A Phase 1, Randomized, Double-blind, Placebo- and Positive-controlled, Parallel Group Study With Nested Crossover Comparison to Assess the Effect of Maridebart Cafraglutide on QT/QTc Intervals in Participants Living With Overweight or Obesity
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Amgen
- 入组人数
- 81
- 试验地点
- 2
- 主要终点
- Change from Baseline in QTcF for Maridebart Cafraglutide
研究概览
简要总结
The main objective of this trial is to evaluate the effect of maridebart cafraglutide subcutaneously (SC) on the placebo-corrected, change from baseline in QT interval corrected for heart rate using Fridericia's formula in participants living with overweight or obesity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To take part in the trial, participants must meet all of the following:
- •Provide signed and dated informed consent before any trial procedures.
- •Be able to understand the trial requirements, sign the consent form, and follow trial restrictions.
- •Male or female, of any race, between 18 and 60 years old (inclusive).
- •Females must not be pregnant or breastfeeding.
- •Males and females who could become pregnant must agree to use effective birth control as specified in the protocol.
- •Body mass index (BMI) between 25.0 and 35.0 kg/m^2 (inclusive).
- •No major changes in diet or lifestyle in the past 3 months, based on self-report.
- •Stable body weight (less than 5 kg change) in the past 3 months, based on self-report.
- •Blood potassium, calcium, and magnesium within the normal range at screening and at check-in for the first treatment period.
- •Participants with controlled high blood pressure, cholesterol problems, or hypothyroidism on stable treatment for at least 3 months may be included (except for medicines known to affect heart rhythm or interact with moxifloxacin). Other mild, stable health conditions may be allowed with approval from the investigator and medical monitor.
排除标准
- •Participants will not be able to take part if they meet any of the following:
- •Medical Conditions
- •Any significant medical condition or abnormal test result that, in the opinion of the investigator, could pose a risk or interfere with trial participation.
- •History of diabetes (any type, except past gestational diabetes), or Haemoglobin A1c (HbA1c) ≥ 6.5% at screening.
- •History of pancreatitis within the past year, or high blood tests suggesting pancreatic problems (lipase/amylase > 2× normal, or fasting triglycerides > 500 mg/dL).
- •Liver enzymes (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) more than 2× the upper limit of normal.
- •Kidney function (estimated glomerular filtration rate [eGFR]) < 70 mL/min/1.73 m^
- •Cancer within the last 5 years (except treated nonmelanoma skin cancers or in situ cervical/breast lesions).
- •Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type
- •Uncontrolled thyroid disease (abnormal thyroid-stimulating hormone [TSH] outside 0.4-6.0 mIU/L).
- •Contraindications to moxifloxacin, including history of tendon disorders with quinolone use.
- •History of gastrointestinal surgery or disease that may affect absorption of oral drugs (other than uncomplicated appendectomy or hernia repair).
- •Inability to swallow pills.
- •History of significant esophageal, stomach, or bowel disorders (eg, ulcers, bleeding, Crohn's disease, ulcerative colitis, irritable bowel syndrome, gastroparesis).
- •Current or recent suicidal thoughts (per Columbia Suicide Severity Rating Scale [C-SSRS]).
- •Lifetime history of suicide attempt or behavior.
- •Major depressive disorder within the past 2 years.
- •History of other serious psychiatric disorders (eg, schizophrenia, bipolar disorder).
- •High depression score (patient health questionnaire-9 [PHQ-9] ≥ 15).
- •History or current signs of heart disease (eg, heart attack, congenital defects, valve disease, angina, bypass or stent).
- •History of ischemic optic neuropathy (eye damage from poor blood flow).
- •Diagnosis of sleep apnea. Diagnostic Tests
- •Positive test for human immunodeficiency virus (HIV).
- •Positive test for hepatitis B or C (exceptions apply for prior vaccination or resolved infection).
- •Abnormal vital signs: average blood pressure > 140/90 mmHg or < 90/50 mmHg, or heart rate > 110 or < 40 bpm.
- •Abnormal ECG findings at screening or check-in, including:
- •QTcF > 450 ms (males) or > 470 ms (females).
- •QRS > 120 ms, PR > 220 ms, AV block (2nd or 3rd degree).
- •Findings that make QTc measurement unreliable.
- •Risk factors for dangerous arrhythmias (eg, heart failure, low potassium, long QT syndrome).
- •Clinically significant arrhythmias. Medications
- •Use of drugs that affect absorption, metabolism, or elimination within 30 days of dosing.
- •Use of drugs known to prolong QT/QTc within 30 days of dosing.
- •Use of prescription drugs (other than hormone replacement or contraception) within 14 days of dosing.
