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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001129-29 | EudraCT Number |
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This is a randomised, double-blind, placebo-controlled, multiple ascending dose trial in healthy subjects, randomised to ZP7570 or placebo within each cohort
Forty subjects are planned to be studied in four cohorts in this multiple ascending dose trial. Ten subjects will be allocated to four dose levels. Intermediate dose levels may be applied. A sentinel dosing approach (sequential dosing) will be applied. The entire observation period comprises 51 days starting with a 96 hours in-house stay after the first dose injection, where discharge is planned for Day 5, followed by one outpatient visit. For the second and the third injection dose a 36 hours in-house stay is planned. After the fourth dose injection there is also a 96 hour in-house stay where discharge is planned for Day 26, followed by five outpatient visits and an End of Trial Visit on Day 51. A blinded evaluation of each cohort will be performed by a Trial Safety Group to determine whether the trial will progress to the next planned dose level based on the stopping rules specified in the protocol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ZP7570 | Experimental | Four ascending doses of ZP7570 |
|
| Placebo | Placebo Comparator | Corresponding volume of placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZP7570 | Drug | Each subject will be randomly allocated to multiple doses of ZP7570 at one of four dose levels in each cohort. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability - Incidence of treatment emergent adverse events as assessed by type and severity | The incidence, type and severity of treatment emergent adverse events | From time 0 to 51 days after first dosing (29 days after fourth dosing) ] |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics - Area under the plasma concentration-time curve - through | AUCτ, Area under the plasma concentration-time curve from zero to through concentration. | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacokinetics - Area under the plasma concentration-time curve - infinity |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ulrike Hövelmann | Profil Institut für Stoffwechselforschung GmbH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Profil Institut für Stoffwechselforschung GmbH | Neuss | North Rhine-Westphalia | 41460 | Germany |
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A randomized, double-blind, placebo-controlled, single ascending dose trial in healthy subjects, randomized to ZP7570 or placebo
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| Placebo | Drug | Placebo; corresponding volume |
|
AUCinf, Area under the plasma concentration-time curve from zero to infinity concentration. |
| From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacokinetics - Area under the plasma concentration-time curve - last | AUClast, Area under the plasma concentration-time curve-from zero to last concentration. | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacokinetics - Maximum plasma concentration - Cmax | Cmax, Measured maximum plasma drug concentration after dosing | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacokinetics - Time to maximum plasma concentration - Tmax | Tmax, Sampling time until reaching Cmax after dosing | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacokinetics - Elimination rate constant - λz | λz, Elimination rate constant | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacokinetics - Half-life - t½ | t½, Half-life of ZP7570 | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacokinetics - Volume of distribution - Vz/f | Vz/f, Apparent volume of distribution of ZP7570 during terminal phase | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacokinetics - Body clearance - CL/f | CL/f, Apparent total body clearance | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacokinetics - Mean residence time - MRT | MRT, Mean residence time | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Pharmacodynamics - Acetaminophen concentration-time curves | Acetaminophen concentration-time curves following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the the forth dose |
| Pharmacodynamics - Maximum acetaminophen concentration - Cmax | Cmax, maximum acetaminophen concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the the forth dose |
| Pharmacodynamics - Time to maximum acetaminophen concentration - Tmax | Tmax, Time to maximum acetaminophen concentration following ingestion of mixed meal test and acetaminophene | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCacetaminohen,0-60min | AUCacetaminohen,0-60min, area under the acetaminophen concentration-time curve from 0 to 60 min post-ingestion | From time 0 to 60 minutes at baseline, 24 hours after a single dose and 24 hours after the the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCacetaminohen,0-240min | AUCacetaminohen,0-240min, area under the acetaminophen concentration -time curve from 0 to 240 min post-ingestion | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Plasma glucose concentration-time curves | Plasma glucose concentration-time curves following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the the forth dose |
| Pharmacodynamics - Maximum plasma glucose concentration - Cmax | Cmax, Maximum plasma glucose concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the the forth dose |
