FNP-59 for High Cholesterol

Recruiting in Palo Alto (17 mi)

Overseen by Ben Viglianti, M.D, Ph.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Benjamin Viglianti

Must not be taking: Steroids, OCP, Spironolactone, others

Disqualifiers: Pregnancy, Adrenal pathology, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This exploratory, first-in-man, phase 0 study will evaluate the feasibility of using a sub-therapeutic dose of a fluorine-18 analogue of NP-59 (\[18F\]FNP-59) to image the adrenal gland in healthy normal subjects. The researchers believe that \[18F\]FNP-59 would greatly improve the imaging characteristics, by providing a PET imaging cholesterol analogue with significantly improved radiation dosimetry.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications like steroids, oral contraceptives, spironolactone, estrogen, androgen, progesterone, ACE inhibitors, ARBs, or hormone analogue supplements to participate in this trial.

How does the drug FNP-59 differ from other high cholesterol treatments?

FNP-59, also known as fluvastatin, is unique because it is a wholly synthetic statin, unlike other statins derived from fungal metabolites. It has a short exposure time in the body and is specifically targeted to the liver, where it is rapidly metabolized, making it different from other cholesterol-lowering drugs. ^{1 2 3 4 5}

Research Team

Ben Viglianti, M.D, Ph.D.

Principal Investigator

University of Michigan

Eligibility Criteria

This trial is for healthy individuals without any adrenal gland issues. They must not be pregnant, imprisoned, or unable to consent. Participants should not be on steroids, certain blood pressure medications (ACE inhibitors/ARBs), hormone treatments like oral contraceptives, or weigh over 400 lbs.

Inclusion Criteria

My adrenal glands are healthy and I have no known adrenal diseases.

Exclusion Criteria

Pregnancy

I cannot undergo imaging tests.

I have a diagnosed adrenal gland condition.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Imaging

Participants receive a sub-therapeutic dose of [18F]FNP-59 for PET imaging to evaluate cholesterol trafficking in the adrenal gland

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

1-2 weeks

Treatment Details

Interventions

• [18F]FNP-59 (Radiopharmaceutical)

Trial Overview [18F]FNP-59 is being tested as a new PET imaging agent that could potentially provide clearer images of the adrenal glands with less radiation exposure compared to current methods. This phase 0 study involves a single sub-therapeutic dose in normal subjects.

Participant Groups

Group I: Group 1 Experimental Treatment 1 Intervention

These subjects, 6 planned (3 male, 3 female), will be to obtain normal tissue distribution of \[18F\]NP-59 and confirm calculated radiation dosimetry and optimal uptake time.

Who Is Running the Clinical Trial?

Benjamin Viglianti

Lead Sponsor

Trials

2

Recruited

30+

Findings from Research

Fluvastatin effectively lowers LDL cholesterol levels by 22-31% in patients with severe primary hypercholesterolemia and by 19-25% in those with familial hypercholesterolemia, demonstrating its efficacy as a cholesterol-lowering medication.

Fluvastatin is a cost-effective option for managing hypercholesterolemia, priced 40% lower than other statins, and has a favorable safety profile with manageable side effects, including reversible increases in liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of current clinical findings with fluvastatin. Garnett, WR.[2019]

In a study of 423 hypercholesterolemic patients, 6 weeks of treatment with fluvastatin significantly reduced harmful lipoprotein particles (apo B, LpE:B, and LpC-III:B) compared to placebo, indicating its efficacy in improving lipid profiles.

Fluvastatin treatment also led to increases in beneficial lipoproteins (apo A-I and LpA-I), suggesting that it not only lowers bad cholesterol but also enhances protective factors against coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluvastatin reduces levels of plasma apo B-containing particles and increases those of LpA-I. European Fluvastatin Study Group. Dallongeville, J., Fruchart, JC., Pfister, P., et al.[2019]

In a study of 24 patients with familial hypercholesterolemia over 104 weeks, fluvastatin significantly reduced total cholesterol by 26.8% and LDL cholesterol by 33.1%, demonstrating its efficacy in managing high cholesterol levels.

The treatment also led to a 35% reduction in the LDL-C: HDL-C ratio, indicating improved cholesterol balance, while increases in HDL cholesterol were observed, although they were variable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of fluvastatin in the long-term treatment of familial hypercholesterolemia. Koizumi, J., Haraki, T., Yagi, K., et al.[2019]

PCSK9 monoclonal antibodies (mAbs) significantly reduced LDL cholesterol levels by an average of 49.14% in patients with familial hypercholesterolemia, based on a meta-analysis of 7 clinical trials involving 926 patients.

The treatment was found to be safe, with no significant differences in common or serious adverse events compared to placebo, indicating good tolerability for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia. Ge, X., Zhu, T., Zeng, H., et al.[2022]

In a study of 38 patients with heterozygous familial hypercholesterolemia, the combination of fluvastatin and bezafibrate was more effective than fluvastatin and cholestyramine in reducing LDL cholesterol levels and improving the LDL-C/HDL-C ratio after 6 weeks of treatment.

Both drug combinations significantly lowered LDL cholesterol compared to fluvastatin alone, with no reported cases of myositis, indicating a favorable safety profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a combination fluvastatin-bezafibrate treatment for familial hypercholesterolemia: comparative analysis with a fluvastatin-cholestyramine combination. Leitersdorf, E., Muratti, EN., Eliav, O., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

A review of current clinical findings with fluvastatin. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Fluvastatin reduces levels of plasma apo B-containing particles and increases those of LpA-I. European Fluvastatin Study Group. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical efficacy of fluvastatin in the long-term treatment of familial hypercholesterolemia. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a combination fluvastatin-bezafibrate treatment for familial hypercholesterolemia: comparative analysis with a fluvastatin-cholestyramine combination. [2019]