A Randomized, Blinded, Placebo-controlled Study to Assess Pharmacokinetics, Safety, and Tolerability of Ascending Doses of MEDI0382 in Non-diabetic Obese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) for Cohorts 1, 2, and 3
研究概览
简要总结
This is a Phase 1, randomized, blinded, placebo-controlled study in up to approximately 51 non-diabetic obese participants with a body mass index (BMI) ≥ 35 kg/m^2. The participants will be observed among 3 separate cohorts and participate in the study for up to approximately 27 weeks, including a screening period (including a run-in), treatment period, and safety follow-up.
详细描述
This is a Phase 1, randomized, blinded, placebo-controlled study in up to approximately 51 non-diabetic obese participants with a BMI ≥ 35 kg/m2. Participants will be blinded, but investigators/site staff and sponsor will be unblinded for Cohort 1. In Cohorts 2 and 3 participants, investigators, and contract research organization personnel are blinded to investigational product and sponsor is unblinded. The participants will participate in the study for up to approximately 27 weeks, including a screening period (including a run-in), treatment period, and safety follow-up.
Participants will be randomized 4:1 to MEDI0382 (n=12) or placebo (n=3) for Cohort 1 and randomized 2:1 to MEDI0382 (n=12) or placebo (n=6) for Cohorts 2 and 3. In Cohort 1 participants randomized to MEDI0382 or placebo will be dosed daily with a weekly titration schedule until the highest clinically tolerated dose (CTD) is established. In Cohort 2 participants randomized to MEDI0382 or placebo will be dosed daily with a 2 week titration schedule up to the highest CTD is established in Cohort 1. In Cohort 3 participants randomized to MEDI0382 or placebo will be dosed daily with a 4 week participants schedule up to the highest CTD established in Cohort 1. Once the highest CTD is identified, participants will continue on the highest CTD for an additional 2 weeks of treatment for Cohort 1 and 3 and additional 4 weeks treatment for Cohort 2. All participants will return 28 days post last dose for a safety follow-up visit.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
In Cohort 1 participants are blinded however site staff, investigator, and sponsor are unblinded. In Cohorts 2 and 3 participants, investigators, site staff, and clinical research organization staff are blinded and sponsor is unblinded.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of written informed consent
- •Male and female participants age 18 through 65 years
- •BMI ≥ 35 kg/m^2
- •Hemoglobin A1c level of < 6.5%
- •Female participants must have a negative pregnancy test and must not be lactating.
- •Females of childbearing potential using appropriate birth control to avoid pregnancy during the study.
- •Stable body weight
- •Willing and able to adhere to the visit/protocol schedule, including following lifestyle advice with respect to diet and exercise for the duration of the study
- •Willing and able to self-administer daily SC injections following an initial self-injection training
排除标准
- •Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to Study Day 1 dosing.
- •Any condition that, in the opinion of the investigator, would interfere with the evaluation of the investigational product or interpretation of participants safety or study results.
- •Active participation in any other investigation clinical study.
- •Any prescription or non-prescription drugs for weight loss including herbal or other dietary supplements used within the past 3 months prior to screening.
- •Previous glucagon-like peptide-1 (GLP-1) use within 3 months prior to screening.
- •Any positive results for serum hepatitis B surface antigen, hepatitis C virus antibody and/or human immunodeficiency virus (HIV) antibody at screening.
- •Laboratory tests results as specified in the protocol (laboratory tests may be repeated once for confirmation of out of range values at screening).
- •Significant hepatic or renal impairment
- •Poorly controlled hypertension
- •Known or suspected history of drug or alcohol abuse within the past year or positive current test
- •Previous surgical procedures for weight loss
研究组 & 干预措施
Placebo Cohort 1
Participants will receive subcutaneous (SC) placebo matched to MEDI0382 Cohort 1 once daily for 9 weeks.
干预措施: Placebo (Drug)
MEDI0382 Cohort 1
Participants will receive SC MEDI0382 titrated doses of Dose 1 to 7 once daily (7-step titration/ 1 week per dose) from Weeks 1 to 7 followed by additional treatment of SC MEDI0382 Dose 7 once daily from Weeks 7 to 9.
干预措施: MEDI0382 (Drug)
Placebo Cohort 2
Participants will receive SC placebo matched to MEDI0382 Cohort 2 once daily for 14 weeks.
