Healthy Volunteers, Overweight
Conditions
Brief summary
The research study will investigate the safety and tolerability of ZP8396 in healthy study participants. In addition, the study will investigate how ZP8396 works in the body (pharmacokinetics and pharmacodynamics). Participants will receive 1 single dose either as an injection under the skin (subcutaneous, s.c.) or an injection into a vein of one arm (intravenous, i.v.). Participants will have 9 visits with the study team. One of these visits consists of 8 overnight stays at the study site. For each participant, the study will last up to 66 days.
Interventions
DRUGZP8396
Participants will receive 1 single dose of ZP8396 given subcutaneously (s.c., under the skin) or intravenously (i.v., in a vein of the arm). Dose level will depend on the cohort.
DRUGPlacebo (ZP8396)
Participants will receive 1 single dose of placebo given subcutaneously (s.c., under the skin) or intravenously (i.v., in a vein of the arm).
Sponsors
Zealand Pharma
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
First human dose trial. A single-centre, placebo-controlled, double-blind (within cohorts), randomised single dose trial.
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subject * Body Mass Index (BMI) between 21.0 and 29.9 kg/m\^2, both inclusive * Body weight of at least 70.0 kg * Glycosylated hemoglobin A1c (HbA1c) less than 5.7 percent * Further inclusion criteria apply
Exclusion criteria
* History of metabolic diseases more frequently associated with obesity, e.g. type-2-diabetes mellitus, hypertension, dyslipidemia, heart disease or stroke * Systolic blood pressure \< 90 mmHg or \>139 mmHg and/or diastolic blood pressure less than 50 mmHg or greater than 89 mmHg * Symptoms of arterial hypotension * Further
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment emergent adverse events (TEAEs) | From dosing (Day 1) to end of trial (Day 50) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of ZP8396 (AUCinf) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Area under the plasma concentration-time curve from time zero to infinity |
| Pharmacokinetics (PK) of ZP8396 (AUClast) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration |
| Pharmacokinetics (PK) of ZP8396 (Cmax) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Maximum (peak) plasma drug concentration |
| Pharmacokinetics (PK) of ZP8396 (tmax) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Time to reach maximum (peak) plasma concentration |
| Pharmacokinetics (PK) of ZP8396 (λz) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Elimination rate constant |
| Pharmacokinetics (PK) of ZP8396 (t½) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Elimination half-life |
| Pharmacokinetics (PK) of ZP8396 (Vz/f) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Apparent volume of distribution during terminal phase |
| Pharmacokinetics (PK) of ZP8396 (Vz) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Volume of distribution during the terminal phase (i.v. only) |
| Pharmacokinetics (PK) of ZP8396 (CL/f) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Apparent total clearance of the drug from plasma |
| Pharmacokinetics (PK) of ZP8396 (CL) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Total body clearance of the drug (i.v. only) |
| Pharmacokinetics (PK) of ZP8396 (MRT) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Mean residence time |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax acetaminophen) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Tmax acetaminophen) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Time to maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacokinetics (PK) of ZP8396 (AUCτ) | Day 1 (pre-dose) to Day 50 (1176 hours post-dose) | Area under the plasma concentration-time curve over a dosing interval |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Tmax, Plasma Glucose [PG]) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Time to maximum PG concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCacetaminophen, 0-240 min) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Area under the acetaminophen concentration-time curve from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax, Plasma Glucose [PG]) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Maximum PG concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCPG,0-60 min) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Area under the Plasma Glucose (PG) concentration-time curve from 0 to 60 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCPG,0-240 min) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Area under the Plasma Glucose (PG) concentration-time curve from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax, insulin) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Maximum insulin concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Tmax, insulin) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Time to maximum insulin concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCinsulin,0-60 min) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Area under the insulin concentration-time curve from 0 to 60 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCinsulin,0-240 min) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Area under the insulin concentration-time curve from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax, glucagon) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Maximum glucagon concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Tmax, glucagon) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Time to maximum glucagon concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCglucagon,0-60 min) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Area under the glucagon concentration-time curve from 0 to 60 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCglucagon,0-240 min) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Area under the glucagon concentration-time curve from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
| Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCacetaminophen, 0-60 min) | 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5 | Area under the acetaminophen concentration-time curve from 0 to 60 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen |
Countries
Germany
Outcome results
None listed