- •Use of long-acting/slow-release medicines still active within 14 days of dosing.
- •Use of non-prescription products (vitamins, supplements, herbal products) within 7 days of dosing.
- •Use of glucagon-like peptide-1 (GLP-1) or glucose-dependent insulinotropic polypeptide (GIP) receptor agonists/antagonists within 3 months of check-in.
- •Other Clinical Trial Experience
- •Participation in another investigational drug trial within 30 days or 5 drug half-lives (whichever is longer).
- •Previous exposure to maridebart cafraglutide in this or another trial. Lifestyle
- •Alcohol use > 21 units/week (men) or > 14 units/week (women).
- •Alcohol use within 48 hours before check-in.
- •Positive drug screen or alcohol test at screening or check-in.
- •History of alcohol or drug abuse within 1 year.
- •Use of tobacco/nicotine products within 3 months, or positive cotinine test.
- •Use of caffeine within 48 hours of screening or check-in.
- •Consumption of grapefruit, Seville orange, or related products within 7 days of check-in.
- •Consumption of poppy seed-containing foods within 7 days of check-in. Other
- •Receipt of blood products within 2 months before check-in.
- •Blood donation within 3 months; plasma donation within 2 weeks; platelet donation within 6 weeks.
- 另有 2 项未显示
研究组 & 干预措施
Group 2A
In treatment period 1, participants will receive moxifloxacin.
In treatment period 2, participants will receive placebo for maridebart cafraglutide.
In treatment period 3, participants will receive placebo for moxifloxacin.
干预措施: Placebo for Maridebart Cafraglutide (Drug)
Group 2A
In treatment period 1, participants will receive moxifloxacin.
In treatment period 2, participants will receive placebo for maridebart cafraglutide.
In treatment period 3, participants will receive placebo for moxifloxacin.
干预措施: Placebo for Moxifloxacin (Drug)
Group 2B
In treatment period 1, participants will receive placebo for moxifloxacin.
In treatment period 2, participants will receive placebo for maridebart cafraglutide.
In treatment period 3, participants will receive moxifloxacin.
干预措施: Moxifloxacin (Drug)
Group 1
In treatment period 1, participants will receive placebo for moxifloxacin.
In treatment period 2, participants will receive maridebart cafraglutide.
In treatment period 3, participants will receive placebo for moxifloxacin.
干预措施: Maridebart Cafraglutide (Drug)
Group 1
In treatment period 1, participants will receive placebo for moxifloxacin.
In treatment period 2, participants will receive maridebart cafraglutide.
In treatment period 3, participants will receive placebo for moxifloxacin.
干预措施: Placebo for Moxifloxacin (Drug)
Group 2A
In treatment period 1, participants will receive moxifloxacin.
In treatment period 2, participants will receive placebo for maridebart cafraglutide.
In treatment period 3, participants will receive placebo for moxifloxacin.
干预措施: Moxifloxacin (Drug)
Group 2B
In treatment period 1, participants will receive placebo for moxifloxacin.
In treatment period 2, participants will receive placebo for maridebart cafraglutide.
In treatment period 3, participants will receive moxifloxacin.
干预措施: Placebo for Maridebart Cafraglutide (Drug)
Group 2B
In treatment period 1, participants will receive placebo for moxifloxacin.
In treatment period 2, participants will receive placebo for maridebart cafraglutide.
In treatment period 3, participants will receive moxifloxacin.
干预措施: Placebo for Moxifloxacin (Drug)
结局指标
主要结局
Change from Baseline in QTcF for Maridebart Cafraglutide
时间窗: Up to Day 171
Change from baseline in QTcF for maridebart cafraglutide will be the dependent variable for calculation of model-derived placebo-corrected, change from baseline in QTcF after maridebart cafraglutide dosing.
次要结局
- Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) of Maridebart Cafraglutide(Up to Day 171)
- Maximum Observed Concentration (Cmax) of Maridebart Cafraglutide(Up to Day 171)
- Change from Baseline in Heart Rate(Up to Day 171)
- Change from Baseline in PR Interval(Up to Day 171)
- Change from Baseline in QRS Duration(Up to Day 171)
- Categorical Outliers for QTcF(Up to Day 171)
- Categorical Outliers for HR(Up to Day 171)
- Categorical Outliers for PR(Up to Day 171)
- Categorical Outliers for QRS(Up to Day 171)
- Number of Participants with Treatment-emergent Changes in Electrocardiogram (ECG) Morphology(Up to Day 171)
- Change from Baseline in QTcF for Moxifloxacin(Up to Day 171)
- Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events(Up to Day 232)
- Number of Participants with Anti-maridebart Cafraglutide Antibody Formation(Up to Day 232)