A Single Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570
- Conditions
- Healthy
- Interventions
- Drug: Dual GLP-1/GLP-2 Receptor agonists
- Registration Number
- NCT03994549
- Lead Sponsor
- Zealand Pharma
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ZP7570 Dual GLP-1/GLP-2 Receptor agonists Single subcutaneous injection Placebo Dual GLP-1/GLP-2 Receptor agonists Single subcutaneous injection
- Primary Outcome Measures
Name Time Method Safety - Incidence of adverse events (AEs) From time zero to 28 days after dosing The incidence, type and severity of adverse events (AEs)
- Secondary Outcome Measures
Name Time Method Pharmacokinetics - Area under the plasma concentration-time curve trough From time zero up to day 28 AUCτ, Area under the plasma concentration-time curve (AUC) from zero up to trough concentration.
Pharmacokinetics - Area under the plasma concentration-time curve infinity From time zero up to day 28 AUCinf, Area under the plasma concentration-time curve (AUC) from zero up to last concentration.
Pharmacokinetics - Area under the plasma concentration-time curve last From time zero up to day 28 AUClast, Area under the plasma concentration-time curve (AUC) from zero up to last concentration
Pharmacokinetics - Maximum plasma concentration From time zero to 28 days after dosing Measured maximum plasma drug concentration after dosing, Cmax
Pharmacokinetics - Time to maximum plasma concentration (Tmax) From time zero to 28 days after dosing Sampling time until reaching Cmax, Tmax
Pharmacokinetics - Half-life , t½ From time zero to 28 days after dosing Half-life of ZP7570, t½
Pharmacokinetics - Volume of distribution From time zero to 28 days after dosing Apparent volume of distribution of ZP7570, Vz/f
Pharmacokinetics - Mean residence time From time zero to 28 days after dosing Mean residence time, MRT
Pharmacokinetics - Body clearance From time zero to 28 days after dosing Total body clearance, CL/f
Pharmacokinetics - Elimination rate constant From time zero to 28 days after dosing Elimination rate constant, λz
Pharmacodynamics - Plasma glucose levels Time Frame: 0-240 minutes Plasma glucose levels included with the acetaminophen at specific timepoints relative to a Mixed Test Meal
Pharmacodynamics - Insulin concentrations Time Frame: 0-240 minutes Insulin concentrations included with the acetaminophen at specific timepoints relative to a Mixed Test Meal
Pharmacodynamics - Plasma acetaminophen concentration-time curves Time Frame: 0-240 minutes Plasma acetaminophen concentration-time curves following ingestion of acetaminophen
Pharmacodynamics - Maximum acetaminophen concentration Time Frame: 0-240 minutes Change from baseline acetaminophen to maximum acetaminophen
Pharmacodynamics - Time maximum acetaminophen concentration Time Frame: 0-240 minutes Time to maximum change in acetaminophen measure from baseline, Tmax
Safety - Safety lab, haematology From time zero to 28 days after dosing 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)
Safety - Safety lab, clinical chemistry From time zero to 28 days after dosing 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
Safety - Safety lab, urinalysis From time zero to 28 days after dosing Changes in urinalysis: Protein, Glucose Erythrocytes, Leucocytes, pH, ketones
Safety - Vital signs, blood pressure From time zero to 28 days after dosing Changes in vital signs, blood pressure (in mmHG)
Safety - Vital signs, pulse From time zero to 28 days after dosing Changes in pulse (beats per minute)
Safety - Physical examination From time zero to 28 days after dosing Changes in physical examination of body sections (head, chest and heart, abdomen, skin and mucosae, musculoskeletal system, nervous system, lymph node)
Safety - ECG From time zero to 28 days after dosing Occurrence of ECG findings, Changes in ECG parameters (in ms). ECG components: Heart rate, PR, QRS, QT and QTcF.
Safety - Occurrence of Injection site reactions From time zero to 28 days after dosing Occurrence of injection site reactions
Safety - Immunogenicity: Occurrence of anti-drug antibodies From time zero to 28 days after dosing Occurrence of anti-drug antibodies
Trial Locations
- Locations (1)
Profil Institut für Stoffwechselforschung GmbH
🇩🇪Neuss, North Rhine-Westphalia, Germany