| Pharmacodynamics - Time to maximum plasma glucose concentration - Tmax | Tmax, Time to maximum plasma glucose concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCplasma glucose,0-60min | AUCplasma glucose,0-60min, area under the plasma glucose concentration-time curve from 0 to 60 min post-ingestion | From time 0 to 60 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCplasma glucose,0-240min | AUCplasma glucose,0-240min, area under the acetaminophen concentration -time curve from 0 to 240 min post-ingestion | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Insulin concentration-time curves | Insulin concentration-time curves following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Maximum insulin concentration - Cmax | Cmax, Maximum insulin concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Time to maximum insulin concentration - Tmax | Tmax, Time to maximum insulin concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCinsulin,0-60min | AUCinsulin,0-60min, area under the insulin concentration-time curve from 0 to 60 min post-ingestion | From time 0 to 60 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCinsulin, 0-240min | AUCinsulin,0-240min, area under the insulin concentration-time curve from 0 to 240 min post-ingestion | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Glucagon concentration-time curves (optional) | Glucagon concentration-time curves following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Maximum glucagon concentration - Cmax (optional) | Cmax, Maximum glucagon concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Time to maximum glucagon concentration - Tmax (optional) | Tmax, Time to maximum glucagon concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCglucagon,0-60min (optional) | AUCglucagon,0-60min, area under the glucagon concentration-time curve from 0 to 60 min post-ingestion | From time 0 to 60 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCglucagon, 0-240min (optional) | AUCglucagon,0-240min, area under the glucagon concentration-time curve from 0 to 240 min post-ingestion | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Free fatty acids concentration-time curves | Free fatty acids concentration-time curves following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Maximum free fatty acids concentration - Cmax | Cmax, Maximum free fatty acids concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Time to maximum free fatty acids concentration - Tmax | Tmax, Time to maximum free fatty acids concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCfree fatty acids, 0-60min | AUCfree fatty acids,0-60min, area under the free fatty acids concentration-time curve | From time 0 to 60 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCfree fatty acids, 0-240min | AUCfree fatty acids,0-240min, area under the free fatty acids concentration-time curve | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Triglycerides concentration-time curves | Triglycerides concentration-time curves following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Maximum triglycerides concentration - Cmax | Cmax, Maximum triglycerides concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Time to maximum triglycerides concentration - Tmax | Tmax, Time to maximum triglycerides concentration following ingestion of mixed meal test and acetaminophen | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCtriglycerides, 0-60min | AUCtriglycerides,0-60min, area under the triglycerides concentration-time | From time 0 to 60 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Pharmacodynamics - Area under the concentration-time curve - AUCtriglycerides,0-240min | AUCtriglycerides,0-240min, area under the triglycerides concentration-time curve | From time 0 to 240 minutes at baseline, 24 hours after a single dose and 24 hours after the forth dose |
| Anti-ZP7570 antibodies - Incidence and titres | Overall anti-ZP7570 antibody incidence and titers. Incidence of anti-ZP7570 antibodies cross-reacting with endogenous GLP-1 or GLP-2. | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Safety Lab - Haematological values vs. reference ranges and baseline | Abnormal values or changes in haematology. | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Safety Lab - Clinical chemistry values vs. reference ranges and baseline | Abnormal values or changes in chemical chemistry | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Safety Lab - Urinalysis values vs. reference ranges and baseline | Abnormal values or changes in urinalysis | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Safety - Vital signs: blood pressure | Changes in diastolic and systolic blood pressure (in mmHg) | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Safety - Vital signs: pulse | Changes in pulse (beats per minute) | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Safety - Physical Examination | Changes in physical examination of the body. Outcome will be measured as 'normal' or 'abnormal', if abnormal as 'not clinically significant' or 'clinically significant'. | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Safety - ECG | Changes or abnormalities in ECG parameters (in ms): Heart rate, PR, QRS, QT, QTcF | From time 0 to 51 days after first dosing (29 days after fourth dosing) |
| Safety - Injection site reactions | Occurrence of injection site reactions | From time 0 to 51 days after first dosing (29 days after fourth dosing) |