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出境医 / 临床实验 / A Single Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570
A Single Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570
Study Description
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Healthy | Drug: Dual GLP-1/GLP-2 Receptor agonists | Early Phase 1 |
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 Design
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 64 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | A randomized, double-blind, placebo-controlled, single ascending dose trial in healthy subjects, randomized to ZP7570 or placebo |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | June 14, 2019 |
| Actual Primary Completion Date : | November 2, 2020 |
| Actual Study Completion Date : | November 2, 2020 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Active Comparator: ZP7570
Single subcutaneous injection
|
Drug: Dual GLP-1/GLP-2 Receptor agonists
Eight ascending doses of ZP7570
Other Name: ZP7570
|
|
Placebo Comparator: Placebo
Single subcutaneous injection
|
Drug: Dual GLP-1/GLP-2 Receptor agonists
Eight ascending doses of ZP7570
Other Name: ZP7570
|
Outcome Measures
Primary Outcome Measures :
- Safety - Incidence of adverse events (AEs) [ Time Frame: From time zero to 28 days after dosing ]The incidence, type and severity of adverse events (AEs)
Secondary Outcome Measures :
- Pharmacokinetics - Area under the plasma concentration-time curve trough [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From time zero to 28 days after dosing ]Measured maximum plasma drug concentration after dosing, Cmax
- Pharmacokinetics - Time to maximum plasma concentration (Tmax) [ Time Frame: From time zero to 28 days after dosing ]Sampling time until reaching Cmax, Tmax
- Pharmacokinetics - Half-life , t½ [ Time Frame: From time zero to 28 days after dosing ]Half-life of ZP7570, t½
- Pharmacokinetics - Volume of distribution [ Time Frame: From time zero to 28 days after dosing ]Apparent volume of distribution of ZP7570, Vz/f
- Pharmacokinetics - Mean residence time [ Time Frame: From time zero to 28 days after dosing ]Mean residence time, MRT
- Pharmacokinetics - Body clearance [ Time Frame: From time zero to 28 days after dosing ]Total body clearance, CL/f
- Pharmacokinetics - Elimination rate constant [ Time Frame: From time zero to 28 days after dosing ]Elimination rate constant, λz
- Pharmacodynamics - Plasma glucose levels [ Time Frame: 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: 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: Time Frame: 0-240 minutes ]Plasma acetaminophen concentration-time curves following ingestion of acetaminophen
- Pharmacodynamics - Maximum acetaminophen concentration [ Time Frame: Time Frame: 0-240 minutes ]Change from baseline acetaminophen to maximum acetaminophen
- Pharmacodynamics - Time maximum acetaminophen concentration [ Time Frame: Time Frame: 0-240 minutes ]Time to maximum change in acetaminophen measure from baseline, Tmax
- Safety - Safety lab, haematology [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From time zero to 28 days after dosing ]Changes in urinalysis: Protein, Glucose Erythrocytes, Leucocytes, pH, ketones
- Safety - Vital signs, blood pressure [ Time Frame: From time zero to 28 days after dosing ]Changes in vital signs, blood pressure (in mmHG)
- Safety - Vital signs, pulse [ Time Frame: From time zero to 28 days after dosing ]Changes in pulse (beats per minute)
- Safety - Physical examination [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From time zero to 28 days after dosing ]Occurrence of injection site reactions
- Safety - Immunogenicity: Occurrence of anti-drug antibodies [ Time Frame: From time zero to 28 days after dosing ]Occurrence of anti-drug antibodies
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
Contacts and Locations
Locations
| Germany | |
| Profil Institut für Stoffwechselforschung GmbH | |
| Neuss, North Rhine-Westphalia, Germany, 41460 | |
Sponsors and Collaborators
Zealand Pharma
Investigators
| Principal Investigator: | Ulrike Hövelmann, MD | Profil Neuss, Germany |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 15, 2019 | ||||
| First Posted Date ICMJE | June 21, 2019 | ||||
| Last Update Posted Date | December 2, 2020 | ||||
| Actual Study Start Date ICMJE | June 14, 2019 | ||||
| Actual Primary Completion Date | November 2, 2020 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Safety - Incidence of adverse events (AEs) [ Time Frame: From time zero to 28 days after dosing ] The incidence, type and severity of adverse events (AEs)
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | A Single Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570 | ||||
| Official Title ICMJE | 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 | ||||
| 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. | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Early Phase 1 | ||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: A randomized, double-blind, placebo-controlled, single ascending dose trial in healthy subjects, randomized to ZP7570 or placebo Masking: Triple (Participant, Investigator, Outcomes Assessor)Primary Purpose: Treatment |
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| Condition ICMJE | Healthy | ||||
| Intervention ICMJE | Drug: Dual GLP-1/GLP-2 Receptor agonists
Eight ascending doses of ZP7570
Other Name: ZP7570
|
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Completed | ||||
| Actual Enrollment ICMJE |
64 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Actual Study Completion Date ICMJE | November 2, 2020 | ||||
| Actual Primary Completion Date | November 2, 2020 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 55 Years (Adult) | ||||
| Accepts Healthy Volunteers ICMJE | Yes | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Listed Location Countries ICMJE | Germany | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03994549 | ||||
| Other Study ID Numbers ICMJE | ZP7570-18144 2019-001128-36 ( EudraCT Number ) |
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| Has Data Monitoring Committee | No | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Zealand Pharma | ||||
| Study Sponsor ICMJE | Zealand Pharma | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
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| PRS Account | Zealand Pharma | ||||
| Verification Date | November 2020 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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