D-0120 + Allopurinol for Gout

Recruiting at 23 trial locations

Overseen By Kathryn Stazzone

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: InventisBio Co., Ltd

Must be taking: Allopurinol

Disqualifiers: Cancer, Pregnancy, Breastfeeding, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

D-0120 is being tested in combination with Allopurinol in adult subjects with Gout.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since the trial involves testing a new drug with Allopurinol, it's best to discuss your current medications with the study team.

Is the combination of D-0120 and Allopurinol safe for humans?

Allopurinol is generally safe for most people, but some may experience serious allergic reactions, which are rare but can be severe. These reactions can include skin rashes, fever, and kidney problems, and certain genetic factors may increase the risk. ^{1 2 3 4 5}

What makes the drug D-0120 + Allopurinol unique for treating gout?

The combination of D-0120 and Allopurinol for treating gout is unique because it potentially offers a novel approach by combining two agents, which may enhance the uric acid-lowering effects compared to Allopurinol alone. This could be particularly beneficial for patients who do not respond adequately to standard Allopurinol treatment. ^{2 6 7 8 9}

What data supports the effectiveness of the drug Allopurinol for treating gout?

Allopurinol is considered one of the most effective drugs for lowering uric acid levels in chronic gout, and it is frequently used for this purpose. It is a xanthine oxidase inhibitor, which helps prevent gout attacks by reducing uric acid production. ^{2 6 8 10 11}

Who Is on the Research Team?

Kathryn Stazzone

Principal Investigator

InventisBio Co., Ltd

Are You a Good Fit for This Trial?

Adults with gout who've had at least 2 flares in the past year can join this trial. They need to have a BMI between 18 and 40, respond poorly to urate-lowering treatments, and pass certain lab tests. Participants must not be pregnant or breastfeeding, have serious other illnesses, recent cancer history, or any condition that could risk their safety or affect study results.

Inclusion Criteria

I agree to use effective birth control during and for 30 days after the study.

I have gout and my current treatment isn't lowering my uric acid levels enough.

Body Mass Index (BMI) between 18.0 and 45.0 kg/m2 (inclusive)

Exclusion Criteria

I am not pregnant or breastfeeding.

Subjects with significant comorbidities, inadequate lab function, current (and within the past 5 years) diagnosis of cancer or any condition that, in the judgment of the investigator, would place him/her at undue risk, or potentially compromise the results or interpretation of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive D-0120 in combination with Allopurinol. Cohort A: week 1 low dose, weeks 2-12 increased dose. Cohort B: week 1 low dose, week 2 increased dose, weeks 3-12 high dose.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Allopurinol
• D-0120

Trial Overview The trial is testing D-0120 combined with Allopurinol for gout treatment. It's a Phase II study which means they're looking at how well it works and checking its safety in people who meet specific health criteria.

How Is the Trial Designed?

Group I: Cohort B Experimental Treatment 2 Interventions

week 1: D-0120 low dose in combination with Allopurinol week 2: D-0120 increased dose in combination with Allopurinol week 3-12: D-0120 high dose in combination with Allopurinol

Group II: Cohort A Experimental Treatment 2 Interventions

week 1: D-0120 low dose in combination with Allopurinol week 2-12: D-0120 increased dose in combination with Allopurinol

Allopurinol is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zyloprim for:

• Gout
• Kidney stones
• High uric acid levels after chemotherapy

Approved in European Union as Zyloric for:

• Gout
• Kidney stones
• High uric acid levels after chemotherapy

Approved in Canada as Allopurinol for:

• Gout
• Kidney stones
• High uric acid levels after chemotherapy

Approved in Japan as Allopurinol for:

• Gout
• Kidney stones
• High uric acid levels after chemotherapy

Who Is Running the Clinical Trial?

InventisBio Co., Ltd

Lead Sponsor

Trials

20

Recruited

1,800+

Published Research Related to This Trial

For patients allergic to allopurinol, alternative treatments for hyperuricemia include uricosuric drugs like probenecid and sulfinpyrazone, but these are only suitable for those with normal kidney function and no history of kidney stones.

In cases where traditional treatments are ineffective or not tolerated, options like slow oral desensitization to allopurinol or the use of oxipurinol can be beneficial, especially for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient. Fam, AG.[2022]

The management of gout involves three key stages: treating acute attacks, lowering uric acid levels to prevent future flares, and providing prophylaxis against acute attacks, with NSAIDs being the preferred treatment for acute inflammation if started early.

For chronic gout management, xanthine oxidase inhibitors like allopurinol are recommended as first-line treatments, especially for patients with renal issues or those on diuretics, while uricosuric drugs are suitable for patients allergic to allopurinol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of acute and chronic gouty arthritis: present state-of-the-art. Schlesinger, N.[2018]

A systematic review and meta-analysis of four studies found no significant association between allopurinol use and all-cause mortality in patients with gout, suggesting it is safe in this regard (adjusted HR 0.80).

