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

115 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Evaluation of safety, tolerability and superiority of RK-01, a valsartan plus celecoxib dual add-on to metformin-HCL XR over metformin in newly diagnosed and obese adult type 2 diabetes patients with high blood pressure, arthritis and inadequate glycemic control with metformin monotherapy, diet and exercise over 26 weeks of treatment. Objective: To assess effect of RK-01 on HbA1c levels, beta cell function and insulin resistance with co-administration of valsartan, celecoxib and metformin-HCl XR relative to metformin monotherapy. Hypothesis: After 26 weeks of treatment with valsartan, celecoxib and metformin-HCl XR provides greater improvements in glycemic, inflammatory and atherogenic parameters compared to metformin monotherapy.

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.

What makes the drug combination of Valsartan, Celecoxib, and Metformin unique for treating Type 2 Diabetes?

This drug combination is unique because it combines Valsartan, a blood pressure medication, with Celecoxib, an anti-inflammatory drug, and Metformin, a common diabetes medication, potentially offering a multi-faceted approach to managing Type 2 Diabetes by addressing blood pressure, inflammation, and blood sugar levels simultaneously. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Valsartan + Celecoxib + Metformin for Type 2 Diabetes?

Research shows that combining metformin with other drugs like sitagliptin can improve blood sugar control in people with Type 2 diabetes. This suggests that combining metformin with other medications might also be effective. ^{6 7 8 9 10}

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.

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

I am taking the highest dose of Metformin.

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]

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]

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]

Citations

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

Janumet: a combination product suitable for use in patients with Type 2 diabetes. [2019]

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

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

3. United States 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. [2021]

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

Initial combination therapy with metformin and colesevelam for achievement of glycemic and lipid goals in early type 2 diabetes. [2022]

5. England 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. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Novel combination of celecoxib and metformin improves the antitumor effect by inhibiting the growth of Hepatocellular Carcinoma. [2020]

7. Greece pubmed.ncbi.nlm.nih.gov

Celecoxib and LLW-3-6 Reduce Survival of Human Glioma Cells Independently and Synergistically with Sulfasalazine. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Are metformin, statin and aspirin use still associated with overall mortality among colorectal cancer patients with diabetes if adjusted for one another? [2022]

9. England pubmed.ncbi.nlm.nih.gov

Low-dose aspirin does not lower the risk of colorectal cancer in patients with type 2 diabetes taking metformin. [2023]

10. China pubmed.ncbi.nlm.nih.gov

[Inhibitive effect of celecoxib combined with tegafur gimeracil oteracil potassium on the growth of xenograft tumor of gastric cancer in nude mice]. [2015]