干预措施: Placebo (Drug)
MEDI0382 Cohort 2
Participants will receive SC MEDI0382 titrated doses of Doses 1, 2, 3, 5, and 7 once daily (5-step titration/ 2 week per dose) from Weeks 1 to 10 followed by additional treatment of SC MEDI0382 Dose 7 once daily from Weeks 11 to 14.
干预措施: MEDI0382 (Drug)
Placebo Cohort 3
Participants will receive SC placebo matched to MEDI0382 Cohort 3 once daily for 18 weeks.
干预措施: Placebo (Drug)
MEDI0382 Cohort 3
Participants will receive SC MEDI0382 titrated doses of Doses 1, 8, 4, and 7 once daily (4-step titration/ 4 week per dose) from Weeks 1 to 16 followed by additional treatment of SC MEDI0382 Dose 7 once daily from Weeks 17 to 18.
干预措施: MEDI0382 (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) for Cohorts 1, 2, and 3
时间窗: From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs for Cohorts 1, 2, and 3
时间窗: From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters were defined as any abnormal finding during analysis of hematology, clinical chemistry, and urinalysis.
Change in Blood Pressure from Baseline to End of Dosing as Measured by Telemetry for Cohort 1
时间窗: From Baseline (Day -1) through end of dosing (Day 63)
Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in blood pressure from baseline to end of dosing measured by telemetry for Cohort 1 are reported.
Change in Respiratory Rate from Baseline to End of Dosing as Measured by Telemetry for Cohort 1
时间窗: From Baseline (Day -1) through end of dosing (Day 63)
Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in respiratory rate from baseline to end of dosing measured by telemetry for Cohort 1 are reported.
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs for Cohorts 1, 2, and 3
时间窗: From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)
Number of participants with abnormal vital signs (body temperature, blood pressure, heart rate, and respiratory rate) and physical examinations reported as TEAEs are reported.
Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs for Cohorts 1, 2, and 3
时间窗: From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)
Number of participants with abnormal ECG parameters reported as TEAEs are reported.
Change in Pulse Rate from Baseline to End of Dosing as Measured by Telemetry for Cohort 1
时间窗: From Baseline (Day -1) through end of dosing (Day 63)
Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in pulse rate from baseline to end of dosing measured by telemetry for Cohort 1 are reported.
Change in Temperature from Baseline to End of Dosing as Measured by Telemetry for Cohort 1
时间窗: From Baseline (Day -1) through end of dosing ( Day 63)
Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in temperature from baseline to end of dosing measured by telemetry for Cohort 1 are reported.
次要结局
- Time to Maximum Observed Plasma Concentration (Tmax) of MEDI0382 for Cohort 1(Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Days 7, 14, 21, 28, 35, 42, and 49 for MEDI0382 Doses 1 to 7, respectively)
- Plasma Concentration of MEDI0382 Dose 7 on Day 71 for Cohort 2 and MEDI0382 Dose 7 on Day 113 for Cohort 3(Cohort 2: predose and 6 hours postdose on Day 71 for MEDI0382 Dose 7; Cohort 3: predose and 6 hours postdose on Day 113 for MEDI0382 Dose 7)
- Maximum Observed Plasma Concentration (Cmax) of MEDI0382 for Cohort 1(Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Days 7, 14, 21, 28, 35, 42, and 49 for MEDI0382 Doses 1 to 7, respectively)
- Cmax of MEDI0382 Dose 1 on Day 1 for Cohort 1(Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1)
- Area Under the Concentration-time Curve at the end of the Dosing interval (AUCτ) of MEDI0382 for Cohort 1(Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Days 7, 14, 21, 28, 35, 42, and 49 for MEDI0382 Doses 1 to 7, respectively)
- Plasma Concentration of MEDI0382 for Cohorts 2 and 3(Cohort 2: predose and 6 hours postdose on Days 1, 15, 29, 43, and 57 for MEDI0382 Doses 1, 2, 3, 5, and 7, respectively; Cohort 3: predose and 6 hours postdose on Days 1, 29, 57, and 85 for MEDI0382 Doses 1, 8, 4, and 7, respectively)
- AUCτ of MEDI0382 Dose 1 on Day 1 for Cohort 1(Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1)
- Tmax of MEDI0382 Dose 1 on Day 1 for Cohort 1(Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1)
- Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI0382 in all Cohorts(Predose on Baseline (Day -1) and follow-up visit (28 days after the last dose) for each cohort; predose on Days 28 and 50 for Cohort 1, on Days 7, 28, 71, 98 for Cohort 2, and on Days 7, 28, 71, 126 for Cohort 3)