A First-in-human Study Looking at the Safety of ZP8396 and How it Works in the Body of Healthy Trial Participants

Healthy Volunteers Clinical Trial

Official title:

A First-in-human, Randomised, Single Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZP8396 Administered to Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05096598
• Other study ID #: ZP8396-21037
• Secondary ID: 2021-001712-28U1
• Status: Completed
• Phase: Phase 1
• Start date: October 19, 2021
• Est. completion date: January 12, 2023

Study information

• Verified date: January 2023
• Source: Zealand Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: January 12, 2023
• Est. primary completion date: January 12, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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 exclusion criteria apply

Related Conditions & MeSH terms

• Healthy Volunteers
• Overweight

Intervention

Drug:
• ZP8396
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.
• Placebo (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).

Locations

Country	Name	City	State
Germany	Profil Institut für Stoffwechselforschung GmbH	Neuss	North Rhine-Westphalia

Sponsors (1)

Lead Sponsor	Collaborator
Zealand Pharma

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events (TEAEs)		From dosing (Day 1) to end of trial (Day 50)
Secondary	Pharmacokinetics (PK) of ZP8396 (AUCt)	Area under the plasma concentration-time curve over a dosing interval	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (AUCinf)	Area under the plasma concentration-time curve from time zero to infinity	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (AUClast)	Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (Cmax)	Maximum (peak) plasma drug concentration	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (tmax)	Time to reach maximum (peak) plasma concentration	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (?z)	Elimination rate constant	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (t½)	Elimination half-life	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (Vz/f)	Apparent volume of distribution during terminal phase	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (Vz)	Volume of distribution during the terminal phase (i.v. only)	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (CL/f)	Apparent total clearance of the drug from plasma	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (CL)	Total body clearance of the drug (i.v. only)	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacokinetics (PK) of ZP8396 (MRT)	Mean residence time	Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax acetaminophen)	Maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Tmax acetaminophen)	Time to maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCacetaminophen, 0-60 min)	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	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCacetaminophen, 0-240 min)	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	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax, Plasma Glucose [PG])	Maximum PG concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Tmax, Plasma Glucose [PG])	Time to maximum PG concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCPG,0-60 min)	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	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCPG,0-240 min)	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	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax, insulin)	Maximum insulin concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Tmax, insulin)	Time to maximum insulin concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCinsulin,0-60 min)	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	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCinsulin,0-240 min)	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	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax, glucagon)	Maximum glucagon concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Tmax, glucagon)	Time to maximum glucagon concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCglucagon,0-60 min)	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	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
Secondary	Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCglucagon,0-240 min)	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	0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5