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Type 2 DiabetesPhase 1/2RESILIENCENCT03686657

Evaluation of Superiority of Valsartan+Celecoxib+Metformin Over Metformin Alone in Type 2 Diabetes Patients

A Phase 1/2 study testing Metformin, Val, Cel and Met XR Low and Val, Cel and Met XR High in people with Type 2 Diabetes and High Blood Pressure, run by ARKAY Therapeutics at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Type 2 Diabetes, High Blood Pressure, Arthritis
What is being tested?
Metformin, Val, Cel and Met XR Low and Val, Cel and Met XR High
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
10 Dec 2026to 31 Jan 2031
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females, Age: >18 to 70 years at the time of screening visit.
  • Women of childbearing potential (WOCBP) must have negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent of HCG) within 24 hours prior to the start of the study.
  • Women must not be breastfeeding.
  • HbA1c≥8.0
  • Patients with inadequate blood glucose control with Metformin defined as a central laboratory glycosylated hemoglobin (HbA1c) >8.0 and <10.5 obtained at the screening visit. Metformin-HCl monotherapy was inadequate 3 months prior to the study as indicated by the lack of decrease and/or an increase in the A1c level.
  • Newly diagnosed drug naïve patients as defined by HbA1c>7.0 at the screening visit. Drug naïve subjects diagnosed with type 2 diabetes within 6 months of diagnosis will be considered and selected.
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  • About half the patients are expected to be newly diagnosed in the study.
  • Drug naive as well as osteoarthritis patients with Type 2 diabetes receiving a non-aspirin pain reliever (e.g. acetaminophen) or an NSAID (e.g. Naproxen).
  • Max/maintenance dose Metformin. Subjects should have been taking the same daily dose of metformin for at least 8 weeks prior to the enrollment visit and subjects not receive these other antihyperglycemic medications within the 12 weeks prior to screening (except for short-term use of insulin [≤7 days] during concomitant illness or other stress).
  • Patients with >25% AIRg at 2 minutes and 10 minutes.
  • RAS blocker naïve patients
  • 2-Hour OGTT ≥200 mg/dL
  • FPG ≥140 mg/dL
  • BMI ≥30
  • Impaired first phase and second phase of insulin secretion
  • BP ≥140/90 mm Hg (These patients might be on an anti-hypertensive drug)
  • Non-fasting laboratory glucose >200 mg/dL with symptoms of polydipsia, polyuria and/or Polyphagia
  • eGFR ≥ 60 ml/min/1.73m2

