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A Research Study Looking at the Safety of Multiple Doses of ZP8396 and How it Works in the Body of Healthy Participants

Primary Purpose

Overweight, Healthy Volunteers, Obese

Status

Recruiting

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

ZP8396

Drug: Placebo (ZP8396)

About this trial

This is an interventional treatment trial for Overweight

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Part 1: Body Mass Index (BMI) between 21.0 and 29.9 kg/m^2, both inclusive Glycosylated hemoglobin (HbA1c) below 5.7 percent Further inclusion criteria apply Part 2: Body Mass Index (BMI) between 27.0 and 39.9 kg/m^2, both inclusive Glycosylated hemoglobin (HbA1c) below 6.5 percent Further inclusion criteria apply Exclusion Criteria: Part 1: History of metabolic diseases more frequently associated with obesity, e.g. type-2-diabetes mellitus, hypertension, dyslipidemia, heart disease or stroke Systolic blood pressure below 90 mmHg or above 139 mmHg and/or diastolic blood pressure below 50 mmHg or above 89 mmHg Symptoms of arterial hypotension Further exclusion criteria apply Part 2: History of metabolic diseases more frequently associated with obesity, e.g. type-2-diabetes mellitus, hypertension, dyslipidemia, heart disease or stroke Systolic blood pressure below 90 mmHg or above 159 mmHg and/or diastolic blood pressure below 50 mmHg or above 99 mmHg Symptoms of arterial hypotension Further exclusion criteria apply

Sites / Locations

Profil Institut für Stoffwechselforschung GmbHRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ZP8396

Placebo (ZP8396)

Arm Description

Part 1: 2 dose cohorts are planned with 10 subjects in each; 7 participants in each cohort will receive active treatment. Part 2: 3 dose cohorts are planned with 16 subjects in each; 12 participants in each cohort will receive active treatment.

Part 1: In each of the 2 dose cohorts, 3 subjects will receive placebo. Part 2: In each of the 3 cohorts, 4 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. Samples will be taken at set time points throughout the trial.

Pharmacokinetics (PK) of ZP8396 (AUCinf)

Area under the plasma concentration-time curve from time zero to infinity. Samples will be taken at set time points throughout the trial.

Pharmacokinetics (PK) of ZP8396 (AUClast)

Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration. Samples will be taken at set time points throughout the trial.

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

Pharmacokinetics (PK) of ZP8396 (CL/f)

Apparent total clearance of the drug from plasma

Pharmacokinetics (PK) of ZP8396 (Ctrough)

Trough concentration measured pre-dose

Accumulation Ratio for AUCτ

Accumulation Ratio for Cmax

Pharmacodynamics (PD) of ZP8396 (Cmax acetaminophen)

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

Pharmacodynamics (PD) of ZP8396 (Tmax acetaminophen)

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

Pharmacodynamics (PD) of ZP8396 (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 (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 (Emax, 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 (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 (AUE, Plasma Glucose [PG], 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 (AUE, Plasma Glucose [PG], 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 (Emax, 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 (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 (AUEinsulin,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 (AUEinsulin,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 (Emax, 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 (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 (AUEglucagon,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 (AUEglucagon,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

NCT05613387

First Posted

October 28, 2022

Last Updated

June 2, 2023

Sponsor

Zealand Pharma

1. Study Identification

Unique Protocol Identification Number

NCT05613387

Brief Title

A Research Study Looking at the Safety of Multiple Doses of ZP8396 and How it Works in the Body of Healthy Participants

Official Title

A Randomized, Multiple Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZP8396 Administered to Healthy Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 7, 2022 (Actual)

Primary Completion Date

May 2024 (Anticipated)

Study Completion Date

May 2024 (Anticipated)

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 trial is a single-centre, randomised and double-blind within cohorts, placebo-controlled, sequential multiple ascending dose trial in normal weight and overweight but otherwise healthy subjects randomised to subcutaneous administration of ZP8396 or placebo

Detailed Description

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). The trial is divided in two parts: Part 1: 20 Participants will receive 6 once-weekly doses as an injection under the skin (subcutaneous, s.c.). Participants will have 14 visits with the study team. 6 of these visits consists of overnight stays of different duration (2-4 nights) at the study site. For each participant, the study will last up to 116 days. Part 2: 48 Participants will receive 16 once-weekly doses as an injection under the skin (subcutaneous, s.c.) in a dose up-titration dose scheme. Participants will have 23 or 24 visits with the study team. 13 of these visits consists of overnight stays of different duration (2-4 nights) at the study site. For each participant, the study will last up to 191 days.

6. Conditions and Keywords

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

Overweight, Healthy Volunteers, Obese

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

Part 1: A single-centre, placebo-controlled, double-blind (within cohorts), randomised multiple ascending dose trial. Part 2: A single-centre, placebo-controlled, double-blind (within cohorts), randomised multiple ascending dose trial, using dose up-titration.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ZP8396

Arm Type

Experimental

Arm Description

Arm Title

Placebo (ZP8396)

Arm Type

Placebo Comparator

Arm Description

Part 1: In each of the 2 dose cohorts, 3 subjects will receive placebo. Part 2: In each of the 3 cohorts, 4 subjects will receive placebo.

Intervention Type

Drug

Intervention Name(s)

ZP8396

Intervention Description

Part 1: Participants will receive 6 once-weekly doses of ZP8396 given subcutaneously (s.c., under the skin). Dose level will depend on the cohort. Part 2: Participants will receive 16 once-weekly doses of ZP8396 given subcutaneously (s.c., under the skin). Dose level will depend on the cohort. Dose up-titration will be used.

Intervention Type

Drug

Intervention Name(s)

Drug: Placebo (ZP8396)

Intervention Description

Part 1: Participants will receive 6 once-weekly doses of placebo given subcutaneously (s.c., under the skin). Part 2: Participants will receive 16 once-weekly doses of placebo given subcutaneously (s.c., under the skin).

Primary Outcome Measure Information:

Title

Incidence of treatment emergent adverse events (TEAEs)

Time Frame

Part 1: From dosing (Day 1) to end of trial (Day 92); Part 2: From dosing (Day 1) to end of trial (Day 169)

Secondary Outcome Measure Information:

Title

Pharmacokinetics (PK) of ZP8396 (AUCτ)

Description

Area under the plasma concentration-time curve over a dosing interval. Samples will be taken at set time points throughout the trial.

Time Frame