While two studies indicated that allopurinol may have a protective effect against mortality, the overall evidence is limited, highlighting the need for further research to clarify its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mortality in Patients With Gout Treated With Allopurinol: A Systematic Review and Meta-Analysis. Hay, CA., Prior, JA., Belcher, J., et al.[2022]

A 56-year-old man experienced a return of acute gout symptoms after switching from the brand formulation of allopurinol (Zyloric®) to a generic version, indicating a lack of therapeutic effect from the generic.

Upon reverting to the brand formulation, the patient's symptoms improved, suggesting that not all generic medications may provide the same efficacy as their brand-name counterparts, highlighting the need for more data on the effectiveness of generic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of efficacy during the switch from brand to generic allopurinol. De Vuono, A., Scicchitano, F., Palleria, C., et al.[2013]

Allopurinol is effective in lowering serum urate levels in patients with chronic gout, showing significant improvement compared to placebo, with a number needed to treat of 1 for achieving target serum urate levels.

When compared to other urate-lowering therapies like febuxostat and benzbromarone, allopurinol demonstrated similar safety profiles and effectiveness, although febuxostat may be more effective in achieving target serum urate levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allopurinol for chronic gout. Seth, R., Kydd, AS., Buchbinder, R., et al.[2023]

In a study of 13 gout patients with severe allopurinol intolerance, febuxostat (FEB) was well tolerated in 12 patients, indicating it may be a safe alternative for those who cannot take allopurinol.

However, one patient developed a serious skin reaction (cutaneous leukocytoclastic vasculitis) during FEB treatment, highlighting the need for careful monitoring and dose escalation when prescribing FEB to patients with a history of severe allopurinol adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions. Chohan, S.[2015]

A review of 901 cases of allopurinol hypersensitivity (AH) revealed that risk factors such as renal impairment, hypertension, and the presence of the HLA-B*5801 allele are commonly associated with this serious adverse reaction, particularly in Asian populations.

The study found no significant link between higher doses of allopurinol and an increased risk of severe cutaneous reactions, challenging previous assumptions about dosage as a risk factor for AH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allopurinol hypersensitivity: a systematic review of all published cases, 1950-2012. Ramasamy, SN., Korb-Wells, CS., Kannangara, DR., et al.[2022]

Allopurinol is the most commonly prescribed medication for lowering uric acid levels in gout, but it can cause serious adverse reactions, including severe skin rashes and kidney failure, particularly in patients with certain risk factors.

The presence of the HLA-B(*)58:01 allele and high levels of its metabolite, oxypurinol, can increase the risk of these adverse reactions by enhancing T-cell sensitization, highlighting the importance of genetic testing and monitoring drug levels in patients starting allopurinol therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allopurinol hypersensitivity: investigating the cause and minimizing the risk. Stamp, LK., Day, RO., Yun, J.[2022]

In a study of over 1.6 million new allopurinol users, the incidence of hypersensitivity reactions was found to be 4.68 per 1000 new users, with significant risk factors including older age, female sex, and higher initial dosages.

Patients with asymptomatic hyperuricemia and existing renal or cardiovascular diseases faced a significantly increased risk of hypersensitivity reactions and related mortality, highlighting the need for careful prescribing in these high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allopurinol Use and Risk of Fatal Hypersensitivity Reactions: A Nationwide Population-Based Study in Taiwan. Yang, CY., Chen, CH., Deng, ST., et al.[2016]

A study involving 24 healthy male volunteers found that two brands of allopurinol tablets (200 mg) are bioequivalent, meaning they are absorbed into the body at similar rates and extents, which is important for consistent treatment of gout.

Both formulations of allopurinol were well tolerated with no reported adverse events, indicating that they are safe for use in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and comparative bioavailability of allopurinol formulations in healthy subjects. Helmy, SA., El-Bedaiwy, HM.[2018]

Benzbromarone significantly lowers plasma concentrations of oxypurinol when combined with allopurinol, but does not affect allopurinol levels, indicating a pharmacokinetic interaction.

The combination of allopurinol and benzbromarone (Allomaron) is more effective in lowering serum uric acid levels in gout patients compared to allopurinol alone, likely due to benzbromarone's uricosuric effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout. Müller, FO., Schall, R., Groenewoud, G., et al.[2022]

Citations

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

Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Management of acute and chronic gouty arthritis: present state-of-the-art. [2018]

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

Mortality in Patients With Gout Treated With Allopurinol: A Systematic Review and Meta-Analysis. [2022]

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

Lack of efficacy during the switch from brand to generic allopurinol. [2013]

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

Allopurinol for chronic gout. [2023]

6. Canada pubmed.ncbi.nlm.nih.gov

Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions. [2015]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Allopurinol hypersensitivity: a systematic review of all published cases, 1950-2012. [2022]

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

Allopurinol hypersensitivity: investigating the cause and minimizing the risk. [2022]

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

Allopurinol Use and Risk of Fatal Hypersensitivity Reactions: A Nationwide Population-Based Study in Taiwan. [2016]

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

Pharmacokinetics and comparative bioavailability of allopurinol formulations in healthy subjects. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout. [2022]