NCT03550378已完成2 期
A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MEDI0382 in Subjects With Type 2 Diabetes Mellitus and Renal Impairment
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4 Hrs) as Measured by Mixed-meal Tolerance Test (MMTT) to Day 32
研究概览
简要总结
A study to look at the effect MEDI0382 has on blood sugar in people with type 2 diabetes and kidney problems and also to check that MEDI0382 is well tolerated.
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 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 and < 85 years at screening.
- •Signed and dated written informed consent (with the exception of consent for genetic and nongenetic research) prior to performing any protocol-related procedures, including screening evaluations.
- •Diagnosed with type 2 diabetes mellitus (T2DM) with glucose control managed with any insulin and/or oral therapy combination where no significant dose changes of oral therapy of more than 50% have occurred in the 3 months prior to screening
- •Body mass index (BMI) between 25 and 45 kg/m^2 (inclusive) at screening
- •Haemoglobin A1c (HbA1c) range of 6.5 % to 10.5% (inclusive) at screening
- •Renal impairment with estimated glomerular filtration rate (eGFR) ≥ 30 and < 60 mL/min/1.73 m^2 at screening. Approximately 16 participants (40%) are required to have a screening eGFR ≥30 and < 45 mL/min/1.73 m^2 and at least 16 participants (40%) are required to have screening eGFR ≥45 and < 60 mL/min/1.73 m^
- •Females of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating. Women of childbearing potential who are sexually active with a non-sterilized male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose study drug.
排除标准
- •History or presence of significant medical or psychological conditions, including substance dependence/abuse, or significant abnormalities in laboratory parameters or vital signs including electrocardiogram (ECG), which in the opinion of the investigator, would compromise the participant's safety or successful participation in the study. As an example, severe anaemia (haemoglobin < 7.0 g/dL) could be exclusionary due to blood sampling required by the protocol, at the discretion of investigator.
- •Concurrent participation in another interventional study of any kind and repeat randomisation in this study is prohibited.
- •Any participant who has received another study drug as part of a clinical study or a glucagon-like peptide-1 (GLP-1) analogue-containing preparation within the last 30 days or 5 half-lives of the drug (if known; whichever is longer) at the time of Visit
- •Any participant who has received any of the following medications within the specified timeframe prior to the start of the study (Visit 2)
- •Herbal preparations within 1 week prior to the start of dosing (Visit 4) or drugs licensed for control of body weight or appetite (eg, orlistat, bupropion-naltrexone, phentermine-topiramate, phentermine, lorcaserin) within 30 days (or 5 half-lives of the drug) prior to the start of dosing (Visit 4)
- •Aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily and within the last 3 days prior to the start of the run-in period (Visit 2)
- •Paracetamol (acetaminophen) or paracetamol-containing preparations at a total daily dose of greater than 3000 mg and within the last 3 days prior to the start of the run-in period (Visit 2)
- •Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000 mg and within the last 3 days prior to the start of the run-in period (Visit 2)
- •Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying and within 2 weeks prior to the start of dosing (Visit 4)
- •Severe allergy/hypersensitivity to any of the proposed study treatments or excipients
- •Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis
- •Participants who have undergone a renal transplant
- •Participants with suspicion of acute or subacute renal function deterioration (eg, participants with large fluctuations of creatinine values documented within the 6 months prior to screening)
- •Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper gastrointestinal (GI) tract including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
- •History of acute or chronic pancreatitis
- •Significant hepatic disease (except for non-alcoholic steatohepatitis or nonalcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results:
- •Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN)
- •Alanine transaminase (ALT) ≥ 3 × ULN
- •Total bilirubin ≥ 2 × ULN
- •Poorly controlled hypertension defined as:
- •Systolic blood pressure (BP) > 180 mm Hg
- •Diastolic BP ≥ 100 mm Hg Participants who fail BP screening criteria may be considered for 24-hour ambulatory blood pressure monitoring (ABPM) at the discretion of the investigator. Participants who maintain a mean 24-hour systolic BP ≤ 180 or diastolic BP < 100 mm Hg with a preserved nocturnal dip of > 15% will be considered eligible
- •Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke within 3 months prior to screening, or participants who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening
- •Severe congestive heart failure (New York Heart Association Class III or IV)
- •Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
- •History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
- •Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody
- •Nephrotic range proteinuria defined as spot urine albumin creatinine ratio (ACR) > 250 mg/mmol at screening
- •History of substance dependence, alcohol abuse, or excessive alcohol intake (defined as an average weekly intake of > 21 alcoholic drinks for men or > 10 alcoholic drinks for women) within 3 years prior to screening, and/or a positive screen for drugs of abuse or alcohol at screening or on Day -
- •Participants who use tricyclic antidepressants or benzodiazepines for an established clinical indication may be permitted to enter the study based upon the judgement of the investigator
研究组 & 干预措施
MEDI0382
Experimental
Participants will receive subcutaneous (SC) dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
干预措施: MEDI0382 (Drug)
Placebo
Placebo Comparator
Participants will receive SC dose of placebo matched to MEDI0382 once daily for 32 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change From Baseline in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4 Hrs) as Measured by Mixed-meal Tolerance Test (MMTT) to Day 32
时间窗: Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -5 (Baseline) and Day 32
The MMTT involved the consumption of a standardised liquid meal (a nutritional supplement containing the components of fat, carbohydrate, and protein, which make up a standard MMTT) within 15 minutes, and timed serial blood samples obtained for measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardized meal (with no additional food intake during this time).
次要结局
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs(Day 1 through Day 60)
- Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESIs)(Day 1 through Day 60)
- Change From Baseline in Mean 24-hrs Pulse Rate to the End of Each Dosing Level(Day -5 (Baseline) and on Days 5, 12, 19, and 32)
- Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level(Day -5 (Baseline) and on Days 5, 12, 19, and 32)
- Change From Baseline in Haemoglobin A1c (HbA1c) to Day 32(Day 1 (Baseline) and Day 32)
- Change From Baseline in Fasting Glucose to Day 32(Day 1 (Baseline) and Day 32)
- Change From Baseline in Percentage of Time Spent Within a Target Glucose Range Over a 7-day Period to the Final Week of Treatment(Baseline (Days -8 to -2), Days 5 to 11, Days 12 to 18, Days 19 to 25, and Days 26 to 32 (final week of treatment))
- Percent Change Frome Baseline in Body Weight to Day 33(Day 1 (Baseline) and Day 33)
- Change From Baseline in Absolute Body Weight to Day 33(Day 1 (Baseline) and Day 33)
- Area Under the Plasma Concentration Time Curve Over a Dosing Duration (AUCτ) of MEDI0382 at 300 μg(Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32)
- Maximum Observed Serum Concentration (Cmax) of MEDI0382 at 300 μg(Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32)
- Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 at 300 μg(Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32)
- Number of Participants With Abnormal Vital Signs Reported as TEAEs(Day 1 through Day 60)
- Change From Baseline in Postural Blood Pressure(Baseline (Day 1) through Day 32)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(Day 1 through Day 60)
- Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs(Day 1 through Day 60)
- Trough Plasma Concentration (Ctrough) of MEDI0382(Days 1, 5, 12, and 19: Predose; and Day 32: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose (Day 33))
- Number of Participants With Positive Anti-drug Antibodies (ADA) Titre to MEDI0382(Pre-dose on Days 1, 12, and 32 and on Day 60)
研究者
研究点 (1)
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