Safety Study of Bile Acid to Treat Hypercholesteremia

November 18, 2014 updated by: AtheroNova Inc.

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Anticipated)

110

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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
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
Other Names:
  • HDCA
  • Hyodeoxycholic acid
EXPERIMENTAL: 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.
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
Other Names:
  • HDCA
  • Hyodeoxycholic acid
EXPERIMENTAL: Cohort 3, 1000 mg
Cohort 3 identical design as Cohorts 1 and 2, but SD is 1000 mg AHRO-001.
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
Other Names:
  • HDCA
  • Hyodeoxycholic acid
EXPERIMENTAL: 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
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
Other Names:
  • HDCA
  • Hyodeoxycholic acid
EXPERIMENTAL: 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.
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
Other Names:
  • HDCA
  • Hyodeoxycholic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: 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
Participants will be followed through the course of their participation, approximately 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: Participants will be followed through the course of their participation, approximately 8 weeks
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
Number of participants with adverse effects
Time Frame: Participants will be followed through the course of their participation, approximately 16 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AtheroNova Inc.

Investigators

  • Study Chair: Mark K. Wedel, MD, AtheroNova CMO

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (ANTICIPATED)

June 1, 2015

Study Completion (ANTICIPATED)

June 1, 2015

Study Registration Dates

First Submitted

July 10, 2013

First Submitted That Met QC Criteria

August 26, 2013

First Posted (ESTIMATE)

August 29, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

November 20, 2014

Last Update Submitted That Met QC Criteria

November 18, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AHRO-001-12-101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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