A phase 3b, randomized, double-blind, crossover trial to compare the efficacy and safety of 2 different batches of subcutaneous dasiglucagon in patients with type 1 diabetes mellitus
- Conditions
- Type 1 Diabetes mellitusMedDRA version: 20.0Level: PTClassification code 10067584Term: Type 1 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-003834-34-AT
- Lead Sponsor
- Zealand Pharma A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 92
Patients will be eligible to be included in the trial only if all of the following criteria apply:
1. 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)
2. Female or male patients with T1DM for at least 1 year, diagnostic criteria as defined by the American Diabetes Association (American Diabetes Association, 2017)
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 <10.0% at screening
5. Age between 18 and 75 years, both inclusive, at screening
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 (only acceptable if corresponding to the preferred and usual lifestyle of the subject)
ii. Systemic contraceptives (birth control pills, injectable/implant/ insertable hormonal birth control products, transdermal patch)
iii. Intrauterine device (with and without hormones)
iv. Condom with spermicide
[Germany only: An acceptable method of contraception includes one of the following:
I. 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
II. Single method (use only one method):
• Intrauterine device (IUD)
• Hormone rod inserted under the skin
• Male partner's sterilization
III. Double method:
• Hormone contraception A) estrogen and/or progesterone oral contraceptives, B) transdermal patch, C) vaginal ring, D) injection
• In combination with one of the following: a) vaginal cap with spermicide, b) vaginal sponge (only for women who have never given birth), c) condom, d) female condom ]
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 77
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11
Patients are excluded from the trial if any of the following criteria apply:
1. Previous participation in a clinical trial within the dasiglucagon program
2. Known or suspected allergy to trial medication(s) or related products
3. History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema)
4. Previous participation in this trial. Participation is defined as having been randomized
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 or hypoglycemia unawareness in the last year prior to screening
7. Current daily basal insulin treatment > 1.0 U/kg/day
8. History of epilepsy or seizure disorder
9. History of severe hypoglycemia (an episode requiring assistance from another person) in the last month prior to screening
10. Receipt of any investigational medicinal product within 3 months prior to screening
11. Active malignancy within the last 5 years
12. Congestive heart failure, New York Heart Association class II-IV
13. Inadequately treated blood pressure as defined as systolic blood pressure =160 mmHg or diastolic blood pressure =90 mmHg at screening (The Task Force for the management of arterial hypertension, 2013)
14. Current bleeding disorder, including use of anticoagulant treatment
15. Known presence or history of pheochromocytoma (i.e., adrenal gland tumor) or insulinoma (i.e., insulin-secreting pancreas tumor)
16. Use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs at screening
17. Any of the following abnormal laboratory parameters at screening:
? Aspartate aminotransferase >2.5 × the upper limit of normal
? Alanine aminotransferase >2.5 × the upper limit of normal
? Bilirubin >1.5 × the upper limit of normal
? Estimated glomerular filtration rate <30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease Study definition (Levey et al, 2006)
? Altered electrolyte values of clinical relevance for cardiac conduction, as judged by the investigator
18. Clinically significant abnormal electrocardiogram (ECG) at screening as evaluated by investigator
19. Clinically significant illness within 4 weeks before screening, as judged by the investigator
20. Any donation of blood or plasma in the past month, or donation in excess of 500 mL within 12 weeks before screening
21. Surgery or trauma with significant blood loss within the last 2 months before screening
22. A positive result in the alcohol and/or urine drug screen at the screening visit
23. Significant history of alcoholism or non-prescribed opioid misuse as judged by the investigator
24. Patients with mental incapacity or language barriers that 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
25. Any condition interfering with trial participation or evaluation or that could be hazardous to the patient
26. 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: The primary objective is to show non-inferiority of the efficacy of a single subcutaneous dose of dasiglucagon batch B relative to that of dasiglucagon batch A for treatment of hypoglycemia in patients with type 1 diabetes mellitus;Secondary Objective: The secondary objective is to evaluate the safety, immunogenicity and PK of 2 different batches of dasiglucagon following a single SC dose administered to patients with T1DM with insulin-induced hypoglycemia;Primary end point(s): Time to plasma glucose recovery. ;Timepoint(s) of evaluation of this end point: 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 intravenous (IV) glucose.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Plasma glucose change from baseline at 30 minutes, at 20 minutes, at 15 minutes, and at 10 minutes after trial product injection or at the time of rescue;Timepoint(s) of evaluation of this end point: From baseline at 30 minutes, at 20 minutes, at 15 minutes, and at 10 minutes after trial product injection or at the time of rescue.