Phase I Randomized Placebo Controlled Double Blind SAD and MAD Study of Oral AHRO-001 to Assess Safety, Tolerability &PK in Volunteers w/Mild/Moderate Hypercholesteremia
试验速览
- 阶段
- 1 期
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
Preclinical data support the hypothesis that the administration of AHRO-001 reduces LDL cholesterol levels, improves HDL function, and finally, decreases atheromatous plaque burden.
详细描述
4 sequential dosing cohorts, each cohort beginning with single dose (SDD), single day exposure, followed by one week of multiple daily dosing (MDD) with bid exposure, a 4 day drug honeymoon, then one week of MDD utilizing tid exposure. Each subsequent cohort utilizes the same SDD/MDD design, starting with SDD higher than prior SDD but a SDD significantly lower than prior tid MDD cohort just completed, the overall goal being to provide gradually increasing dose exposure contingent on satisfactory safety and tolerability of lower doses in the previous groups. Cohort 4 (MDD) utilizes best dose determined by Cohorts 1, 2 & 3 for 21 days.
Estimated Duration of Subject Participation: 8-9 weeks
Under Protocol Amendment Version 5.0, an additional cohort, Cohort 5, will concomitantly enroll 48 volunteers randomized to receive either AHRO-001 or placebo. Volunteers included in the study may be either currently receiving or not receiving a statin treatment. The 48 volunteers in Cohort 5 will thus be allocated to 3 treatment groups with 16 volunteers enrolled per group:
Group A: AHRO-001 alone Group B: Statin + AHRO-001 Group C: Placebo
SUBJECT POPULATION:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 OR infertile Females
- •18-70 years of age, inclusive
- •Asymptomatic mild to moderate hypercholesterolemia, (LDL =110-220 mg/dL)
- •Cohort 5: on no statin or on a stable statin dose not meeting LDL >110 mg%
- •Key Exclusion criteria
- •Fasting triglycerides <90 or >250 mg/dl (<0.85 mmol/l or >2.8 mmol/l)
- •Body Mass Index (BMI) <18 or >34 kg/m2
- •Diabetes mellitus (FBS > 125 mg% (>6.94 mmol/l)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >ULN
- •Serum creatinine >ULN for gender
- •Hemoglobin <11.5 g/dL
- •Female volunteers of childbearing potential
- •History of cancer in past 5 years
- •Any disease requiring medication
- •Use of investigational medication in past 3 months
- •Positive results for illegal drugs, HBsAg, HBsAb, HCV or HIV
- •Cohort 5:Prescription lipid lowering medications other than a statin in past 4 wks
- •Cohort 5: History of gastrointestinal tract surgical resection
排除标准
- 未提供
研究组 & 干预措施
Cohort 1, 500 mg
Cohort 1 receives SDD 500 mg AHRO-001; one week later receives MDD of 500 mg bid 7 days, then 500 mg tid 7 days
干预措施: AHRO-001 (Drug)
Cohort 2, 750 mg
Cohort 2 receives SD of 750 AHRO-001, then 7 days of 750 mg BID AHRO-001, then 7 days of 750 mg TID AHRO-001.
干预措施: AHRO-001 (Drug)
Cohort 3, 1000 mg
Cohort 3 identical design as Cohorts 1 and 2, but SD is 1000 mg AHRO-001.
干预措施: AHRO-001 (Drug)
Cohort 4, 21 day dosing
Cohort 4 receives 21 days tid administration of AHRO-001 using the best tolerated dose as determined by cohorts 1, 2 & 3
干预措施: AHRO-001 (Drug)
Cohort 5, 12 weeks dosing
Cohort 5 receives 12 weeks tid administration of AHRO-001 using the best tolerated dose as determined by the first 4 cohorts.
干预措施: AHRO-001 (Drug)
结局指标
主要结局
Number of participants with adverse events
时间窗: Participants will be followed through the course of their participation, approximately 8 weeks
To assess the safety, tolerability and pharmacokinetics of AHRO-001 when administered first as a single daily dose x 1 day, then by a graduated increase from daily dosing x 1day to twice daily dosing x7 days, and ultimately to thrice daily dosing x7. Next dose can be started as soon as 6 volunteers will finish 2 weeks of administration of the previous dose. All dose increases occur only after drug washout and are only undertaken after medical review of the previous dose as determined by symptoms, vital signs, clinical examination, clinical laboratory results, urinalyses, electrocardiograms and adverse event reporting declares that progression of dosing is safe and appropriate
次要结局
- Number of participants with adverse effects(Participants will be followed through the course of their participation, approximately 16 weeks)
- Number of participants with adverse events(Participants will be followed through the course of their participation, approximately 8 weeks)