BW-00112 for Dyslipidemia

Recruiting at 12 trial locations

Overseen By Ying N/A Zhang, Master

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Shanghai Argo Biopharmaceutical Co., Ltd.

Must be taking: Statins

Must not be taking: TG lowering, cholesterol lowering

Disqualifiers: Active pancreatitis, uncontrolled disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: 12 weeks

132 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are on a stable statin, you can continue taking it during the study. However, you must stop taking any triglyceride-lowering medications, non-prescription dietary supplements, or other cholesterol-lowering medications (except statins and ezetimibe) at least 30 days before the study starts.

Is BW-00112 (colesevelam) safe for humans?

Colesevelam, also known as BW-00112, has a favorable safety profile and is generally well-tolerated in humans. It is a bile acid-binding resin used to manage dyslipidemia and has been shown to have minimal side effects when used alone or with other medications. ^{1 2 3 4 5}

How does the drug BW-00112 differ from other dyslipidemia treatments?

BW-00112 may offer a novel approach to treating dyslipidemia by potentially targeting new pharmacological pathways, which could improve the effectiveness of traditional treatments. This could involve unique mechanisms of action not found in existing drugs like statins or bile acid sequestrants. ^{6 7 8 9 10}

What is the purpose of this trial?

A Phase 2 in Patients With Mixed Dyslipidemia

Research Team

Yuqiong N/A Li, Master

Principal Investigator

Shanghai Argo Biopharmaceutical Co., Ltd.

Eligibility Criteria

This trial is for men and women aged 18-75 with mixed dyslipidemia, who have been on a stable statin treatment for at least one month. Women must not be pregnant or breastfeeding and should be sterile or post-menopausal. Men must agree to use contraception.

Inclusion Criteria

I have signed the consent form and can follow the study rules.

My fasting triglycerides are between 150 and 500 mg/dL.

I have been on the same statin for at least 1 month and will not change it during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BW-00112 or placebo on Day 1 and Day 90

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Visits on Day 15, 30, 60, 90, 135, 225, and 270

Treatment Details

Interventions

• BW-00112

Trial Overview The study is testing BW-00112, a potential new treatment for mixed dyslipidemia in patients already using statins. It's in Phase 2, which means it's checking the effectiveness and safety of this drug.

Participant Groups

Group I: Cohort 3 Experimental Treatment 1 Intervention

BW-00112 600 mg or volume-matched placebo on Day 1 and Day 90

Group II: Cohort 2 Experimental Treatment 1 Intervention

BW-00112 300 mg or volume-matched placebo on Day 1 and Day 90

Group III: Cohort 1 Experimental Treatment 1 Intervention

BW-00112 150 mg or volume-matched placebo on Day 1 and Day 90

BW-00112 is already approved in China, United States for the following indications:

Approved in China as BW-00112 for:

• Mixed Dyslipidemia
• Severe Hypertriglyceridemia

Approved in United States as BW-00112 for:

• Mixed Dyslipidemia

Who Is Running the Clinical Trial?

Shanghai Argo Biopharmaceutical Co., Ltd.

Lead Sponsor

Trials

2

Recruited

160+

Findings from Research

In a 16-week study involving 153 Hispanic participants with primary hyperlipidemia and prediabetes, colesevelam significantly reduced LDL cholesterol levels by 19.4% compared to placebo, with 27% of participants achieving LDL levels below 100 mg/dL.

Colesevelam also led to significant improvements in glucose control, with reductions in glycated hemoglobin and fasting plasma glucose levels, indicating its potential as a treatment option for managing both cholesterol and glucose levels in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects of colesevelam in Hispanic subjects with primary hyperlipidemia and prediabetes. Rosenstock, J., Hernandez-Triana, E., Handelsman, Y., et al.[2022]

PCSK9 inhibitors, used for lipid-lowering therapy, have a low incidence of injection-site reactions leading to discontinuation, with 15 events per 1000 persons over 5 years, indicating they are generally safe.

These inhibitors do not increase the risk of serious side effects such as new-onset diabetes, neurocognitive issues, cataracts, or gastrointestinal bleeding, suggesting they are a safe option for patients needing lipid management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of proprotein convertase subtilisin/kexin 9 inhibitors: a systematic review and meta-analysis. Li, J., Du, H., Wang, Y., et al.[2022]

Recent discoveries in cholesterol and triglyceride metabolism have identified new therapeutic targets that could significantly improve cardiovascular outcomes, addressing the unmet need in dyslipidaemia treatment.

