A Phase 2, Single-Dose, Randomized, Open-Label, Active-Controlled, Crossover, Pharmacodynamic, and Pharmacokinetic Comparative Study of a Novel Pramlintide-Insulin Co-Formulation in Adults With Type 1 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL
研究概览
简要总结
This is a randomized, open-label, active-controlled, single-dose, 3-treatment, 3-period, 3-way crossover, comparative PD and PK inpatient study in adults with T1D. The study comprises 5 visits: Screening (Visit 1), Treatment Periods (Visits 2 - 4), and Follow-Up (Visit 5).
详细描述
The primary objective of this study is to evaluate the PD properties of a single dose of PRAM9 compared to single doses of regular insulin and regular insulin plus pramlintide (co-administered as separate injections) in adults with T1D. The secondary objectives of this study are to evaluate the safety and PK profiles of a single dose of PRAM9 compared to single doses of regular insulin and regular insulin plus pramlintide (co-administered as separate injections) in adults with T1D. During each treatment period subjects will receive a single SC dose of PRAM9, regular insulin, or co-administered regular insulin plus pramlintide.
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
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Understands the study procedures, alternative treatment available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent
- •Male or non-pregnant, non-lactating female diagnosed with T1D for at least 24 months prior to Screening.
- •Aged 18 to 64 years of age, inclusive
- •On a stable insulin regimen for 21 days prior to Screening (no greater than ± 20% variability in total daily dose)
- •Have a plasma C-peptide level < 0.6 ng/mL at Screening
- •Have an HbA1c < 10% at Screening
- •Body mass index (BMI) in the range of ≥ 18 to ≤ 35 kg/m2 at Screening
- •For women of childbearing potential, there is a requirement for a negative urine pregnancy test at Screening and for agreement to use contraception throughout the study and for 7 days after the last dose of study drug. Acceptable contraception includes birth control pill/patch/vaginal ring, Depo-Provera® (medroxyprogesterone acetate), Norplant® System (levonorgestrel), an intra-uterine device (IUD), the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
- •Fasting Serum triglyceride concentration < 200 mg/dL
排除标准
- •Currently being treated with pramlintide or has discontinued pramlintide within 21 days of Screening
- •Currently using an insulin pump
- •Has renal insufficiency (serum creatinine <3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy
- •Has hepatic disease, including serum ALT or AST ≥3 times the upper limit of normal (ULN)
- •Has hepatic synthetic insufficiency (serum albumin <3.0 g/dL)
- •Has a hematocrit value that is exclusionary: Female <35.5% and Male <38.3%
- •Has a hemoglobin value that is exclusionary: Female <11.5 g/dL and Male <12.5 g/dL
- •Has out-of-range systolic or diastolic BP readings at Screening (systolic BP <90 or >150 mm Hg or diastolic BP <50 or >100 mm Hg)
- •Has clinically significant ECG abnormalities at Screening
- •Has congestive heart failure, NYHA Class III or IV
- •Has history of myocardial infarction, unstable angina, or revascularization within 6 months prior to Screening
- •Has history of a cerebrovascular accident in 6 months prior to Screening with major neurological deficits
- •Has active malignancy within 5 years prior to Screening (exception: basal cell or squamous cell skin cancers)
- •Has had major surgical operation within 60 days prior to Screening or planned surgical operation during the study
- •Has a seizure disorder (other than with suspected or documented hypoglycemia)
- •Has a current bleeding disorder, treatment with anticoagulants, or platelet count <50 ×10^9/L
- •Has a history of allergies or significant hypersensitivity to pramlintide or any pramlintide-related products or to any of the excipients in the investigational formulation
- •Has a history of positive test result for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
- •Has a concurrent illness not controlled by a stable therapeutic regimen
- •Tests positive for drugs of abuse at Screening. Subjects testing positive for tetrahydrocannabinol (THC) at Screening or reporting active marijuana use will be allowed to participate in the study at the discretion of the investigator.
- •Has active substance or alcohol abuse (>21 drinks/week for males or >14 drinks/week for females)
- •Has participated in other studies involving administration of an investigational drug within 30 days or 5 half-lives prior to Screening (whichever is longer) or during participation in the current study
- •There is any reason the investigator deems exclusionary
- •Has donated blood within 8 weeks prior to Screening.
