Evaluation of the Safety, Tolerability and Bioavailability of Dasiglucagon Following Subcutaneous (SC) Compared to IV Administration

NCT03735225 | Completed Phase 1

• 1 other identifier: ZP4207-17144
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the trial is to characterize the safety and tolerability of dasiglucagon 4 mg/mL following IV administration at increasing doses in healthy volunteers. One cohort of subjects will receive a SC dose of dasiglucagon to characterize the bioavailability of dasiglucagon following SC administration compared to IV administration. Furthermore, the trial aims to assess the potential effect of dasiglucagon on corrected QT interval (QTc) prolongation via a concentrationresponse analysis.

Conditions

Hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Change measures from baseline considering nausea, vomiting and diarrhea

  day 1, day 2, day 28

Secondary Outcomes (9)

• Clinical assessment of local tolerability at injection site by physical examination

  day-1, day 1, day 2, day 28

• Occurrence of anti-drug antibodies (ADA)

  day 1 and day 28

• Plasma dasiglucagon profiles following IV administration, Area Under the Curve (AUC)

  Pre-dose, 5, 15, 25, 40, 60, 80, 100, 120, 140, 180 and 240 min.

• Plasma dasiglucagon profiles following SC administration, Area Under the Curve (AUC)

  Pre-dose, 5, 15, 25, 35, 45, 60, 90, 130, 210 and 300 min.

• Change-from-baseline in ECG for QTcF

  From day -1 to day 2 and day 28

Study Arms (3)

IV Dasiglucagon

EXPERIMENTAL

Dasiglucagon 0.1, 0.3, 0.6, 1.5 or 2.0 mg administered IV as a single dose

Drug: Dasiglucagon

SC 0.6 mg Dasiglucagon

EXPERIMENTAL

Dasiglucagon 0.6 mg administered SC as a single dose

Drug: Dasiglucagon

IV Placebo

PLACEBO COMPARATOR

Placebo 0.1, 0.3, 0.6, 1.5 or 2.0 mg administered IV as a single dose

Drug: Placebo

Interventions

Dasiglucagon DRUG

Dasiglucagon injection

Also known as: ZP4207

IV Dasiglucagon; SC 0.6 mg Dasiglucagon

Placebo DRUG

Placebo for Dasiglucagon injection

Also known as: Placebo for Dasiglucagon

IV Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 subject).
• Healthy female or male subjects aged between 18 and 45 years, both inclusive.
• Body weight between 60 and 90 kg, both inclusive.
• Subjects in good health according to age (medical history, physical examination, vital signs, and laboratory assessments), as judged by the investigator.
• Systolic Blood Pressure (SBP) ≥90 mmHg, ≤140 mmHg and Diastolic Blood Pressure (DBP) ≤90 mmHg measured after at least 5 min rest in supine position.
• A pulse rate of ≥50 and ≤90 b/min measured after at least 5 min rest in supine position.
• lead ECG with QTcF \< 450 ms, PR \< 220 ms and QRS \< 110 ms.
• A female subject must meet one of the following criteria:
• Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens throughout the entire duration of the trial from screening until the last follow-up visit. An acceptable method of contraception includes one of the following:
• Total heterosexual sexual abstinence can be used as a method of contraception if this is the participant's preferred lifestyle and the method is established. Periodic sexual abstinence is not an acceptable method of contraception
• Single method (use only one method):
• intrauterine device (IUD),
• hormone rod inserted under the skin,
• male partner's sterilization
• Double method:

You may not qualify if:

• Previous participation in any trial with dasiglucagon. Participation defined as enrolled into trial.
• Known or suspected hypersensitivity to trial product(s) or related products.
• History of severe hypersensitivity to medicines or foods or history of severe medicinal/food induced anaphylactic reaction.
• Receipt of any investigational product within 3 months prior to screening.
• Females who are pregnant according to a positive pregnancy test, are actively attempting to get pregnant, or are lactating.
• Any history or presence of cancer, except adequately treated (as judged by investigator) basal or squamous cell skin cancer or cervical carcinoma in situ.
• A history or presence of any clinically significant respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, hematological, dermatological, venereal, neurological or psychiatric diseases, or other major diseases at the discretion of the investigator.
• Known cardiovascular disease, arthrosclerosis, angina pectoris, or a history of myocardial infarction or coronary arterial bypass graft/percutaneous coronary intervention.
• Clinically significant illness (eg, systemic infection) within 4 weeks before screening, as judged by the investigator.
• Any significant pre-existing medical condition as well as pre-planned procedures or surgeries.
• Positive results for Hepatitis B antigens, Hepatitis C antibodies and/or human immunodeficiency virus (HIV) 1 antigen or HIV1/2 antibodies, at screening.
• Any clinically significant abnormal hematology, biochemistry, or urinalysis screening tests, as judged by the investigator.
• Any of the following abnormal laboratory parameters at screening:
• alanine aminotransferase (ALT) \> upper limit of normal \[ULN\] + 10%, aspartate aminotransferase (AST) \> ULN + 10%,
• Bilirubin \> ULN + 20%

Sponsors & Collaborators

• Zealand Pharma: lead

Study Sites (1)

CRS Clinical Research Services Mannheim GmbH

Mannheim, 68167, Germany

Location

Related Publications (1)

• Tehranchi R, Pettersson J, Melgaard AE, Seitz F, Valeur A, Maarbjerg SJ. Dasiglucagon Effects on QTc in Healthy Volunteers: A Randomized, Placebo-Controlled, Dose-Escalation, Double-Blind Study. Curr Ther Res Clin Exp. 2022 Mar 29;96:100668. doi: 10.1016/j.curtheres.2022.100668. eCollection 2022.

  PMID: 35464292 DERIVED

MeSH Terms

Conditions

Hypoglycemia

Interventions

dasiglucagon

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Christina M Sylvest, MSc Pharm

  Zealand Pharma A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: November 8, 2018
• Study Start: November 7, 2018
• Primary Completion: June 24, 2019
• Study Completion: June 24, 2019
• Last Updated: March 23, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)