Who cannot join

  • Age >70
  • Patients with Type 1 diabetes, Screen for GAD (Glutamic acid decarboxylase) antibodies at the time of screening visit. To rule out latent autoimmune diabetes in adults (LADA), screening for other diabetes-related antibodies, such as insulinoma-associated protein (IA-2 and IA-2 beta), zinc transporter-8 (ZnT8), islet cell antibodies (ICA) or insulin autoantibody (IAA) will also be considered.
  • Pregnant women
  • Patients with a history of Ketoacidosis.
  • Subjects at serious risk of gastrointestinal (GI) adverse events (e.g. current or recent history of GI bleeding ulceration, or perforation).
  • Subjects with a planned radiologic study with intravenous contrast, surgery, or other planned procedures that may predispose them to metformin-associated lactic acidosis.
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  • Insulin dependent: <25% Beta-cell function: AIRg (Acute insulin response to glucose after 2 min and 10 min after glucose injection) INSULIN DEPENDENT STATE.
  • Patients with a history of uncontrolled hyperglycemia >15.0 mmol/L (280 mg/dL) after an overnight fast that required rescue therapy.
  • Patients with uncontrolled hyperglycemia >15.0 mmol/L (280 mg/dL) after an overnight fast that required rescue therapy during week 1-3 Metformin-HCl monotherapy or RK-01 therapy.
  • eGFR, impaired kidney function < 60 ml/min/1.73m2.
  • Poor metabolizers of Cyp450 2C9 to avoid very high concentration (Since Cytochrome 450 2C9 is responsible for the metabolism of both Valsartan and Celecoxib, patients who are known or suspected to be poor Cyp450 2C9 metabolizers based on previous history will be excluded from the study).
  • Any of the following cardiovascular (CV)/Vascular diseases within 3 months of the enrollment visit:
  • Myocardial infarction (MI)
  • Cardiac surgery or revascularization (coronary artery bypass surgery, Coronary Artery Bypass Graft [(CABG]/Percutaneous transluminal coronary angioplasty (PTCA)].
  • Unstable angina
  • Unstable congestive heart failure (CHF)
  • Transient ischemic attack (TIA) or significant cerebrovascular disease
  • Unstable or previously diagnosed arrhythmia
  • Congestive heart failure, defined as New York Heart Association (NYHA) Class III and IV, unstable or acute heart failure and/or known left ventricular ejection fraction of ≤40%.
  • Acute coronary syndrome, stroke or transient ischemic attack within 3 months prior to the informed consent.
  • Previous bariatric surgery
  • Treatment with anti-obesity drugs within 3 months prior to consent
  • Patients with COPD
  • Patients with liver disease
  • Patients with renal disease
  • Patients with autoimmune diseases e.g. Lupus, Psoriasis
  • Patients with HIV/AIDS
  • Patients with diabetes-related complications
  • Patients with Hematological and Oncological Diseases/Conditions
  • Hemoglobin <11.0 g/dL (110 g/L) for men; hemoglobin <10.0 g/dL (100 g/L) for women
  • Patients with chronic disease e.g. Cancer, Epilepsy, Alzheimer, Parkinson, Asthma
  • Abnormal free T4
  • Patients with serious infection

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Albany Medical College

    Albany, New York, 12206

Other trials in United States

About this study

Official title: A 26-week Single Site, Randomized, Double-blind, Active-controlled, Parallel Group, Human PoC Study to Evaluate Superiority of RK-01, Valsartan Plus Celecoxib Addon to Metformin Versus Metformin Alone in Type 2 Diabetes Patients

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.

Read the detailed description

PRIMARY:

In patients with type 2 diabetes with inadequate glycemic control with metformin monotherapy:

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. Improvements in glycemic, inflammatory and atherogenic parameters including beta cell function relative to adult healthy volunteers with normal glucose tolerance (NGT) treated with placebo for 26 weeks will also be assessed. An interim study assessment will also be performed after 12 weeks of treatment.

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.

Being tested
Metformin, Val, Cel and Met XR Low, Val, Cel and Met XR High
Keywords
Diabetes, Obesity, FPG, Beta cell function index, HbA1c, Atherogenic index
Medical subject headings
Diabetes Mellitus, Type 2, Hypertension, Arthritis, Obesity, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Also called Glucophage, Glucophage XR

    1000 mg metformin-HCL XR once-a-day or maintenance dose of metformin for 26 weeks

  • Val, Cel and Met XR LowDrug

    Also called Diovan, Celebrex, Glucophage XR, RK-01

    500 mg metformin-HCL XR plus 100 mg celecoxib once-a-day in the morning and 160 mg valsartan 6 hours later once-a-day in the afternoon for 26 weeks.

  • Val, Cel and Met XR HighDrug

    Also called Diovan, Celebrex, Glucophage XR, RK-01

    1000 mg metformin-HCL XR plus 200 mg celecoxib once-a-day in the morning and 320 mg valsartan once-a-day 6 hours later in the afternoon for 26 weeks.

Study groups in NCT03686657
Study groupRoleWhat they receive
Healthy adults with NGTNo interventionHealthy adults with normal glucose tolerance (NGT) and beta cell function will be administered placebo.
Metformin-Drug naive patients & Patients with inadequate glycemic control with MetforminActive comparatorPatients receive metformin once daily
Receives: Drug: Metformin
RK-01 LowExperimentalPatients receive valsartan, celecoxib and metformin (low dose) once daily
Receives: Drug: Val, Cel and Met XR Low
RK-01 HighExperimentalPatients receive valsartan, celecoxib and metformin (high dose) once daily
Receives: Drug: Val, Cel and Met XR High

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in glycosylated Hemoglobin (HbA1c) for metformin background patients

    Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline is calculated as the week 26 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage, the change from baseline is also a percentage.