研究组 & 干预措施
PRAM9 to Regular Insulin to Regular Insulin+pramlintide
Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections
干预措施: PRAM9 (Drug)
PRAM9 to Regular Insulin to Regular Insulin+pramlintide
Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections
干预措施: Regular Insulin + Pramlintide (Drug)
PRAM9 to Regular Insulin to Regular Insulin+pramlintide
Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections
干预措施: Regular Insulin (Drug)
Regular Insulin to Regular Insulin+pramlintide to PRAM9
Regular Insulin (Humulin®) to Regular Insulin+pamlintide (Symlin® pen) as separate SC injections to PRAM9
干预措施: PRAM9 (Drug)
Regular Insulin to Regular Insulin+pramlintide to PRAM9
Regular Insulin (Humulin®) to Regular Insulin+pamlintide (Symlin® pen) as separate SC injections to PRAM9
干预措施: Regular Insulin + Pramlintide (Drug)
Regular Insulin to Regular Insulin+pramlintide to PRAM9
Regular Insulin (Humulin®) to Regular Insulin+pamlintide (Symlin® pen) as separate SC injections to PRAM9
干预措施: Regular Insulin (Drug)
Regular Insulin+pramlintide to PRAM9 to Regular Insulin
Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin
干预措施: PRAM9 (Drug)
Regular Insulin+pramlintide to PRAM9 to Regular Insulin
Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin
干预措施: Regular Insulin + Pramlintide (Drug)
Regular Insulin+pramlintide to PRAM9 to Regular Insulin
Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin
干预措施: Regular Insulin (Drug)
PRAM9 to Regular Insulin+pramlintide to Regular Insulin
Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin
干预措施: PRAM9 (Drug)
PRAM9 to Regular Insulin+pramlintide to Regular Insulin
Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin
干预措施: Regular Insulin + Pramlintide (Drug)
PRAM9 to Regular Insulin+pramlintide to Regular Insulin
Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin
干预措施: Regular Insulin (Drug)
Regular Insulin to PRAM9 to Regular Insulin+pramlintide
Regular Insulin (Humulin®) to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin
干预措施: PRAM9 (Drug)
Regular Insulin to PRAM9 to Regular Insulin+pramlintide
Regular Insulin (Humulin®) to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin
干预措施: Regular Insulin + Pramlintide (Drug)
Regular Insulin to PRAM9 to Regular Insulin+pramlintide
Regular Insulin (Humulin®) to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin
干预措施: Regular Insulin (Drug)
Regular Insulin+pramlintide to Regular Insulin to PRAM9
Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin to Xeris pramlintide + insulin co-formulation (PRAM9)
干预措施: PRAM9 (Drug)
Regular Insulin+pramlintide to Regular Insulin to PRAM9
Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin to Xeris pramlintide + insulin co-formulation (PRAM9)
干预措施: Regular Insulin + Pramlintide (Drug)
Regular Insulin+pramlintide to Regular Insulin to PRAM9
Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin to Xeris pramlintide + insulin co-formulation (PRAM9)
干预措施: Regular Insulin (Drug)
结局指标
主要结局
Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL
时间窗: 0-180 minutes following administration of study drug
The PD effects on plasma glucose levels were compared among the treatment arms as defined by AUC0-180 (mg/dL \* minutes) for plasma glucose \>180 mg/dL
次要结局
- Plasma Glucose Cmax(Up to 360 minutes following administration of study drug)
- Insulin Tmax(Up to 360 minutes following administration of study drug)
- Plasma Glucose Tmax(Up to 360 minutes following administration of study drug)
- Pramlintide Tmax(Up to 360 minutes following administration of study drug)
- Insulin Cmax(Up to 360 minutes following administration of study drug)
- Mean Proportional Time for Plasma Glucose Levels(Up to 360 minutes following administration of study drug)
- Area Under the Concentration (AUC) Curve for Plasma Glucose(Up to 360 minutes following administration of study drug)
- Pramlintide Cmax(Up to 360 minutes following administration of study drug)
- Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL(During 40 to 180 minutes post-injection of study drug)
- Area Over the Concentration (AOC) Curve for Plasma Glucose(Up to 360 minutes following administration of study drug)
- Insulin Area Under the Concentration (AUC) Curve(Up to 360 minutes following administration of study drug)
- Pramlintide Area Under the Concentration (AUC) Curve(Up to 360 minutes following administration of study drug)