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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ZP8396 | Experimental | 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. |
|
| Placebo (ZP8396) | Placebo Comparator | Part 1: In each of the 2 dose cohorts, 3 subjects will receive placebo. Part 2: In each of the 3 cohorts, 4 subjects will receive placebo. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) of ZP8396 (AUCτ) | 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 |
| Pharmacokinetics (PK) of ZP8396 (AUCinf) |
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Inclusion Criteria:
Part 1:
Further inclusion criteria apply
Part 2:
Further inclusion criteria apply
Exclusion Criteria:
Part 1:
Further exclusion criteria apply
Part 2:
Further exclusion criteria apply
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| Name | Affiliation | Role |
|---|---|---|
| Zealand Pharma A/S | Zealand Pharma A/S | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Profil Institut für Stoffwechselforschung GmbH | Neuss | North Rhine-Westphalia | 41460 | Germany |
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| ID | Term |
|---|---|
| D050177 | Overweight |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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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.
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|
| 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). |
|
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 |
| 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 |
| 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 |
| 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 |
| Pharmacokinetics (PK) of ZP8396 (λz) | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Accumulation Ratio for AUCτ | Accumulation Ratio for AUCτ | Part 1: Day 1 (pre-dose) to Day 92 |
| Accumulation Ratio for Cmax | Accumulation Ratio for Cmax | Part 1: Day 1 (pre-dose) to Day 92 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |