Clinical trial NCT05613387: A Research Study Looking at the Safety of Multiple Doses of ZP8396 and How it Works in the Body of Healthy Participants
Official title: A Randomized, Multiple Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZP8396 Administered to Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Overweight
Healthy Volunteers
Obese
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
First posted: 2022-11-14
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1: A single-centre, placebo-controlled, double-blind (within cohorts), randomised multiple ascending dose trial.

Part 2: A single-centre, placebo-controlled, double-blind (within cohorts), randomised multiple ascending dose trial, using dose up-titration.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment emergent adverse events (TEAEs)
timeFrame: 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 outcomes:
measure: Pharmacokinetics (PK) of ZP8396 (AUCτ)
timeFrame: 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
measure: Pharmacokinetics (PK) of ZP8396 (AUCinf)
timeFrame: 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
measure: Pharmacokinetics (PK) of ZP8396 (AUClast)
timeFrame: 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
measure: Pharmacokinetics (PK) of ZP8396 (Cmax)
timeFrame: 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
measure: Pharmacokinetics (PK) of ZP8396 (tmax)
timeFrame: 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
measure: Pharmacokinetics (PK) of ZP8396 (λz)
timeFrame: 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
measure: Pharmacokinetics (PK) of ZP8396 (t½)
timeFrame: 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
measure: Pharmacokinetics (PK) of ZP8396 (Vz/f)
timeFrame: 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
measure: Pharmacokinetics (PK) of ZP8396 (CL/f)
timeFrame: 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
measure: Pharmacokinetics (PK) of ZP8396 (Ctrough)
timeFrame: 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
measure: Accumulation Ratio for AUCτ
timeFrame: Part 1: Day 1 (pre-dose) to Day 92
measure: Accumulation Ratio for Cmax
timeFrame: Part 1: Day 1 (pre-dose) to Day 92
measure: Pharmacodynamics (PD) of ZP8396 (Cmax acetaminophen)
timeFrame: 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
measure: Pharmacodynamics (PD) of ZP8396 (Tmax acetaminophen)
timeFrame: 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
measure: Pharmacodynamics (PD) of ZP8396 (AUCacetaminophen, 0-60 min)
timeFrame: 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
measure: Pharmacodynamics (PD) of ZP8396 (AUCacetaminophen, 0-240 min)
timeFrame: 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
measure: Pharmacodynamics (PD) of ZP8396 (Emax, Plasma Glucose [PG])
timeFrame: 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
measure: Pharmacodynamics (PD) of ZP8396 (Tmax, Plasma Glucose [PG])
timeFrame: 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
measure: Pharmacodynamics (PD) of ZP8396 (AUE, Plasma Glucose [PG], 0-60 minutes)
timeFrame: 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
measure: Pharmacodynamics (PD) of ZP8396 (AUE, Plasma Glucose [PG], 0-240 minutes)
timeFrame: 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
measure: Pharmacodynamics (PD) of ZP8396 (Emax, insulin)
timeFrame: Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
measure: Pharmacodynamics (PD) of ZP8396 (Tmax, insulin)
timeFrame: Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
measure: Pharmacodynamics (PD) of ZP8396 (AUEinsulin,0-60 minutes)
timeFrame: Part 1: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
measure: Pharmacodynamics (PD) of ZP8396 (AUEinsulin,0-240 min)
timeFrame: Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
measure: Pharmacodynamics (PD) of ZP8396 (Emax, glucagon)
timeFrame: Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
measure: Pharmacodynamics (PD) of ZP8396 (Tmax, glucagon)
timeFrame: Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
measure: Pharmacodynamics (PD) of ZP8396 (AUEglucagon,0-60 minutes)
timeFrame: Part 1: 0-60 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
measure: Pharmacodynamics (PD) of ZP8396 (AUEglucagon,0-240 minutes)
timeFrame: Part 1: 0-240 minutes, relative to ingestion of MTM/acetaminophen on Day -1 (baseline), Day 5 and Day 40
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
state: North Rhine-Westphalia
Study officials:
affiliation: Zealand Pharma A/S
name: Zealand Pharma A/S
role: STUDY_DIRECTOR
References: