Safety Study of Bile Acid to Treat Hypercholesteremia

NCT ID: NCT01931241

Last Updated: 2014-11-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2015-06-30

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

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

AHRO-001

Intervention Type: DRUG

Cohort 1: 500 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 2: 750 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 3: 1000 mg/dose, given as a single dose then as bid x7days and tid x7days Cohort 4: 21 days dosing given at best tolerated dose determined by cohorts 1-3 Cohort 5: 12 wks dosing given at best tolerated dose determined by cohorts 1-4

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.

Group Type: EXPERIMENTAL

AHRO-001

Intervention Type: DRUG

Cohort 1: 500 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 2: 750 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 3: 1000 mg/dose, given as a single dose then as bid x7days and tid x7days Cohort 4: 21 days dosing given at best tolerated dose determined by cohorts 1-3 Cohort 5: 12 wks dosing given at best tolerated dose determined by cohorts 1-4

Cohort 3, 1000 mg

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

Group Type: EXPERIMENTAL

AHRO-001

Intervention Type: DRUG

Cohort 1: 500 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 2: 750 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 3: 1000 mg/dose, given as a single dose then as bid x7days and tid x7days Cohort 4: 21 days dosing given at best tolerated dose determined by cohorts 1-3 Cohort 5: 12 wks dosing given at best tolerated dose determined by cohorts 1-4

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

Group Type: EXPERIMENTAL

AHRO-001

Intervention Type: DRUG

Cohort 1: 500 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 2: 750 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 3: 1000 mg/dose, given as a single dose then as bid x7days and tid x7days Cohort 4: 21 days dosing given at best tolerated dose determined by cohorts 1-3 Cohort 5: 12 wks dosing given at best tolerated dose determined by cohorts 1-4

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.

Group Type: EXPERIMENTAL

AHRO-001

Intervention Type: DRUG

Cohort 1: 500 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 2: 750 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 3: 1000 mg/dose, given as a single dose then as bid x7days and tid x7days Cohort 4: 21 days dosing given at best tolerated dose determined by cohorts 1-3 Cohort 5: 12 wks dosing given at best tolerated dose determined by cohorts 1-4

Interventions

AHRO-001

Cohort 1: 500 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 2: 750 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 3: 1000 mg/dose, given as a single dose then as bid x7days and tid x7days Cohort 4: 21 days dosing given at best tolerated dose determined by cohorts 1-3 Cohort 5: 12 wks dosing given at best tolerated dose determined by cohorts 1-4

Intervention Type: DRUG

Other Intervention Names

HDCA; Hyodeoxycholic acid

Eligibility Criteria

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%

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

AtheroNova Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark K. Wedel, MD

Role: STUDY_CHAIR

AtheroNova CMO

Locations

City Hospital #15

Moscow, , Russia

Countries

Russia

Other Identifiers

AHRO-001-12-101

Identifier Type: -

Identifier Source: org_study_id