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The trial is a single-centre, randomized, double-blind, parallel trial in Group 1 and cross-over trial in Groups 2-4 with single doses of ZP4207 administered s.c. to hypoglycemic Type 1 diabetic patients to evaluate the pharmacokinetics and pharmacodynamics of ZP4207 as compared to marketed glucagon.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ZP4207 | Experimental | ZP4207 (peptide analogue of human glucagon) Planned doses: 0.1, 0.3, 0.6, 1.0 mg s.c. |
|
| GlucaGen | Active Comparator | GlucaGen (native glucagon) Planned doses: 0.5, 1.0 mg s.c. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZP4207 | Drug | Parallel trial in Group 1 and cross-over trial in Groups 2-4 with single doses of ZP4207 administered s.c. to hypoglycemic Type 1 diabetic patients |
|
| Measure | Description | Time Frame |
|---|---|---|
| PD endpoint: Plasma glucose profiles 0-360 min above baseline (Area under the effect curve 0-360 min) | At visit 2 and 3 | During visit 2 and 3 (0-360min) |
| PD endpoint: Time to peak plasma glucose concentration (tmax) | At visit 2 and 3 | During visit 2 and 3 (0-360min) |
| PK endpoint: Plasma ZP4207 and glucagon profiles 0-360 min | At visit 2 and 3 | During visit 2 and 3 (0-360min) |
| PK endpoint: Peak plasma concentration (Cmax) | At visit 2 and 3 | During visit 2 and 3 (0-360min) |
| PK endpoint: Time to peak plasma concentration (tCmax) | At visit 2 and 3 | During visit 2 and 3 (0-360min) |
| Measure | Description | Time Frame |
|---|---|---|
| PD endpoints: Percentage of patients achieving a plasma glucose concentration ≥70 mg/dL within 30 minutes after treatment | At visit 2 and 3 | During visit 2 and 3 (0-30min) |
| PD endpoints: Time to plasma glucose concentration of ≥70 mg/dL |
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Inclusion Criteria:
Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the patient).
Male and female patients with T1D for at least one year, as defined by the American Diabetes Association.
Having been treated with insulin for T1D for at least 1 year.
Stable disease with HbA1c < 8.5%.
Expected stable insulin treatment during participation in trial and 3 month prior to the screening visit.
Age between 18 and 50 years, both inclusive.
Body weight between 60 and 90 kg, both inclusive.
Patients in good health according to age (medical history, physical examination, vital signs, ECG, lab assessments), as judged by the Investigator.
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Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ulrike Hövelmann, MD | Profil Institut für Stoffwechselforschung GmbH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Profil Institut für Stoffwechselforschung GmbH | Neuss | 41460 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29273578 | Derived | Hovelmann U, Bysted BV, Mouritzen U, Macchi F, Lamers D, Kronshage B, Moller DV, Heise T. Pharmacokinetic and Pharmacodynamic Characteristics of Dasiglucagon, a Novel Soluble and Stable Glucagon Analog. Diabetes Care. 2018 Mar;41(3):531-537. doi: 10.2337/dc17-1402. Epub 2017 Dec 22. |
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| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| D005934 | Glucagon |
| ID | Term |
|---|---|
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
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|
| GlucaGen | Drug | Parallel trial in Group 1 and cross-over trial in Groups 2-4 with single doses of GlucaGen administered s.c. to hypoglycemic Type 1 diabetic patients |
|
|
At visit 2 and 3
| During visit 2 and 3 (0-360min) |
| PD endpoints: Percentage of patients achieving a plasma glucose increase of ≥20 mg/dL within 30 minutes after treatment | At visit 2 and 3, | During visit 2 and 3 (0-30min) |
| PD endpoints: Time to plasma glucose increase of ≥20 mg/dL | At visit 2 and 3, | During visit 2 and 3 (0-360min) |
| PK endpoints: Baseline adjusted glucagon profiles 0-360 min | At visit 2 and 3, | During visit 2 and 3 (0-360min) |
| PK endpoints: AUC0-inf for plasma ZP4207 concentration | At visit 2 and 3, Area under the plasma curve from 0 to infinity | During visit 2 and 3 (0-360min) |
| Exploratory endpoint: Insulin concentrations | At visit 2 and 3, insulin concentrations in serum | During visit 2 and 3 (0-360min) |
| Exploratory endpoint: Changes in hypoglycaemic symptom scores from 0-30 minutes | At visit 2 and 3 | During visit 2 and 3 (0-30min) |
| Safety and Tolerability: Number of participants with adverse events | Number of participants with adverse events | Through study completion (up to 63 days) |
| Safety and Tolerability: Changes or findings from baseline in physical examination | An examination of the following body systems will be performed:
| Through study completion (up to 63 days) |
| Safety and Tolerability: Changes or findings from baseline (normal ranges) in clinical safety laboratory parameters | Haematology biochemistry, and urinalysis | Through study completion (up to 63 days) |
| Safety and Tolerability: Changes or findings from baseline in vital signs | systolic/diastolic blood pressure (mmHg) and heart rate (beats per minute), body temperature (°C), respiratory frequency (RF/min) | Through study completion (up to 63 days) |
| Safety and Tolerability: Changes or findings from baseline in ECG | Heart rate, PQ, QRS, QT, QTcB | Through study completion (up to 63 days) |
| Safety and Tolerability: Local tolerability of injection site | Findings in local tolerability by means of the following assessments.
| Through study completion (up to 63 days) |
| Safety and Tolerability: Immunogenicity (Ant-Drug Antibody sampling) | Antidrug antibodies incidences | Through study completion (up to 63 days) |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |