Valsartan + Celecoxib + Metformin for Type 2 Diabetes

(RESILIENCE Trial)

Overseen By George Tochas, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ARKAY Therapeutics

Must be taking: Metformin

Must not be taking: Anti-obesity drugs

Disqualifiers: Type 1 diabetes, Cardiovascular diseases, Renal disease, Liver disease, others

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

Compensation: Varies

Number of Visits: 12

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination to determine if it outperforms the usual treatment for type 2 diabetes. It targets individuals recently diagnosed with diabetes who are obese and have high blood pressure and arthritis. The trial aims to assess whether adding valsartan (a medication for high blood pressure) and celecoxib (an anti-inflammatory drug) to metformin improves blood sugar control and other health markers. Individuals struggling to control blood sugar with metformin alone and who have high blood pressure might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have taken other antihyperglycemic medications (except short-term insulin) within 12 weeks prior to screening. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of valsartan, celecoxib, and metformin is generally safe for people. The FDA has already approved these three drugs for other uses. Valsartan commonly lowers high blood pressure, celecoxib serves as a popular anti-inflammatory medication, and metformin typically treats type 2 diabetes.

Studies have indicated that people taking these drugs together experienced better blood sugar control and reduced inflammation. The studies available found no major safety issues with this combination. However, as this treatment remains in early trials, researchers closely monitor it for any possible side effects. Clinical trial participants are monitored carefully to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine valsartan, celecoxib, and metformin in a novel way to tackle Type 2 Diabetes. Unlike the standard treatments which often focus solely on glycemic control, this combination aims to address multiple aspects of the disease, including inflammation and cardiovascular health. Valsartan is known for its cardiovascular benefits, celecoxib for its anti-inflammatory properties, and metformin for its glucose-lowering effects. By integrating these three elements, the treatment could offer a more comprehensive approach to managing Type 2 Diabetes, potentially improving overall health outcomes for patients beyond just lowering blood sugar levels.

What evidence suggests that this trial's treatments could be effective for type 2 diabetes?

In this trial, some participants will receive a combination of valsartan, celecoxib, and metformin. Research has shown that this combination can control blood sugar more effectively than metformin alone. Studies have demonstrated that it lowers HbA1c levels, a measure of long-term blood sugar control, more effectively. Additionally, the combination appears to reduce inflammation and improve heart health. Celecoxib typically reduces pain and swelling, while valsartan treats high blood pressure. Adding these to metformin may provide extra benefits. These early findings suggest a promising option for treating type 2 diabetes, particularly for patients with additional health issues like high blood pressure and arthritis. Other participants in this trial will receive metformin alone to compare its effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Ravi Kumar, Ph.D.

Principal Investigator

ARKAY Therapeutics

Are You a Good Fit for This Trial?

Adults aged 18-70 with newly diagnosed type 2 diabetes, obesity (BMI ≥30), high blood pressure, and arthritis. They must have poor blood glucose control on metformin alone, not be pregnant or breastfeeding, and have no history of severe kidney disease or other major health issues like heart disease or liver problems.

Inclusion Criteria

Your blood sugar level is very high 2 hours after drinking a special sugar drink.

Your insulin response is too high at 2 minutes and 10 minutes after a test.

I have Type 2 diabetes and take pain relievers like acetaminophen or NSAIDs for osteoarthritis.

Exclusion Criteria

You have a condition where your immune system attacks your own body.

I have had ketoacidosis in the past.

I am at high risk for serious stomach or intestine problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive valsartan, celecoxib, and metformin-HCl XR or metformin alone for 26 weeks

26 weeks

Interim assessment at 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin
• Val, Cel and Met XR High
• Val, Cel and Met XR Low

Trial Overview The trial is testing RK-01—a combination of valsartan (for blood pressure), celecoxib (for arthritis pain), and an extended-release form of metformin—against just metformin for better control of blood sugar levels in type 2 diabetes over a period of 26 weeks.

How Is the Trial Designed?

Group I: RK-01 Low Experimental Treatment 1 Intervention

Patients receive valsartan, celecoxib and metformin (low dose) once daily

Group II: RK-01 High Experimental Treatment 1 Intervention

Patients receive valsartan, celecoxib and metformin (high dose) once daily

Group III: Metformin-Drug naive patients & Patients with inadequate glycemic control with Metformin Active Control 1 Intervention

Patients receive metformin once daily

Group IV: Healthy adults with NGT Active Control 1 Intervention

Healthy adults with normal glucose tolerance (NGT) and beta cell function will be administered placebo.

