A study to confirm efficacy and safety of dasiglucagon to rescue treatment of hypoglycemia in subjects with type 1 diabetes mellitus (T1DM) compared to placebo and with reference to GlucaGen®

Phase 1

Conditions: Type 1 diabetes mellitus
MedDRA version: 20.0Level: SOCClassification code 10027433Term: Metabolism and nutrition disordersSystem Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2017-002449-31-AT

Lead Sponsor: Zealand Pharma A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 176

Inclusion Criteria

Subjects will be entered into this trial only if they meet all of the following criteria:
1. 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 subject).
2. Female or male subjects with T1DM for at least 1 year, diagnostic criteria as defined by the American Diabetes Association (3).
3. Treated with insulin for T1DM for at least 1 year and with stable insulin treatment (defined as no more than a 10-unit daily variation in total daily insulin dose) 30 days prior to screening
4. Hemoglobin A1c <10%.
5. Aged between 18 and 75 years, both inclusive.
6. A female subject must meet one of the following criteria:
a. Participant is of childbearing potential and agrees to use one of the
accepted contraceptive regimens throughout the entire duration of the trial from screening and until last follow-up visit. An acceptable method of contraception includes one of the following:
i. Abstinence from heterosexual intercourse;
ii. Systemic contraceptives (birth control pills, injectable/implant/
insertable hormonal birth control products, transdermal patch); iii. Intrauterine device (with and without hormones); or
iv. Condom with spermicide; or
b. Participant is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation), or in a menopausal state (at least 1 year without menses).
7. A male subject must meet the following criteria: Surgically sterilized or willing to refrain from sexual intercourse from screening and until last follow-up visit or, if sexually active, uses condom and partner practices contraception during the trial from screening and until last follow-up visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 156
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

Subjects meeting any of the following criteria during screening evaluations will be excluded from trial participation:
1. Previously treated with dasiglucagon (previously referred to as ZP4207).
2. Known or suspected allergy to trial product(s) or related products.
3. History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema).
4. Previous participation (randomization) in this trial.
5. Females who are pregnant according to a positive pregnancy test, are actively attempting to get pregnant, or are lactating.
6. History of hypoglycemic events associated with seizures in the last year prior to screening.
7. History of severe hypoglycemia (defined as plasma glucose <54 mg/dL [3.0 mmol/L]) in the last month prior to screening.
8. Receipt of any investigational drug within 3 months prior to screening.
9. Active malignancy within the last 5 years.
10. Congestive heart failure, New York Heart Association class II-IV.
11. Inadequately treated blood pressure, defined as systolic =160 mmHg or diastolic =90 mmHg) at screening (15)
12. Current bleeding disorder, including anti-coagulant treatment.
13. Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor).
14. Use of a daily systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial.
15. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × the upper limit of the normal range (ULN), bilirubin >1.5 × ULN, estimated glomerular filtration rate <30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease study definition (16), or altered electrolyte values of clinical relevance for cardiac conduction, as judged by the investigator.
16. Clinically significant abnormal ECG at screening as judged by the investigator.
17. Clinically significant illness within 4 weeks before screening, as judged by the investigator.
18. Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening.
19. Surgery or trauma with significant blood loss within the last 2 months prior to screening.
20. A positive result in the alcohol and/or urine drug screen at the screening visit. Significant history of alcoholism or drug abuse as judged by the investigator or consuming more than 24 g alcohol per day for men, or more than 12 g alcohol per day for women.
21. Subjects 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.
22. Any condition interfering with trial participation or evaluation or that could be hazardous to the subject.
23. The use of prescription or non-prescription medications known to cause QT prolongation.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: <br>The primary objective is to demonstrate superiority of dasiglucagon compared to placebo following a single subcutaneous 0.6 mg dose administered to subjects with type 1 diabetes mellitus with insulin-induced hypoglycemia.;Secondary Objective: The secondary objective is to compare the glycemic response observed after dasiglucagon with that of GlucaGen.;Primary end point(s): Time to plasma glucose recovery. Plasma glucose recovery is defined as first increase in plasma glucose of =20 mg/dL (1.1 mmol/L) from baseline during the hypoglycemic clamp procedure without administration of rescue IV glucose.;Timepoint(s) of evaluation of this end point: The plasma glucose profile for evaluation of the primary and secondary clinical efficacy endpoints will be assessed based on plasma concentration data (AUC0-30min) from samples collected at the dosing visit (Visit 2). Samples will be collected pre-dose, and at 4, 6, 8, 10, 12, 15, 17, 20, 25, 30, 40, 50, 60, 75, and 90 minutes after dosing

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key Secondary end point:<br><br>1. Plasma glucose recovery within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after study drug injection without administration of rescue IV glucose.<br>2.Plasma glucose changes from baseline within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after study drug injection or at the time of rescue.;Timepoint(s) of evaluation of this end point: The plasma glucose profile for evaluation of the primary and secondary clinical efficacy endpoints will be assessed based on plasma concentration data (AUC0-30min) from samples collected at the dosing visit (Visit 2). Samples will be collected pre-dose, and at 4, 6, 8, 10, 12, 15, 17, 20, 25, 30, 40, 50, 60, 75, and 90 minutes after dosing

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