Medical Dissolution of Cholesterol Gallstones Using Oral Aramchol - A Proof of Concept Phase IIa Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Complete dissolution of existing gallstones proven by repeated US examined gallbladder
研究概览
简要总结
This is a one center, Phase IIa, randomized, double blind, placebo controlled study designed to evaluate the efficacy and safety of two Aramchol doses in subjects 18 to 75 years of age, with newly formed cholesterol gallstones in their gallbladder following bariatric surgery confirmed by gallbladder ultrasound ..
详细描述
This is a one center, Phase IIa, randomized, double blind, placebo controlled study designed to evaluate the efficacy and safety of two Aramchol doses in subjects 18 to 75 years of age, with newly formed cholesterol gallstones in their gallbladder following bariatric surgery confirmed by gallbladder ultrasound performed in a period of 3 & 6 months following surgery before entering the study. All patients have ultrasonography evidence of clear gallbladder before the bariatric surgery.
Eligible subjects will be enrolled into three treatments arms: Aramchol 400 mg and 600 mg tablets and placebo tablets in ratio 1:1:1.
The subjects will be evaluated at study sites for 6 scheduled visits: at weeks -4 - 0 screening visit, Day 0 - baseline, weeks 2, 4, 8& 12 (Termination/early termination visit).
During the screening period the presence and number of cholesterol gallstones will be evaluated by gallbladder Ultrasound.
During the study the following assessments will be performed:
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female age 18 to 75 years.
- •Presence of newly formed gallstones (size up to 6 mm) with or without sludge diagnosed by ultrasound within 3 or 6 months after bariatric surgery following normal ultrasound.
- •Bariatric surgery conducted during the last 12 months
- •Patients with "sleeve gastrectomy" or laparoscopic banding of the upper stomach will be included.
- •Signature of the written informed consent.
- •Negative pregnancy test at study entry for females of child bearing potential.
- •Females of child bearing potential practicing reliable contraception throughout the study period (not including oral contraceptives).
- •Hypertensive patients must be well controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study).
- •Patients treated with vitamin E(>400IU/die), or Polyunsaturated fatty acid (>2g/d) or Ursodeoxycholic acid or fish oil can be included if drugs are stopped at least 3 months prior to study enrollment to the study and up to it end.
- •For patients with type 2 Diabetes, glycaemia must be controlled (Glycosylated Hemoglobin A1C ≤ 8% while any HbA1C increment should not exceed 1% during 6 month prior to enrollment). If glycaemia is controlled by medications, qualitative change is not permitted within 3 months prior to randomization and should be avoided during the study. Treatments with Metformin, Sulfamides and Insulin are authorized. Sulfamides and insulin are permitted if glycaemia is self-monitored by the patient.
排除标准
- •Patients with ultrasonography evidence of gallstones in gallbladder before having the bariatric surgery.
- •Patients with no clear ultrasonography evidence of gallstones -free gallbladder during the year prior their bariatric surgery.
- •Patients with ultrasonography evidence of gallstones more than 1 year following bariatric surgery.
- •Patients with ultrasonography evidence of gallstones in size greater than 9 mm less than 1 year following bariatric surgery.
- •Weight >140 Kg or BMI >40
- •Known alcohol and/or any other drug abuse or dependence in the last five years
- •Known history or presence of clinically significant cardiovascular, hepatic, gastrointestinal, neurologic, pulmonary, endocrine, psychiatric, neoplastic disorder or nephritic syndrome.
- •History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs including bile salt metabolism (e.g. inflammatory bowel disease (IDB); previous intestinal (ileal or colonic) operation; chronic pancreatic; celiac disease or previous vagotomy
- •Uncontrolled blood pressure
- •Patients with HIV
- •Patients with renal dysfunction eGFR<
- •Patients with pancreatitis, cholangitis or cholecystitis in the previous 4 months.
- •Women who are pregnant or breastfeeding
- •Type 1 Diabetes.
- •.Metformin, Fibrates, Statins, Insulin, Sulfonilurea not provided on a stable dose in the last 6 months.
- •Patients who are treated with Valproic acid, Tamoxifen, Methotreksate, Amiodaron.
- •Treatment with Rifaximin.
- •Homeopathic and/or Alternative treatments. Any treatment should be stopped before the screening period.
- •Serum creatine phosphokinase (CPK), ALT, AST and/or alkaline phosphatase >3X the upper limit of normal (ULN). Patients with an intermittent CPK elevation may have the repeated measurement prior to randomization; a CPK retest > 3X ULN leads to exclusion.
研究组 & 干预措施
Aramchol 400 mg
• One tablet of Aramchol 400 mg and one tablet of Placebo
干预措施: Aramchol (Drug)
Aramchol 400 mg
• One tablet of Aramchol 400 mg and one tablet of Placebo
干预措施: Placebo (Drug)
Aramchol 400 mg
• One tablet of Aramchol 400 mg and one tablet of Placebo
干预措施: Ultrasound (Device)
Aramchol 600 mg
• One tablet of Aramchol 400 mg and one tablet of Aramchol 200 mg.
干预措施: Aramchol (Drug)
Aramchol 600 mg
• One tablet of Aramchol 400 mg and one tablet of Aramchol 200 mg.
干预措施: Ultrasound (Device)
Placebo
• Two tablet of Aramchol matching placebo.
干预措施: Placebo (Drug)
Placebo
• Two tablet of Aramchol matching placebo.
干预措施: Ultrasound (Device)
结局指标
主要结局
Complete dissolution of existing gallstones proven by repeated US examined gallbladder
时间窗: At baseline and week 12
Change from baseline measured by US scan
次要结局
- Prevention of formation of new gallstones during the study period(At baseline and week 12)
- Dissolution of sludge.(At baseline and week 12)
- Decrease of more than a 50% in number of stones. (change from baseline)(At baseline and week 12)