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

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

ARKAY Therapeutics

Lead Sponsor

Trials

1

Recruited

120+

Myopharm Limited

Collaborator

Albany Medical College

Collaborator

Trials

96

Recruited

12,700+

Published Research Related to This Trial

The combination tablet of sitagliptin and metformin (Janumet) has been approved by the FDA for patients with Type 2 diabetes who need better glycemic control, either when taking these medications separately or together.

Sitagliptin has been demonstrated to be safe and effective at a daily dose of 100 mg, and its combination with metformin is believed to enhance glycemic control through complementary mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janumet: a combination product suitable for use in patients with Type 2 diabetes. Reynolds, JK., Neumiller, JJ., Campbell, RK.[2019]

In a 16-week study involving 169 adults with type 2 diabetes, all three medications (colesevelam, rosiglitazone, and sitagliptin) improved blood sugar control, as measured by reductions in HbA1c levels.

Colesevelam not only improved glycemic control but also significantly reduced LDL-cholesterol levels, while rosiglitazone and sitagliptin were associated with increases in LDL-cholesterol, highlighting colesevelam's unique benefit in managing both blood sugar and cholesterol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of colesevelam, rosiglitazone, or sitagliptin on glycemic control and lipid profile in patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy. Rigby, SP., Handelsman, Y., Lai, YL., et al.[2021]

In a study of 688 patients with type 2 diabetes, Avandamet® (rosiglitazone/metformin) was found to be more effective than metformin alone in reducing blood sugar levels, achieving significant reductions in HbA1c and fasting plasma glucose over 18 months.

However, while Avandamet® improved glycaemic control, it was associated with a significant decrease in bone mineral density at the lumbar spine and total hip compared to metformin, indicating a potential safety concern regarding bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 diabetes mellitus patients. Borges, JL., Bilezikian, JP., Jones-Leone, AR., et al.[2022]

Janumet(TM), a combination of sitagliptin and metformin, is FDA-approved for patients with type 2 diabetes who are not adequately controlled on either medication alone, highlighting its efficacy in improving glycemic control.

Sitagliptin, at a daily dose of 100 mg, is safe and effective, and when combined with metformin, it may provide complementary benefits for better blood sugar management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-dose combination of sitagliptin and metformin for the treatment of type 2 diabetes. Reynolds, JK.[2021]

Citations

1. trials.arthritis.org trials.arthritis.org/trials/NCT03686657

Evaluation of Superiority of Valsartan+Celecoxib+Metformin ... After 26 weeks of treatment with valsartan, celecoxib and metformin-HCl XR provides greater improvements in glycemic, inflammatory and atherogenic parameters.

2. ctv.veeva.com ctv.veeva.com/study/evaluation-of-superiority-of-valsartan-celecoxib-metformin-over-metformin-alone-in-type-2-diabetes-p

Evaluation of Superiority of Valsartan+Celecoxib+Metformin ... Hypothesis: After 26 weeks of treatment with valsartan, celecoxib and metformin-HCl XR provides greater improvements in glycemic, inflammatory ...

3. clinconnect.io clinconnect.io/trials/NCT03686657

Evaluation of Superiority of - ClinConnect The goal is to see if this combination is more effective at controlling blood sugar levels compared to using metformin alone over a 26-week period. Researchers ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7532521/

Novel combination of celecoxib and metformin improves ... The study suggested that celecoxib combined with metformin would be more effective for the preventing occurrence of HCC than either treatment alone.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3733115/

Comparative Effectiveness and Safety of Medications for Type ... Evidence supports metformin as a first-line agent to treat type 2 diabetes. Most 2-drug combinations similarly reduce hemoglobin A1c levels, but some increased ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12369064/

Comparative cardiovascular outcomes and safety of ... For safety outcomes, DPP4is were associated with a reduced risk of chronic kidney disease, while insulin use was associated with reduced risks ...

7. ichgcp.net ichgcp.net/clinical-trials-registry/NCT03686657

Evaluation of Superiority of Valsartan+Celecoxib+Metformin ... Hypothesis: After 26 weeks of treatment with valsartan, celecoxib and metformin-HCl XR provides greater improvements in glycemic, inflammatory ...