HypercholesterolemiaPhase 1NCT01931241
Safety Study of Bile Acid to Treat Hypercholesteremia
A Phase 1 study testing AHRO-001 in people with Hypercholesterolemia, run by AtheroNova Inc. at 1 site in Russia.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- AHRO-001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteRussia
- Study dates
- Jun 2013to Jun 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
Show all 13Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
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
Preclinical data support the hypothesis that the administration of AHRO-001 reduces LDL cholesterol levels, improves HDL function, and finally, decreases atheromatous plaque burden.
Read the 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
- Being tested
- AHRO-001
- Keywords
- atherosclerosis, atherosclerotic heart disease, hypercholesteremia, atherosclerotic plaque, hyperlipidemia
- Medical subject headings
- Hypercholesterolemia, Atherosclerosis, Coronary Artery Disease, Plaque, Atherosclerotic, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AHRO-001Drug
Also called HDCA, Hyodeoxycholic acid
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: AHRO-001 |
| Cohort 3, 1000 mg | Experimental | Cohort 3 identical design as Cohorts 1 and 2, but SD is 1000 mg AHRO-001. Receives: 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 Receives: 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. Receives: Drug: AHRO-001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Participants will be followed through the course of their participation, approximately 8 weeks
Secondary outcomes (2)
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.
Measured: Participants will be followed through the course of their participation, approximately 8 weeks
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.
Measured: Participants will be followed through the course of their participation, approximately 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2013 (estimated)
- Study startJun 2013
- Primary completionJun 2015 (estimated)
- Study completionJun 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AtheroNova Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark K. Wedel, MD, Study chair, AtheroNova CMO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01931241
- Sponsor's protocol ID
- AHRO-001-12-101
- Status last verified
- Nov 2014
- First submitted
- 10 Jul 2013
- Last updated
- 20 Nov 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01931241
- Acronym / sponsor ID
- AHRO-001-12-101
- Conditions
- Hypercholesterolemia
- Keywords
- atherosclerosis, atherosclerotic heart disease, hypercholesteremia, atherosclerotic plaque, hyperlipidemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- AtheroNova Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Jun 2015 (estimated)
- Study completion
- Jun 2015 (estimated)
- First posted
- 29 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1, 500 mg | Experimental | Drug: AHRO-001Cohort 1 receives SDD 500 mg AHRO-001; one week later receives MDD of 500 mg bid 7 days, then 500 mg tid 7 days |
| Cohort 2, 750 mg | Experimental | Drug: AHRO-001Cohort 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. |
| Cohort 3, 1000 mg | Experimental | Drug: AHRO-001Cohort 3 identical design as Cohorts 1 and 2, but SD is 1000 mg AHRO-001. |
| Cohort 4, 21 day dosing | Experimental | Drug: AHRO-001Cohort 4 receives 21 days tid administration of AHRO-001 using the best tolerated dose as determined by cohorts 1, 2 \& 3 |
| Cohort 5, 12 weeks dosing | Experimental | Drug: AHRO-001Cohort 5 receives 12 weeks tid administration of AHRO-001 using the best tolerated dose as determined by the first 4 cohorts. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AHRO-001Also: HDCA, Hyodeoxycholic acidCohort 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 | Drug | Cohort 1, 500 mg, Cohort 2, 750 mg, Cohort 3, 1000 mg, Cohort 4, 21 day dosing, Cohort 5, 12 weeks dosing |
Primary outcome
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
2 secondary outcomes
Number of participants with adverse events
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2014.
Related trials for Hypercholesterolemia
Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark K. Wedel, MD study chair
AtheroNova CMO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AHRO-001 in people with Hypercholesterolemia, run by AtheroNova Inc. at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (time frame: Participants will be followed through the course of their participation, approximately 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2014.