A Phase 1 Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI7219 in Healthy Subjects, Including Assessment of the Impact of Changes to the Oral Formulation and Determination of Intravenous Pharmacokinetics
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Number of subjects with Adverse Events as a measure of safety and tolerability of MEDI7219
研究概览
简要总结
This is a 6-part study to evaluate the safety, tolerability, and PK of MEDI7219 in healthy subjects. Parts A, B, C & E are the single-dose parts of the study. Parts D & F are the multiple ascending dose (MAD) parts of the study. The starting dose and formulation for Parts D & F will be selected from data emerging from Parts A, B and E. Enrollment of approximately 198 subjects is anticipated.
详细描述
MEDI7219 is being developed for the potential treatment of type 2 diabetes. The study is a first in human, single and multiple ascending dose study that will try to identify the safety, tolerability and pharmacokinetics (how the drug moves through the body) of MEDI7219. The study will also look at the impact of changes to the formulation as well as differences related to the route of administration. The study will consist of 6 parts involving approximately 198 healthy male and female subjects (and up to 146 additional subjects). In Part A, 6 cohorts of 10 subjects each (with an optional 2 cohorts) will be randomized to receive MEDI7219 or one of two placebos. Each cohort will receive a different formulation of the study drug. In part B, a single cohort of 16 subjects (with an optional second cohort) will receive a different formulation of MEDI7219 per period in up to 5 periods. In Part C, up to 12 subjects will be dosed with MEDI7219. In Part D, one cohort of 30 subjects (with an optional second cohort) will be randomized to receive MEDI7219 or placebo. Subjects will start on a dose based on data from previous parts and will receive ascending doses for 35 days. In Part E, 2 cohorts of 6 subjects each (with an optional third & fourth cohort of 12 subjects each) will receive a different formulation of MEDI7219 per period. Part E, cohort 5 12 subjects each period (2 periods) has been added to assess 2 different formulations In Part F, two cohorts of 16 subjects each will be randomized to receive MEDI7219 or placebo. Subjects will start on a dose based on data from previous parts and will receive ascending doses for 35 days.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers age 18-55 years
- •BMI 18-32 kg/m2
- •Females not of childbearing potential
- •Able and willing to adhere to the protocol
- •Must provide written informed consent
排除标准
- •Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
- •Abnormal lab values, physical exam, vital signs
- •Positive drug or alcohol screen.
- •Current enrollment in another clinical study or enrollment within the past 3 months
- •Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing
- •Abnormal ECG
- •Positive Hepatitis B, Hepatitis C or HIV test
- •Positive Drug or Alcohol screen
- •Current smokers or those who have smoked within the last 12 months
- •Recent plasma or blood donation
- •Evidence of current SARS-CoV-2 infection (Part E Cohort 5 and Part F Cohort 2 only)
研究组 & 干预措施
MEDI7219
Experimental Drug
干预措施: MEDI7219 (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
Formulation without Active Drug
Formulation without Active Drug
干预措施: Formulation without Active Drug (Drug)
结局指标
主要结局
Number of subjects with Adverse Events as a measure of safety and tolerability of MEDI7219
时间窗: Baseline to last follow up visit (Parts A and C - Day 28) (Part D & F Day 63) and (Parts B and E 28 days post last dose)
Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)
次要结局
- Pharmacokinetics of MEDI7219: Cmax(Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit)
- Pharmacokinetics of MEDI7219: Tmax(Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit, Parts F cohort 2 ONLY: Pre-dose and 8 hours post-dose)
- Pharmacokinetics of MEDI7219: t1/2(Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit)
- Pharmacokinetics of MEDI7219: AUC (%extrap)(Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only))
- Pharmacokinetics of MEDI7219: AUC(0-last)(Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit)
- Pharmacokinetics of MEDI7219: Lambda-z(Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only))
- Pharmacokinetics of MEDI7219: Frel(Pre-dose to 144 hours post-dose (Parts B and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only))
- Pharmacokinetics of MEDI7219: Vd(Pre-dose to 144 hours (Part C))
- Pharmacokinetics of MEDI7219: AUC (0-tau)(Pre-dose to Day 63/EOS visit (Parts D & F))
- Pharmacokinetics of Formulation Component: Cmax(Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively))
- Pharmacokinetics of Formulation Component: Tmax(Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively))
- Pharmacokinetics of MEDI7219: AUC (0-inf)(Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit)
- Pharmacokinetics of MEDI7219: AUC(0-24h)(Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit)
- Pharmacokinetics of MEDI7219: CL/F(Pre-dose to 144 hours post-dose (Parts A, B and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only))
- Pharmacokinetics of MEDI7219: Vz/F(Pre-dose to 144 hours post-dose (Parts A, B and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Pre-dose to Day 63/EOS visit (Parts D & F))
- Pharmacokinetics of MEDI7219: F(Pre-dose to 144 hours (Part C ))
- Immunogenicity(Day -1 to Day 28/EOS Visit (Parts A and C); Day -1 to Day 63/EOS Visit (Parts D & F); Day -1 to 28 days post last dose of final period/EOS Visit (Parts B and E))
- Pharmacokinetics of Formulation Component: T(1/2)(Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively))
- Pharmacokinetics of MEDI7219: CL(Pre-dose to 144 hours post-dose (Part C))
- Pharmacokinetics of Formulation Component: AUC (0-inf)(Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively))
- Pharmacokinetics of Formulation Component: AUC (0-last)(Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively))
- Pharmacokinetics of Formulation Component: AUC (0-8h)(Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively))