Safety Study of Bile Acid to Treat Hypercholesteremia

AtheroNova

Status and phase: Unknown; Phase 1

Conditions: Hypercholesterolemia

Treatments: Drug: AHRO-001

Study type: Interventional

Funder types: Industry

Identifiers

NCT01931241

AHRO-001-12-101

Details and patient eligibility

About

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

Full 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

Enrollment: 110 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

---

110 participants in 5 patient groups

Cohort 1, 500 mg

Experimental group

Description:

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

Treatment:

Drug: AHRO-001

Cohort 2, 750 mg

Experimental group

Description:

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.

Treatment:

Drug: AHRO-001

Cohort 3, 1000 mg

Experimental group

Description:

Cohort 3 identical design as Cohorts 1 and 2, but SD is 1000 mg AHRO-001.

Treatment:

Drug: AHRO-001

Cohort 4, 21 day dosing

Experimental group

Description:

Cohort 4 receives 21 days tid administration of AHRO-001 using the best tolerated dose as determined by cohorts 1, 2 \& 3

Treatment:

Drug: AHRO-001

Cohort 5, 12 weeks dosing

Experimental group

Description:

Cohort 5 receives 12 weeks tid administration of AHRO-001 using the best tolerated dose as determined by the first 4 cohorts.

Treatment:

Drug: AHRO-001