Clinical trial NCT01931241: Safety Study of Bile Acid to Treat Hypercholesteremia
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hypercholesterolemia
Keywords: atherosclerosis
atherosclerotic heart disease
hypercholesteremia
atherosclerotic plaque
hyperlipidemia
Lead sponsor: AtheroNova Inc.
Sponsor class: INDUSTRY
First posted: 2013-08-29
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Preclinical data support the hypothesis that the administration of AHRO-001 reduces LDL cholesterol levels, improves HDL function, and finally, decreases atheromatous plaque burden.

Detailed description: 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:

Healthy volunteers, both males \& infertile females, with asymptomatic mild to moderate hypercholesterolemia

Eligibility criteria: Key Inclusion Criteria:

* 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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Participants will be followed through the course of their participation, approximately 8 weeks
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: Participants will be followed through the course of their participation, approximately 8 weeks
measure: Number of participants with adverse effects
timeFrame: Participants will be followed through the course of their participation, approximately 16 weeks
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: City Hospital #15
Study officials:
affiliation: AtheroNova CMO
name: Mark K. Wedel, MD
role: STUDY_CHAIR
References: