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

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

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

Study Overview

• Status: Completed
• Conditions: Overweight; Healthy Volunteers; Obese
• Intervention / Treatment: Drug: ZP8396; Drug: Drug: Placebo (ZP8396)

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 198 days.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • North Rhine-Westphalia
    • Neuss, North Rhine-Westphalia, Germany, 41460
      • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZP8396; 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.	Drug: ZP8396; 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.
Placebo Comparator: Placebo (ZP8396); 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.	Drug: Drug: Placebo (ZP8396); 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment emergent adverse events (TEAEs)	Incidence of TEAEs from 1st dosing day to end of trial	Part 1: From dosing (Day 1) to end of trial (Day 92); Part 2: From dosing (Day 1) to end of trial (Day 169 for Cohort 1 and 2, Day 176 for Cohort 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accumulation Ratio for AUCτ	Accumulation Ratio for AUCτ	Part 1: Day 1 (pre-dose) to Day 92
Accumulation Ratio for Cmax	Accumulation Ratio for Cmax	Part 1: Day 1 (pre-dose) to Day 92
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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
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.	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
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.	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
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.	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
Pharmacokinetics (PK) of ZP8396 (Cmax)	Maximum (peak) plasma drug concentration	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
Pharmacokinetics (PK) of ZP8396 (tmax)	Time to reach maximum (peak) plasma concentration	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
Pharmacokinetics (PK) of ZP8396 (λz)	Elimination rate constant	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
Pharmacokinetics (PK) of ZP8396 (t½)	Elimination half-life	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
Pharmacokinetics (PK) of ZP8396 (Vz/f)	Apparent volume of distribution	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
Pharmacokinetics (PK) of ZP8396 (CL/f)	Apparent total clearance of the drug from plasma	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
Pharmacokinetics (PK) of ZP8396 (Ctrough)	Trough concentration measured pre-dose	Part 1: Day 1 (pre-dose) to Day 92; Part 2: Day 1 (pre-dose) to Day 169 for Cohort 1 and 2, Day 176 for Cohort 3
Pharmacodynamics (PD) of ZP8396 (Cmax acetaminophen)	Maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40; Part 2: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1, Day 110 for cohort 1 and 2, Day -1, Day 1, Day 107 for cohort 3
Pharmacodynamics (PD) of ZP8396 (Tmax acetaminophen)	Time to maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40; Part 2: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1, Day 110 for cohort 1 and 2, Day -1, Day 1, Day 107 for cohort 3
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	Part 1: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40; Part 2: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1, Day 110 for cohort 1 and 2, Day -1, Day 1, Day 107 for cohort 3
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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40; Part 2: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1, Day 110 for cohort 1 and 2, Day -1, Day 1, Day 107 for cohort 3
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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40; Part 2: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1, Day 110 for cohort 1 and 2, Day -1, Day 1, Day 107 for cohort 3
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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40; Part 2: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1, Day 110 for cohort 1 and 2, Day -1, Day 1, Day 107 for cohort 3
Pharmacodynamics (PD) of ZP8396 (AUE, Plasma Glucose [PG], 0-60 minutes)	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	Part 1: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40; Part 2: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1, Day 110 for cohort 1 and 2, Day -1, Day 1, Day 107 for cohort 3
Pharmacodynamics (PD) of ZP8396 (AUE, Plasma Glucose [PG], 0-240 minutes)	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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40; Part 2: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1, Day 110 for cohort 1 and 2, Day -1, Day 1, Day 107 for cohort 3
Pharmacodynamics (PD) of ZP8396 (AUEinsulin,0-60 minutes)	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	Part 1: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
Pharmacodynamics (PD) of ZP8396 (AUEglucagon,0-60 minutes)	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	Part 1: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
Pharmacodynamics (PD) of ZP8396 (AUEglucagon,0-240 minutes)	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	Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40

Collaborators and Investigators

• Sponsor: Zealand Pharma
• Investigators: Study Director: Zealand Pharma A/S, Zealand Pharma A/S

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2022
• Primary Completion (Actual): June 13, 2024
• Study Completion (Actual): June 13, 2024

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 4, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Overweight
• Other Study ID Numbers: ZP8396-21038

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No