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

Zealand Pharma1 site in 1 country68 target enrollmentNovember 7, 2022

ConditionsOverweight Healthy Volunteers Obese

InterventionsZP8396

DrugsZP8396 Drug: Placebo (ZP8396)

Overview

Phase: Phase 1
Intervention: ZP8396
Conditions: Overweight
Sponsor: Zealand Pharma
Enrollment: 68
Locations: 1
Primary Endpoint: Incidence of treatment emergent adverse events (TEAEs)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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

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.

Registry

clinicaltrials.gov

Start Date

November 7, 2022

End Date

June 13, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Zealand Pharma

Responsible Party

Sponsor

Eligibility Criteria

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
•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

•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
•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

Arms & Interventions

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.

Intervention: ZP8396

Outcomes

Primary Outcomes

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

Pharmacokinetics (PK) of ZP8396 (AUCinf)(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)(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)(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)
Accumulation Ratio for Cmax(Part 1: Day 1 (pre-dose) to Day 92)
Pharmacodynamics (PD) of ZP8396 (Cmax 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])(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)(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)(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, insulin)(Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40)
Pharmacokinetics (PK) of ZP8396 (Cmax)(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)(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)(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)
Accumulation Ratio for AUCτ(Part 1: Day 1 (pre-dose) to Day 92)
Pharmacodynamics (PD) of ZP8396 (Tmax 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)(Part 1: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40)
Pharmacokinetics (PK) of ZP8396 (AUClast)(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)(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 (AUCτ)(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)(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 (Tmax, Plasma Glucose [PG])(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)(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)(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, insulin)(Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40)
Pharmacodynamics (PD) of ZP8396 (AUEglucagon,0-60 minutes)(Part 1: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40)
Pharmacodynamics (PD) of ZP8396 (AUEinsulin,0-240 min)(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)(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)(Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40)
Pharmacodynamics (PD) of ZP8396 (AUEglucagon,0-240 minutes)(Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40)