A Phase II, Fixed-sequenced, Open- Label, Research Study to Assess Pharmacokinetic Drug Interactions of AEGR-733 on Lipid-lowering Therapies in Healthy Volunteers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 125
- 试验地点
- 2
- 主要终点
- AUC0-t Atorvastatin Acid (Lomitapide 60 mg)
研究概览
简要总结
This phase II, open-label research study was conducted in 129 healthy volunteers. Each subject will be given one initial oral dose of one of 7 FDA-approved medications (probe drugs), followed by a 7 day period where subjects receive the study medication AEGR-733 at 10 or 60 mg. On study day 8 subjects will receive the second oral dose of the same probe drug that was given on day 1 and a last dose of AEGR-733 (total of 7 doses).Subjects will return in 1 week for a final safety visit. Each FDA- approved probe drug will be given to ten (10) or fifteen (15) subjects.
Safety, pharmacokinetic and pharmacodynamic assessments will be performed.
详细描述
Objectives:
Primary: To evaluate the effects of low and high doses of AEGR-733 on the pharmacokinetics of 6 FDA-approved medications that are likely to be used in combination with AEGR-733 as assessed by:
• Pharmacokinetic parameters: Cmax, Tmax, T1/2, and AUC (area under the curve).
Secondary: To evaluate the safety of AEGR-733 in combination with other lipid lowering agents in healthy subject as assessed by:
- Changes in associated liver enzymes AST, ALT and, Alkaline Phosphatase, & Total Bilirubin.
- Changes in all reported adverse events.
- To evaluate the effects of AEGR-733 in combination with other lipid lowering agents on the following lipids and lipoproteins: TC, LDL-C, VLDL, TG, HDL-C, ApoB and ApoAI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and non-pregnant/non-lactating female subjects between the ages of 18 and 70 who are in good overall health.
- •To be eligible for enrollment in this study, patients must meet all of the following criteria:
- •Men and women between the ages of 18 and 70
- •Women of child-bearing potential, that is, women not surgically sterilized and between menarche and 1 year post menopause, must test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of non-medication birth control (for example, a reliable barrier method of birth control [diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices]; partner with vasectomy; or abstinence) during the study and for one month following the last dose of study drug.
- •Subjects must be in good overall health
- •Subjects must be able to comprehend and willing to provide a signed IRB approved Informed Consent Form.
- •Subjects must be willing to comply with all study-related procedures.
排除标准
- •Known atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease
- •History of diabetes mellitus or fasting glucose > 126 mg/dL at the screening visit.
- •History of a non-skin malignancy within the previous 5 years
- •Renal insufficiency as defined by creatinine > 1.3 mg/dl
- •Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition
- •History of hypertension
- •Known coagulopathy and /or elevated PT/PTT >1.5 x ULN
- •Oral history of HIV positive
- •Patients who have undergone any organ transplant
- •Known active fibrotic or cirrhotic disease; ALT or AST > 1.5x ULN
- •Any major surgery within the previous 3 months
- •Individuals who currently use tobacco products or have done so in the previous 30 days
- •History of drug abuse (< 3 years)
- •Regular use of alcoholic beverages (> 7 drinks/day)
- •Subjects who do not agree to abstain from consuming alcoholic beverages during the entire study duration.
- •Body mass index (BMI) > 30 kg/m2 or < 18.5 kg/m2
- •Participation in an investigational drug study within 6 weeks prior to the screening visit
- •Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study will be excluded.
- •Currently taking any prescription, including oral contraceptives, or OTC medication regularly that cannot be stopped for at least 30 days prior to enrollment until completion of the study
- •Regular consumers of grapefruit juice, or have taken any medications known to be metabolized by CYP 3A4 within 4 weeks prior to the screening visit (ie. SSRIs, anti-fungals, anti-biotics, etc)
- •History of myalgia with a statin or unknown hypersensitivity to any statin, zetia, AEGR-733, or fenofibrate.
结局指标
主要结局
AUC0-t Atorvastatin Acid (Lomitapide 60 mg)
时间窗: 0 to 24 hours
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for atorvastatin acid (Lomitapide 60 mg)
AUC0-t Nicotinic Acid
时间窗: 0 to 24 hours
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for nicotinic acid
AUC0-t Simvastatin
时间窗: 0 to 24 hours
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for simvastatin
AUC0-t Simvastatin Acid
时间窗: 0 to 24 hours
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for simvastatin acid
AUC0-t Total Ezetimibe
时间窗: 0 to 24 hours
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for total ezetimibe
AUC0-t Rosuvastatin (Lomitapide 10 mg)
时间窗: 0 to 24 hours
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for rosuvastatin (Lomitapide 10 mg)
AUC0-t Fenofibric Acid
时间窗: 0 to 24 hours
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for fenofibric acid
Area Under Concentration-time Curve From 0 to Last Measureable Concentration (AUC0-t) Atorvastatin Acid (Lomitapide 10 mg)
时间窗: 0 to 24 hour
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for atorvastatin acid (Lomitapide 10 mg)
AUC0-t Rosuvastatin (Lomitapide 60 mg)
时间窗: 0 to 24 hours
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for rosuvastatin (Lomitapide 60 mg)
AUC0-t Nicotinuric Acid
时间窗: 0 to 24 hours
Geometric Mean Ratio ln(AUC0-t) Day 8/Day 1 for nicotinuric acid
次要结局
- Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)(Baseline to Day 8)