New drugs, including antisense RNAs, microRNAs, and human monoclonal antibodies, are being developed and show promise in early trials, making this a pivotal time for advancements in therapies aimed at reducing atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational therapies for hypercholesterolemia. Tomkin, GH., Owens, D.[2017]

Effective lipid-lowering agents must address the complex nature of atherosclerosis by either preventing the assembly of triglyceride-rich lipoproteins or enhancing the clearance of low-density lipoprotein (LDL) through liver receptors, as demonstrated in established animal models like apolipoprotein E- and LDL-receptor knockout mice.

Recent research emphasizes the importance of not just increasing high-density lipoprotein (HDL) levels, but also enhancing HDL function, which requires advanced in vitro and in vivo models for studying reverse cholesterol transport.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Animal and cellular models for hypolipidemic drugs. Cignarella, A.[2014]

Colesevelam hydrochloride is an effective treatment for dyslipidemia, significantly lowering serum levels of lipoproteins, and can be used alone or in combination with other medications like statins or ezetimibe.

This bile acid-binding resin has a favorable safety profile, making it a good option for patients who cannot tolerate statins or achieve their lipid goals with statin therapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colesevelam hydrochloride in the management of dyslipidemia. Armani, A., Toth, PP.[2015]

The review highlights various existing and new drug preparations for correcting dyslipidemias, focusing on their molecular mechanisms and potential pharmacological targets.

It suggests that activating the functionality of high-density lipoproteins (HDL) and exploring alternative treatments with novel mechanisms could enhance the effectiveness of traditional dyslipidemia therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological targets for dislipidemies correction. Opportunities and prospects of therapeutic usage]. Kudinov, VA., Zakharova, TS., Torkhovskaya, TI., et al.[2019]

Obesity leads to serious metabolic issues, particularly dyslipidemia, characterized by high triglycerides, low HDL cholesterol, and an increase in small-dense LDL particles, which heightens cardiovascular risk.

Effective treatment for obese patients with dyslipidemia should focus on managing risk factors and understanding the benefits and risks of medications, with future therapies potentially targeting specific metabolic pathways to address related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Obesity and dyslipidemias]. Troyo-Barriga, P.[2009]

There are four main classes of drugs for treating dyslipidemia: niacin, bile acid-binding resins, HMG-CoA reductase inhibitors, and fibric acid derivatives, each targeting different aspects of lipid metabolism.

Understanding the mechanisms of action and potential side effects of these drug classes is crucial for effective treatment, along with addressing compliance issues to ensure patients follow their prescribed therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology department: pharmacologic approaches to abnormal blood lipids. Gylys, KH.[2019]

Dyslipidemia, caused by genetic and metabolic factors, is linked to coronary artery disease (CAD), and managing lipid levels through diet and medication is crucial for preventing cardiovascular events.

While a low-fat diet is the first step in treatment, incorporating limited amounts of certain fats can help patients stick to dietary recommendations, and medications like statins and bile acid sequestrants provide effective options for controlling cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dyslipidemia and coronary artery disease. Kuo, PT.[2019]

In a study of high-risk patients switched from simvastatin therapy, the combination of ezetimibe/simvastatin led to significantly greater reductions in LDL cholesterol (37 mg/dL) compared to rosuvastatin (25 mg/dL) and atorvastatin (26 mg/dL).

All treatment regimens improved other lipid parameters, such as total cholesterol and triglycerides, with no significant differences in adverse events among the different therapies, indicating a similar safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of ezetimibe/simvastatin, rosuvastatin, and atorvastatin in uncontrolled hyperlipidemia patients. Furman, A., Meier, JL., Malmstrom, RA., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical effects of colesevelam in Hispanic subjects with primary hyperlipidemia and prediabetes. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Safety of proprotein convertase subtilisin/kexin 9 inhibitors: a systematic review and meta-analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Investigational therapies for hypercholesterolemia. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Animal and cellular models for hypolipidemic drugs. [2014]

5. England pubmed.ncbi.nlm.nih.gov

Colesevelam hydrochloride in the management of dyslipidemia. [2015]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Pharmacological targets for dislipidemies correction. Opportunities and prospects of therapeutic usage]. [2019]

7. Mexico pubmed.ncbi.nlm.nih.gov

[Obesity and dyslipidemias]. [2009]

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

Pharmacology department: pharmacologic approaches to abnormal blood lipids. [2019]

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

Dyslipidemia and coronary artery disease. [2019]

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

Comparative efficacy of ezetimibe/simvastatin, rosuvastatin, and atorvastatin in uncontrolled hyperlipidemia patients. [2018]