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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dual GLP-1/GLP-2 Receptor agonists

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Germany
  • North Rhine-Westphalia
    • Neuss, North Rhine-Westphalia, Germany, 41460
      • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zealand Pharma
• Investigators: Principal Investigator: Ulrike Hövelmann, MD, Profil Neuss, Germany

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2019
• Primary Completion (Actual): November 2, 2020
• Study Completion (Actual): November 2, 2020

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): December 2, 2020
• Last Update Submitted That Met QC Criteria: December 1, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Dual GLP-1R/GLP-2 Receptor agonist
• Other Study ID Numbers: ZP7570-18144; 2019-001128-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No