Safety Study of Bile Acid to Treat Hypercholesteremia

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01931241
• Other study ID #: AHRO-001-12-101
• Status: Active, not recruiting
• Phase: Phase 1
• First received: July 10, 2013
• Last updated: November 18, 2014
• Start date: June 2013
• Est. completion date: June 2015

Study information

• Verified date: November 2014
• Source: AtheroNova Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Russian Federation	City Hospital #15	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
AtheroNova Inc.

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events	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	Participants will be followed through the course of their participation, approximately 8 weeks	Yes
Secondary	Number of participants with adverse events	To assess the safety, tolerability and pharmacokinetics of AHRO-001 dosed tid for 21 days at best tolerated dose as determined in Cohorts 1-3.	Participants will be followed through the course of their participation, approximately 8 weeks	Yes
Secondary	Number of participants with adverse effects	To assess the safety, tolerability and pharmacokinetics of AHRO-001 administered orally as a tid regimen for 12 weeks in the presence or absence of a statin, at a dose determined by safety in the first 4 dose cohorts.	Participants will be followed through the course of their participation, approximately 16 weeks	Yes