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

Sponsor

Zealand Pharma (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05613387

Collaborator

(none)

Enrollment

Location

Arms

7.8

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Overweight Healthy Volunteers	Drug: ZP8396 Drug: Drug: Placebo (ZP8396)	Phase 1

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).

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 7, 2022

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ZP8396 Up to 3 dose cohorts are planned with 10 subjects in each; 7 participants in each cohort will receive active treatment.	Drug: ZP8396 Participants will receive 6 once-weekly doses of ZP8396 given subcutaneously (s.c., under the skin). Dose level will depend on the cohort.
Placebo Comparator: Placebo (ZP8396) In each of the 3 dose cohorts, 3 subjects will receive placebo.	Drug: Drug: Placebo (ZP8396) Participants will receive 6 once-weekly doses of placebo given subcutaneously (s.c., under the skin).

Arm

Intervention/Treatment

Experimental: ZP8396

Up to 3 dose cohorts are planned with 10 subjects in each; 7 participants in each cohort will receive active treatment.

Drug: ZP8396

Participants will receive 6 once-weekly doses of ZP8396 given subcutaneously (s.c., under the skin). Dose level will depend on the cohort.

Placebo Comparator: Placebo (ZP8396)

In each of the 3 dose cohorts, 3 subjects will receive placebo.

Drug: Drug: Placebo (ZP8396)

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

Outcome Measures

Primary Outcome Measures

Incidence of treatment emergent adverse events (TEAEs) [From dosing (Day 1) to end of trial (Day 92)]

Secondary Outcome Measures

Pharmacokinetics (PK) of ZP8396 (AUCτ) [Day 1 (pre-dose) to Day 92]
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) [Day 1 (pre-dose) to Day 92]
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) [Day 1 (pre-dose) to Day 92]
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) [Day 1 (pre-dose) to Day 92]
Maximum (peak) plasma drug concentration
Pharmacokinetics (PK) of ZP8396 (tmax) [Day 1 (pre-dose) to Day 92]
Time to reach maximum (peak) plasma concentration
Pharmacokinetics (PK) of ZP8396 (λz) [Day 1 (pre-dose) to Day 92]
Elimination rate constant
Pharmacokinetics (PK) of ZP8396 (t½) [Day 1 (pre-dose) to Day 92]
Elimination half-life
Pharmacokinetics (PK) of ZP8396 (Vz/f) [Day 1 (pre-dose) to Day 92]
Apparent volume of distribution
Pharmacokinetics (PK) of ZP8396 (CL/f) [Day 1 (pre-dose) to Day 92]
Apparent total clearance of the drug from plasma
Pharmacokinetics (PK) of ZP8396 (Ctrough) [Day 1 (pre-dose) to Day 92]
Trough concentration measured pre-dose
Accumulation Ratio for AUCτ [Day 1 (pre-dose) to Day 92]
Accumulation Ratio for AUCτ
Accumulation Ratio for Cmax [Day 1 (pre-dose) to Day 92]
Accumulation Ratio for Cmax
Pharmacodynamics (PD) of ZP8396 (Cmax acetaminophen) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
Maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen
Pharmacodynamics (PD) of ZP8396 (Tmax acetaminophen) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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]) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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]) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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) [0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

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 below 90 mmHg or above139 mmHg and/or diastolic blood pressure below 50 mmHg or above 89 mmHg
Symptoms of arterial hypotension
Further exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Profil Institut für Stoffwechselforschung GmbH	Neuss	North Rhine-Westphalia	Germany	41460

Sponsors and Collaborators

Zealand Pharma

Investigators

Study Director: Zealand Pharma A/S, Zealand Pharma A/S

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Zealand Pharma

ClinicalTrials.gov Identifier:

NCT05613387

Other Study ID Numbers:

ZP8396-21038

First Posted:

Nov 14, 2022

Last Update Posted:

Nov 17, 2022

Last Verified:

Nov 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Overweight

Study Results

No Results Posted as of Nov 17, 2022