ZP4207(Dasiglucagon) Administered to T1D Patients to Assess the PK and PD Compared to Marketed Glucagon

NCT02916251 | Completed Phase 2

• 1 other identifier: ZP4207-16098
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The trial is a single-centre, randomised, sequential, cross-over trial assessing pharmacokinetic and pharmacodynamic responses after micro-doses of ZP4207 (dasiglucagon\*) administered subcutaneously to patients with type 1 diabetes mellitus under euglycaemic and hypoglycaemic conditions and compared to marketed glucagon. \*dasiglucagon is the proposed International Nonproprietary Name (pINN) for ZP4207

Conditions

Diabetes Mellitus Type 1

Outcome Measures

Primary Outcomes (6)

• PK endpoint for ZP4207(dasiglucagon) and baseline adjusted glucagon: AUC 0-240 min

  Area under the curve from 0-240 min

  AUC 0-240 min during all treatment periods (V2-V5)

• PK endpoint for ZP4207(dasiglucagon) and baseline adjusted glucagon: Cmax

  max. concentration

  Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Peak of plasma concentration during all treatment periods (V2-V 5)

• PK endpoint for ZP4207(dasiglucagon) and baseline adjusted glucagon: tmax

  Time to peak plasma concentration

  Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Time to peak plasma concentration during all treatment periods (V2-V5)

• PD endpoint: Plasma glucose profiles above baseline: AUE 0-240 min

  Area under the effect curve from 0-240 min

  Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing. AUE 0-240 min during all treatment periods (V2-V5)

• PD endpoint: Plasma glucose profiles above baseline: CEmax

  Max concentration effect

  Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing. Peak of plasma glucose concentration during all treatment periods (V2-V5)

• PD endpoint: Plasma glucose profiles above baseline: tmax

  Time to peak plasma glucose concentration

  Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing Time to plasma glucose concentration during all treatment periods (V2-V5)

Secondary Outcomes (23)

• PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: MRT

  Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Mean residence time for ZP4207(dasiglucagon) and baseline adjusted glucagon during all treatment periods (V2-V5)

• PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: Vz/f,

  Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Volume of distribution of plasma ZP4207(dasiglucagon) or glucagon during all treatment periods (V2-V5)

• PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: λz

  Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Terminal elimination rate constant of ZP4207(dasiglucagon) and baseline adjusted glucagon during all treatment periods (V2-V5)

• PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: t½,

  Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Terminal plasma elimination half-life of ZP4207(dasiglucagon) or glucagon during all treatment periods (V2-V5)

• PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: CL/f

  Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Total body clearance of plasma ZP4207(dasiglucagon) or glucagon during all treatment periods (V2-V5)

Study Arms (2)

ZP4207(dasiglucagon)

EXPERIMENTAL

Intervention: ZP4207(dasiglucagon) glucagon analogue (4 mg/mL) planned doses: 0.03, 0.08, 0.2 and 0.6 mg at euglycemic and hypoglycemic conditions.

Drug: ZP4207(dasiglucagon) glucagon analogue

Glucagon (Native glucagon)

ACTIVE COMPARATOR

Intervention: Glucagon (Native glucagon) 1 mg/mL as active comparator planned doses: 0.03, 0.08 and 0.2 mg at euglycemic conditions.

Drug: Glucagon (Native glucagon)

Interventions

ZP4207(dasiglucagon) glucagon analogue DRUG

Cross-over design with single s.c. administration in euglycemic and hypoglycemic T1D

Also known as: dasiglucagon

ZP4207(dasiglucagon)

Glucagon (Native glucagon) DRUG

Cross-over design with single s.c. administration in euglycemic T1D

Also known as: Lilly Glucagon

Glucagon (Native glucagon)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• To be included in the trial, patients have to fulfil all of the following criteria:
• Signed and dated informed consent obtained before any trial-related activities. (Trial-related activities are any procedures that would not have been performed during normal management of the patient).
• Male and female patients with T1DM for at least 1 year, as defined by the American Diabetes Association1.
• Age between 18 and 64 years, both inclusive.
• HbA1c \< 8.5%.
• C-peptide negative defined as below the lower limit of quantification.
• Stable insulin regimen via an insulin infusion pump for at least 1 month prior to screening.
• Weight between 60 kg and 90 kg, both inclusive.
• Patients in good health according to age (medical history, physical examination, vital signs, 12-lead ECGs, lab assessments), as judged by the Investigator.-

You may not qualify if:

• Patients meeting any of the following criteria during screening evaluations will be excluded from trial participation:
• Unable to provide informed consent (e.g., impaired cognition or judgement).
• Patients with mental incapacity or language barriers which preclude adequate understanding or cooperation, who are unwilling to participate in the trial, or who in the opinion of the Investigator should not participate in the trial.
• Receipt of any medicinal product in clinical development within 3 months prior screening.
• Previous exposure to ZP4207(dasiglucagon) or previously randomized to this trial.
• Known or suspected allergy to trial product(s) or related products.
• History of adverse reaction to glucagon (including allergy) besides nausea and vomiting.
• History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
• New onset clinically significant illness within 4 weeks prior to screening, as judged by the Investigator.
• History of liver disease that is expected to interfere with the anti-hypoglycemia action of glucagon (e.g., liver failure or cirrhosis). Other liver disease (i.e., active hepatitis, steatosis, active biliary disease, any tumor of the liver, hemochromatosis, glycogen storage disease) may exclude the patient if it causes significant compromise to liver function or may do so in an unpredictable fashion.
• Any history or presence of clinically relevant cardiovascular, pulmonary, respiratory, gastrointestinal, renal, metabolic, endocrinological (with the exception of conditions associated with diabetes mellitus), haematological, dermatological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynaecologic (if female), or infectious disease, or signs of acute illness as judged by the Investigator.
• Clinically significant abnormal haematology, biochemistry or urinalysis screening tests, as judged by the Investigator. In particular, elevated liver enzymes (AST or ALT \> 2 times the upper limit of normal, or bilirubin \>1.5 the upper limit of normal) or impaired renal function (elevated serum creatinine values above the upper limit of normal).
• Hypertension with systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg (excluding white-coat hypertension; therefore, if a repeated measurement shows values within the range, the patient can be included in the trial); a heart rate at rest outside the range of 50-90 beats per minute.
• Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the Investigator.
• Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.

Sponsors & Collaborators

• Zealand Pharma: lead

Study Sites (1)

Profil Institut für Stoffwechselforschung GmbH

Neuss, North Rhine-Westphalia, 41460, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

dasiglucagon; Glucagon

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Hövelmann Ulrike, MD

  Profil Neuss GmbH Neuss, Germany, 41460

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: September 27, 2016
• Study Start: December 1, 2016
• Primary Completion: April 5, 2017
• Study Completion: April 5, 2017
• Last Updated: April 21, 2017

Record last verified: 2017-04

Locations

DE (1)