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Completed

NCT Number: NCT05613387

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

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

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Key information

Conditions

Overweight Body Weight Healthy Volunteers Nutrition Disorders Nutritional and Metabolic Diseases Obese Obesity Overnutrition Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Profil Institut für Stoffwechselforschung GmbH

Neuss, North Rhine-Westphalia, 41460, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ZP8396

Drug

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)

Drug

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 outcomes

  1. 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 for Cohort 1 and 2, Day 176 for Cohort 3)

    Incidence of TEAEs from 1st dosing day to end of trial

Secondary outcomes

  1. Pharmacokinetics (PK) of ZP8396 (AUCτ)

    Time frame: 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

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

  2. Pharmacokinetics (PK) of ZP8396 (AUCinf)

    Time frame: 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

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

  3. Pharmacokinetics (PK) of ZP8396 (AUClast)

    Time frame: 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

    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.

  4. Pharmacokinetics (PK) of ZP8396 (Cmax)

    Time frame: 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

    Maximum (peak) plasma drug concentration

  5. Pharmacokinetics (PK) of ZP8396 (tmax)

    Time frame: 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

    Time to reach maximum (peak) plasma concentration

  6. Pharmacokinetics (PK) of ZP8396 (λz)

    Time frame: 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

    Elimination rate constant

  7. Pharmacokinetics (PK) of ZP8396 (t½)

    Time frame: 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

    Elimination half-life

  8. Pharmacokinetics (PK) of ZP8396 (Vz/f)

    Time frame: 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

    Apparent volume of distribution

  9. Pharmacokinetics (PK) of ZP8396 (CL/f)

    Time frame: 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

    Apparent total clearance of the drug from plasma

  10. Pharmacokinetics (PK) of ZP8396 (Ctrough)

    Time frame: 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

    Trough concentration measured pre-dose

  11. Accumulation Ratio for AUCτ

    Time frame: Part 1: Day 1 (pre-dose) to Day 92

    Accumulation Ratio for AUCτ

  12. Accumulation Ratio for Cmax

    Time frame: Part 1: Day 1 (pre-dose) to Day 92

    Accumulation Ratio for Cmax

  13. Pharmacodynamics (PD) of ZP8396 (Cmax acetaminophen)

    Time frame: 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

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

  14. Pharmacodynamics (PD) of ZP8396 (Tmax acetaminophen)

    Time frame: 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

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

  15. Pharmacodynamics (PD) of ZP8396 (AUCacetaminophen, 0-60 min)

    Time frame: 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

    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

  16. Pharmacodynamics (PD) of ZP8396 (AUCacetaminophen, 0-240 min)

    Time frame: 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

    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

  17. Pharmacodynamics (PD) of ZP8396 (Emax, Plasma Glucose [PG])

    Time frame: 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

    Maximum PG concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen

  18. Pharmacodynamics (PD) of ZP8396 (Tmax, Plasma Glucose [PG])

    Time frame: 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

    Time to maximum PG concentration from 0 to 240 minutes after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen

  19. Pharmacodynamics (PD) of ZP8396 (AUE, Plasma Glucose [PG], 0-60 minutes)

    Time frame: 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

    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

  20. Pharmacodynamics (PD) of ZP8396 (AUE, Plasma Glucose [PG], 0-240 minutes)

    Time frame: 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

    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

  21. Pharmacodynamics (PD) of ZP8396 (Emax, insulin)

    Time frame: Part 1: 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

  22. Pharmacodynamics (PD) of ZP8396 (Tmax, insulin)

    Time frame: Part 1: 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

  23. Pharmacodynamics (PD) of ZP8396 (AUEinsulin,0-60 minutes)

    Time frame: Part 1: 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

  24. Pharmacodynamics (PD) of ZP8396 (AUEinsulin,0-240 min)

    Time frame: Part 1: 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

  25. Pharmacodynamics (PD) of ZP8396 (Emax, glucagon)

    Time frame: Part 1: 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

  26. Pharmacodynamics (PD) of ZP8396 (Tmax, glucagon)

    Time frame: Part 1: 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

  27. Pharmacodynamics (PD) of ZP8396 (AUEglucagon,0-60 minutes)

    Time frame: Part 1: 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

  28. Pharmacodynamics (PD) of ZP8396 (AUEglucagon,0-240 minutes)

    Time frame: Part 1: 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

Sponsors and collaborators

Lead sponsor

Zealand Pharma

Industry

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Nov 14, 2022
Registry last updated
Jun 18, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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