A First-in-human Study Looking at the Safety of ZP8396 and How it Works in the Body of Healthy Trial Participants

Overview

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 1 single dose either as an injection under the skin (subcutaneous, s.c.) or an injection into a vein of one arm (intravenous, i.v.). Participants will have 9 visits with the study team. One of these visits consists of 8 overnight stays at the study site. For each participant, the study will last up to 66 days.

Full Title of Study: “A First-in-human, Randomised, Single Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZP8396 Administered to Healthy Subjects”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Sequential Assignment
  • Primary Purpose: Treatment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Study Primary Completion Date: January 12, 2023

Interventions

• Drug: ZP8396
  • Participants will receive 1 single dose of ZP8396 given subcutaneously (s.c., under the skin) or intravenously (i.v., in a vein of the arm). Dose level will depend on the cohort.
• Drug: Placebo (ZP8396)
  • Participants will receive 1 single dose of placebo given subcutaneously (s.c., under the skin) or intravenously (i.v., in a vein of the arm).

Arms, Groups and Cohorts

• Experimental: ZP8396
  • Up to 10 single dose cohorts are planned with 8 subjects in each; 6 participants in each cohort will receive active treatment.
• Placebo Comparator: Placebo (ZP8396)
  • In each of the 10 single dose cohorts, 2 subjects will receive placebo.

Clinical Trial Outcome Measures

Primary Measures

• Incidence of treatment emergent adverse events (TEAEs)
  • Time Frame: From dosing (Day 1) to end of trial (Day 50)

Secondary Measures

• Pharmacokinetics (PK) of ZP8396 (AUCτ)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Area under the plasma concentration-time curve over a dosing interval
• Pharmacokinetics (PK) of ZP8396 (AUCinf)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Area under the plasma concentration-time curve from time zero to infinity
• Pharmacokinetics (PK) of ZP8396 (AUClast)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration
• Pharmacokinetics (PK) of ZP8396 (Cmax)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Maximum (peak) plasma drug concentration
• Pharmacokinetics (PK) of ZP8396 (tmax)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Time to reach maximum (peak) plasma concentration
• Pharmacokinetics (PK) of ZP8396 (λz)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Elimination rate constant
• Pharmacokinetics (PK) of ZP8396 (t½)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Elimination half-life
• Pharmacokinetics (PK) of ZP8396 (Vz/f)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Apparent volume of distribution during terminal phase
• Pharmacokinetics (PK) of ZP8396 (Vz)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Volume of distribution during the terminal phase (i.v. only)
• Pharmacokinetics (PK) of ZP8396 (CL/f)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Apparent total clearance of the drug from plasma
• Pharmacokinetics (PK) of ZP8396 (CL)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Total body clearance of the drug (i.v. only)
• Pharmacokinetics (PK) of ZP8396 (MRT)
  • Time Frame: Day 1 (pre-dose) to Day 50 (1176 hours post-dose)
  • Mean residence time
• Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Cmax acetaminophen)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • Maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen
• Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (Tmax acetaminophen)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • Time to maximum acetaminophen concentration after ingestion of a standardised Mixed Test Meal (MTM) and 1000 mg acetaminophen
• Pharmacodynamics (PD) of ZP8396, for dose cohorts greater than or equal to 0.7 mg (AUCacetaminophen, 0-60 min)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (AUCacetaminophen, 0-240 min)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (Cmax, Plasma Glucose [PG])
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (Tmax, Plasma Glucose [PG])
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (AUCPG,0-60 min)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • Area under the Plasma Glucose (PG) 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, for dose cohorts greater than or equal to 0.7 mg (AUCPG,0-240 min)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • Area under the Plasma Glucose (PG) 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, for dose cohorts greater than or equal to 0.7 mg (Cmax, insulin)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (Tmax, insulin)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (AUCinsulin,0-60 min)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (AUCinsulin,0-240 min)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (Cmax, glucagon)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (Tmax, glucagon)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (AUCglucagon,0-60 min)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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, for dose cohorts greater than or equal to 0.7 mg (AUCglucagon,0-240 min)
  • Time Frame: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 and Day 5
  • 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

Participating in This Clinical Trial

Inclusion Criteria

• Healthy male subject – Body Mass Index (BMI) between 21.0 and 29.9 kg/m^2, both inclusive – Body weight of at least 70.0 kg – Glycosylated hemoglobin A1c (HbA1c) less than 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 < 90 mmHg or >139 mmHg and/or diastolic blood pressure less than 50 mmHg or greater than 89 mmHg – Symptoms of arterial hypotension – Further exclusion criteria apply

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • Zealand Pharma
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Zealand Pharma A/S, Study Director, Zealand Pharma A/S