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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05613387
• Other study ID #: ZP8396-21038
• Status: Completed
• Phase: Phase 1
• Start date: November 7, 2022
• Est. completion date: June 13, 2024

Study information

• Verified date: June 2024
• Source: Zealand Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: June 13, 2024
• Est. primary completion date: June 13, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers
• Obese
• Overweight

Intervention

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.
• 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).

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)	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	Pharmacokinetics (PK) of ZP8396 (AUCt)	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Pharmacokinetics (PK) of ZP8396 (?z)	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Accumulation Ratio for AUCt	Accumulation Ratio for AUCt	Part 1: Day 1 (pre-dose) to Day 92
Secondary	Accumulation Ratio for Cmax	Accumulation Ratio for Cmax	Part 1: Day 1 (pre-dose) to Day 92
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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