Clinical trial NCT03994549: A Single Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Healthy
Keywords: Dual GLP-1R/GLP-2 Receptor agonist
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
First posted: 2019-06-21
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, double-blind, placebo-controlled, single ascending dose trial in healthy subjects, randomized to ZP7570 or placebo
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety - Incidence of adverse events (AEs)
timeFrame: From time zero to 28 days after dosing
Secondary outcomes:
measure: Pharmacokinetics - Area under the plasma concentration-time curve trough
timeFrame: From time zero up to day 28
measure: Pharmacokinetics - Area under the plasma concentration-time curve infinity
timeFrame: From time zero up to day 28
measure: Pharmacokinetics - Area under the plasma concentration-time curve last
timeFrame: From time zero up to day 28
measure: Pharmacokinetics - Maximum plasma concentration
timeFrame: From time zero to 28 days after dosing
measure: Pharmacokinetics - Time to maximum plasma concentration (Tmax)
timeFrame: From time zero to 28 days after dosing
measure: Pharmacokinetics - Half-life , t½
timeFrame: From time zero to 28 days after dosing
measure: Pharmacokinetics - Volume of distribution
timeFrame: From time zero to 28 days after dosing
measure: Pharmacokinetics - Mean residence time
timeFrame: From time zero to 28 days after dosing
measure: Pharmacokinetics - Body clearance
timeFrame: From time zero to 28 days after dosing
measure: Pharmacokinetics - Elimination rate constant
timeFrame: From time zero to 28 days after dosing
measure: Pharmacodynamics - Plasma glucose levels
timeFrame: Time Frame: 0-240 minutes
measure: Pharmacodynamics - Insulin concentrations
timeFrame: Time Frame: 0-240 minutes
measure: Pharmacodynamics - Plasma acetaminophen concentration-time curves
timeFrame: Time Frame: 0-240 minutes
measure: Pharmacodynamics - Maximum acetaminophen concentration
timeFrame: Time Frame: 0-240 minutes
measure: Pharmacodynamics - Time maximum acetaminophen concentration
timeFrame: Time Frame: 0-240 minutes
measure: Safety - Safety lab, haematology
timeFrame: From time zero to 28 days after dosing
measure: Safety - Safety lab, clinical chemistry
timeFrame: From time zero to 28 days after dosing
measure: Safety - Safety lab, urinalysis
timeFrame: From time zero to 28 days after dosing
measure: Safety - Vital signs, blood pressure
timeFrame: From time zero to 28 days after dosing
measure: Safety - Vital signs, pulse
timeFrame: From time zero to 28 days after dosing
measure: Safety - Physical examination
timeFrame: From time zero to 28 days after dosing
measure: Safety - ECG
timeFrame: From time zero to 28 days after dosing
measure: Safety - Occurrence of Injection site reactions
timeFrame: From time zero to 28 days after dosing
measure: Safety - Immunogenicity: Occurrence of anti-drug antibodies
timeFrame: From time zero to 28 days after dosing
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
state: North Rhine-Westphalia
Study officials:
affiliation: Profil Neuss, Germany
name: Ulrike Hövelmann, MD
role: PRINCIPAL_INVESTIGATOR
References: