to Day 127) | 
| Absolute change in body weight | Absolute change in body weight in kilogram (kg) from baseline (Day 1) to end of treatment (Day 92) | Day 1 and Day 92 | 
| Percent change in body weight | Percent change in body weight in percent (%) from baseline (Day 1) to end of treatment (Day 92) | Day 1 and Day 92 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GLP-1/GLP-2 agonist, overweight, obesity