Back to results

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

Primary Purpose

Overweight, Healthy Volunteers

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

ZP8396

Placebo (ZP8396)

About this trial

This is an interventional treatment trial for Overweight

Eligibility Criteria

18 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

Profil Institut für Stoffwechselforschung GmbH

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ZP8396

Placebo (ZP8396)

Arm Description

Up to 10 single dose cohorts are planned with 8 subjects in each; 6 participants in each cohort will receive active treatment.

In each of the 10 single dose cohorts, 2 subjects will receive placebo.

Outcomes

Primary Outcome Measures

Incidence of treatment emergent adverse events (TEAEs)

Secondary Outcome Measures

Pharmacokinetics (PK) of ZP8396 (AUCτ)

Area under the plasma concentration-time curve over a dosing interval

Pharmacokinetics (PK) of ZP8396 (AUCinf)

Area under the plasma concentration-time curve from time zero to infinity

Pharmacokinetics (PK) of ZP8396 (AUClast)

Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration

Pharmacokinetics (PK) of ZP8396 (Cmax)

Maximum (peak) plasma drug concentration

Pharmacokinetics (PK) of ZP8396 (tmax)

Time to reach maximum (peak) plasma concentration

Pharmacokinetics (PK) of ZP8396 (λz)

Elimination rate constant

Pharmacokinetics (PK) of ZP8396 (t½)

Elimination half-life

Pharmacokinetics (PK) of ZP8396 (Vz/f)

Apparent volume of distribution during terminal phase

Pharmacokinetics (PK) of ZP8396 (Vz)

Volume of distribution during the terminal phase (i.v. only)

Pharmacokinetics (PK) of ZP8396 (CL/f)

Apparent total clearance of the drug from plasma

Pharmacokinetics (PK) of ZP8396 (CL)

Total body clearance of the drug (i.v. only)

Pharmacokinetics (PK) of ZP8396 (MRT)

Mean residence time

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Full Information

NCT ID

NCT05096598

First Posted

October 14, 2021

Last Updated

January 13, 2023

Sponsor

Zealand Pharma

1. Study Identification

Unique Protocol Identification Number

NCT05096598

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

October 19, 2021 (Actual)

Primary Completion Date

January 12, 2023 (Actual)

Study Completion Date

January 12, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Zealand Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Overweight, Healthy Volunteers

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

First human dose trial. A single-centre, placebo-controlled, double-blind (within cohorts), randomised single dose trial.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

64 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ZP8396

Arm Type

Experimental

Arm Description

Up to 10 single dose cohorts are planned with 8 subjects in each; 6 participants in each cohort will receive active treatment.

Arm Title

Placebo (ZP8396)

Arm Type

Placebo Comparator

Arm Description

In each of the 10 single dose cohorts, 2 subjects will receive placebo.

Intervention Type

Drug

Intervention Name(s)

ZP8396

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo (ZP8396)

Intervention Description

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).

Primary Outcome Measure Information:

Title

Incidence of treatment emergent adverse events (TEAEs)

Time Frame

From dosing (Day 1) to end of trial (Day 50)

Secondary Outcome Measure Information:

Title

Pharmacokinetics (PK) of ZP8396 (AUCτ)

Description

Area under the plasma concentration-time curve over a dosing interval

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (AUCinf)

Description

Area under the plasma concentration-time curve from time zero to infinity

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (AUClast)

Description

Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (Cmax)

Description

Maximum (peak) plasma drug concentration

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (tmax)

Description

Time to reach maximum (peak) plasma concentration

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (λz)

Description

Elimination rate constant

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (t½)

Description

Elimination half-life

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (Vz/f)

Description

Apparent volume of distribution during terminal phase

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (Vz)

Description

Volume of distribution during the terminal phase (i.v. only)

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (CL/f)

Description

Apparent total clearance of the drug from plasma

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (CL)

Description

Total body clearance of the drug (i.v. only)

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacokinetics (PK) of ZP8396 (MRT)

Description

Mean residence time

Time Frame

Day 1 (pre-dose) to Day 50 (1176 hours post-dose)

Title

Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax acetaminophen)

Description

Maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen

Time Frame