    Measured: Baseline and 26 weeks

  2. Change in glycosylated Hemoglobin (HbA1c) for treatment naive patients

    Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline is calculated as the week 26 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage, the change from baseline is also a percentage.

    Measured: Baseline and 26 weeks

  3. Change from baseline in acute insulin response to glucose (AIRg) for metformin background patients

    Change in baseline in acute insulin response to glucose at week 26

    Measured: Baseline and 26 weeks

  4. Change from baseline in acute insulin response to glucose (AIRg) for treatment naive patients

    Change in baseline in acute insulin response to glucose at week 26

    Measured: Baseline and 26 weeks

Secondary outcomes (13)

  1. Change in glycosylated Hemoglobin (HbA1c) to <7.0%

    Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline is calculated as the week 26 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage, the change from baseline is also a percentage. Percentage of subjects achieving a therapeutic glycemic response, defined as HbA1c <7.0%.

    Measured: Baseline and 26 weeks

  2. Change from baseline in Body weight

    Change in body weight at week 26

    Measured: Baseline and 26 weeks

  3. Change from baseline in fasting plasma glucose

    Change in baseline in fasting plasma glucose at week 26

    Measured: Baseline and 26 weeks

  4. Change from baseline in Beta-cell function Index

    Change in baseline in beta cell function index at week 26. Beta-cell function Index is a measure of their capacity to respond to elevated blood glucose levels

    Measured: Baseline and 26 weeks

  5. Change from baseline in insulin sensitivity index (ISI or Si)

    Change in baseline in insulin sensitivity at week 26

    Measured: Baseline and 26 weeks

  6. Change from baseline in glycosylated albumin (GA): glycosylated Hemoglobin A1c (HbA1c) ratio

    Change in baseline in glycosylated albumin (GA): glycosylated Hemoglobin A1c (HbA1c) at week 26. GA:HbA1c ratio provides a measure of post-prandial excursion

    Measured: Baseline and 26 weeks

  7. Change from baseline in HOMA2-b%

    Change in baseline in HOMA of Beta-cell function index at week 26

    Measured: Baseline and 26 weeks

  8. Change from baseline in HOMA-IR

    Change in baseline in HOMA-IR at week 26. HOMA-IR is a measure of insulin resistance.

    Measured: Baseline and 26 weeks

  9. Leptin/Adiponectin ratio

    Change in baseline in Leptin/Adiponectin ratio. Indicator of insulin resistance

    Measured: Baseline and 26 weeks

  10. Change from baseline in Atherogenic Index (AI)

    Change in baseline in Atherogenic Index at week 26. Atherogenic Index (AI) is a predictor of cardiovascular risk

    Measured: Baseline and 26 weeks

  11. Change from baseline in glycosylated albumin (GA)

    Change in baseline in glycosylated albumin (GA) at week 26

    Measured: Baseline and 26 weeks

  12. Change from baseline in Leptin

    Change in baseline in Leptin at week 26

    Measured: Baseline and 26 weeks

  13. Change from baseline in Adiponectin

    Change in baseline in Adiponectin at week 26

    Measured: Baseline and 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2018
  2. Study start10 Dec 2026 (estimated)
  3. Primary completion26 Dec 2030 (estimated)
  4. Study completion31 Jan 2031 (estimated)

Why it stopped: Clinical stage asset and the sponsorship have been acquired by Myopharm Limited.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03686657
Sponsor's protocol ID
TriGlytza (RK-01) Prototype
Acronym
RESILIENCE
Status last verified
Jul 2026
First submitted
23 Sep 2018
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: Study results will be published on clinicaltrials.gov as well as a medical journal. We also plan to present the results at a conference such as American Diabetes Association's Scientific Sessions.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Metformin, Val, Cel and Met XR Low and Val, Cel and Met XR High in people with Type 2 Diabetes and High Blood Pressure, run by ARKAY Therapeutics at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in glycosylated Hemoglobin (HbA1c) for metformin background patients (time frame: Baseline and 26 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03686657.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026.

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