A Phase 3, Randomized, Double-blind, Parallel Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in Rescue Treatment of Hypoglycemia in Subjects With Type 1 Diabetes Mellitus Compared to Placebo and With Reference to GlucaGen
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 170
- 试验地点
- 4
- 主要终点
- Time to Plasma Glucose Recovery
研究概览
简要总结
The objective of the trial is to demonstrate superiority of dasiglucagon compared to placebo following a single subcutaneous dose administered to subjects with type 1 diabetes mellitus (T1DM) with insulin-induced hypoglycemia. Additionally to compare the glycemic response observed after administration dasiglucagon with that of GlucaGen®.
详细描述
This was a global, multicenter, randomized, parallel, and double-blind clinical trial confirming the efficacy and safety of dasiglucagon for insulin-induced hypoglycemia in patients with T1DM. The patients were randomized 2:1:1 to receive a single subcutaneous 0.6 mg dose of dasiglucagon, placebo, or a 1 mg dose of GlucaGen and followed for at least 28 days after receiving treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male subjects with type 1 diabetes mellitus (T1DM) for at least 1 year, diagnostic criteria as defined by the American Diabetes Association
- •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
- •Hemoglobin A1c <10%
排除标准
- •Previously treated with dasiglucagon (previously referred to as ZP4207)
- •Known or suspected allergy to trial product(s) or related products
- •Females who are pregnant according to a positive pregnancy test, are actively attempting to get pregnant, or are lactating.
- •History of hypoglycemic events associated with seizures in the last year prior to screening
- •History of severe hypoglycemia in the last month prior to screening
- •Active malignancy within the last 5 years
- •Current bleeding disorder, including anti-coagulant treatment
- •Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor)
- •Use of a daily systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial
- •Clinically significant abnormal ECG at screening as judged by the investigator
- •Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening
- •Surgery or trauma with significant blood loss within the last 2 months prior to screening
- •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
研究组 & 干预措施
Dasiglucagon
Single fixed dose (s.c.injection) of dasiglucagon
干预措施: Dasiglucagon (Drug)
Placebo
Single fixed dose (s.c.injection) of placebo
干预措施: Placebo (Drug)
GlucaGen®
Single fixed dose (s.c.injection) of GlucaGen®
干预措施: GlucaGen (Drug)
结局指标
主要结局
Time to Plasma Glucose Recovery
时间窗: 0-45 minutes after dosing
Plasma glucose recovery is defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose. The outcome measure used a Kaplan-Meier estimate with 95% confidence interval. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.
次要结局
- Plasma Glucose Recovery(0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection)
- Plasma Glucose Changes From Baseline(0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection)
- Time to Target(0-45 minutes after dosing)
- Pharmacodynamics - Area Under the Effect Curve(0-30 minutes after dosing)
- Pharmacokinetics - Area Under the Plasma Concentration Curve(0-120 minutes after dosing)
- Immunogenicity - Occurence of Anti-drug Antibodies(28 days)
- Pharmacokinetics - Maximum Plasma Concentration(0-120 minutes after dosing)
- Pharmacokinetics - Time to Maximum Plasma Concentration(0-120 minutes after dosing)
- Rescue Infusion of IV Glucose During the Hypoglycemic Clamp Procedure(0-45 minutes after dosing)
- Time to First Rescue Infusion of IV Glucose(0-45 minutes after dosing)