G-Pen (Glucagon Injection) Compared to GlucaGen® Hypokit® (Glucagon) for Induced Hypoglycemia Rescue in Adults With T1D: A Phase 3 Multi-center, Randomized, Controlled, Single Blind, 2-way Crossover Study to Evaluate Efficacy and Safety
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 132
- 试验地点
- 7
- 主要终点
- Severe Hypoglycemia Rescue
研究概览
简要总结
This is a multi-center, randomized, controlled, single-blind, two-way crossover efficacy and safety study in subjects with Type 1 diabetes mellitus. The study involves two daytime clinical research center (CRC) visits with random assignment to receive G-Pen glucagon 1 mg during one period and Novo Glucagon 1 mg during the other. Each daytime visit is preceded by an overnight stay in the CRC. In the morning of the inpatient study visit, the subject is brought into a state of severe hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose < 54 mg/dL (3 mmol/L) is verified, the subject is administered a dose of G-Pen or Novo Glucagon via subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes post-dosing, with a value of >70.0 mg/dL (3.89 mmol/L) or an increase of > 20 mg/dL (>1.11 mmol/L) within 30 minutes of glucagon administration indicating a positive response. After 3 hours, the subject is given a meal and discharged when medically stable. After a wash-out period of 7 to 28 days, subjects return to the CRC, and the procedures are repeated with each subject crossed over to the other treatment. A follow-up visit as a safety check is conducted 2-7 days following administration of the final dose of study drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
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
- •Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24 months.
- •Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
- •Age 18 to 75 years, inclusive.
- •Random serum C-peptide concentration < 0.6 ng/mL.
- •Willingness to follow all study procedures, including attending all clinic visits.
- •Subject has provided informed consent as evidenced by a signed and dated informed consent form (ICF) completed before any trial-related activities occur.
排除标准
- •Glycated hemoglobin (HbA1c) > 10% at Screening.
- •Body mass index (BMI) > 40 kg/m
- •Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy.
- •Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or greater than 3 times the upper limit of normal.
- •Hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL.
- •Hematocrit < 30%.
- •Blood pressure (BP) readings at Screening where systolic blood pressure (SBP) < 90 or > 150 mm Hg, and diastolic blood pressure (DBP) < 50 or > 100 mm Hg.
- •Clinically significant electrocardiogram (ECG) abnormalities.
- •Use of total insulin dose per day > 2 U/kg.
- •Inadequate venous access.
- •Congestive heart failure, New York Heart Association (NYHA) class III or IV.
- •History of myocardial infarction, unstable angina, or revascularization within the past 6 months.
- •History of a cerebrovascular accident in the past 6 months or with major neurological deficits.
- •Active malignancy within 5 years from Screening, except basal cell or squamous cell skin cancers. Any history of breast cancer or malignant melanoma will be exclusionary.
- •Major surgical operation within 30 days prior to Screening.
- •Current seizure disorder (other than with suspect or documented hypoglycemia).
- •Current bleeding disorder, treatment with warfarin, or platelet count below 50 × 109 per liter.
- •History of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis, or Von Hippel-Lindau disease).
- •History of insulinoma.
- •History of allergies to glucagon or glucagon-like products, or any history of significant hypersensitivity to glucagon or any related products or to any of the excipients (DMSO and trehalose) in the investigational formulation.
- •History of glycogen storage disease.
- •Subject tests positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection (hepatitis B surface antigen positive [HBsAg+]) at Screening.
- •Active substance other than tetrahydrocannabinol (THC) or alcohol abuse (more than 21 drinks per week for male subjects or 14 drinks per week for female subject).
- •Administration of glucagon within 7 days of Screening.
- •Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before Screening for the current study and during participation in the current study.
- •Any other reason the Investigator deems exclusionary.
研究组 & 干预措施
G-Pen followed by Novo Glucagon
1 mg G-Pen at the first treatment visit followed by 1 mg Novo Glucagon at the second treatment visit
干预措施: G-Pen (Drug)
G-Pen followed by Novo Glucagon
1 mg G-Pen at the first treatment visit followed by 1 mg Novo Glucagon at the second treatment visit
干预措施: Novo Glucagon (Drug)
Novo Glucagon followed by G-Pen
1 mg Novo Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit
干预措施: G-Pen (Drug)
Novo Glucagon followed by G-Pen
1 mg Novo Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit
干预措施: Novo Glucagon (Drug)
结局指标
主要结局
Severe Hypoglycemia Rescue
时间窗: At 30 minutes following administration of study drug
Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) or an increase in plasma glucose concentration \> 20 mg/dL (\> 1.11 mmol/L) within 30 minutes after administration of glucagon
次要结局
- Plasma Glucose Response 1(At 30 minutes following a decision to administer study drug)
- Plasma Glucose Response 2(At 0-30 minutes following a decision to administer study drug)
- Administration Time(At 0-10 minutes from a decision to administer study drug)
- Hypoglycemia Resolution(At 0-90 minutes following administration of study drug)