Safety Study of Bile Acid to Treat Hypercholesteremia

NCT01931241 | Unknown Phase 1

• 1 other identifier: AHRO-001-12-101
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypercholesterolemia

Keywords

atherosclerosis; atherosclerotic heart disease; hypercholesteremia; atherosclerotic plaque; hyperlipidemia

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Number of participants with adverse events

  Participants will be followed through the course of their participation, approximately 8 weeks

• Number of participants with adverse effects

  Participants will be followed through the course of their participation, approximately 16 weeks

Study Arms (5)

Cohort 1, 500 mg

EXPERIMENTAL

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 2, 750 mg

EXPERIMENTAL

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 3, 1000 mg

EXPERIMENTAL

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

Drug: AHRO-001

Cohort 4, 21 day dosing

EXPERIMENTAL

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 5, 12 weeks dosing

EXPERIMENTAL

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

Interventions

AHRO-001 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

Also known as: HDCA, Hyodeoxycholic acid

Cohort 1, 500 mg; Cohort 2, 750 mg; Cohort 3, 1000 mg; Cohort 4, 21 day dosing; Cohort 5, 12 weeks dosing

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males OR infertile Females
• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• AtheroNova Inc.: lead

Study Sites (1)

City Hospital #15

Moscow, Russia

Location

MeSH Terms

Conditions

Hypercholesterolemia; Atherosclerosis; Coronary Artery Disease; Plaque, Atherosclerotic; Hyperlipidemias

Interventions

hyodeoxycholic acid

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Mark K. Wedel, MD

  AtheroNova CMO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2013
• First Posted: August 29, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: November 20, 2014

Record last verified: 2014-11

Locations

RU (1)