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NCT03686657 | NOT YET RECRUITING | Type 2 Diabetes

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

ARKAY Therapeutics

Brief 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 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.

Condition or disease

Type 2 Diabetes

High Blood Pressure

Arthritis

Obesity

Intervention/treatment

Metformin

Val, Cel and Met XR Low

Val, Cel and Met XR High

Phase

PHASE1

PHASE2

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.

Study Type : INTERVENTIONAL
Estimated Enrollment : 115 participants
Masking : TRIPLE
Primary Purpose : TREATMENT
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
Actual Study Start Date : 2025-10-10
Estimated Primary Completion Date : 2028-11-26
Estimated Study Completion Date : 2029-01-31

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years to 70 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Inclusion Criteria
  • 1. Males and females, Age: \>18 to 70 years at the time of screening visit.
  • 2. 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.
  • 3. Women must not be breastfeeding.
  • 4. HbA1c≥8.0
  • 5. 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.
  • About half the patients are expected to be newly diagnosed in the study.
  • 6. 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).
  • 7. 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).
  • 8. Patients with \>25% AIRg at 2 minutes and 10 minutes.
  • 9. RAS blocker naïve patients
  • 10. 2-Hour OGTT ≥200 mg/dL
  • 11. FPG ≥140 mg/dL
  • 12. BMI ≥30
  • 13. Impaired first phase and second phase of insulin secretion
  • 14. BP ≥140/90 mm Hg (These patients might be on an anti-hypertensive drug)
  • 15. Non-fasting laboratory glucose \>200 mg/dL with symptoms of polydipsia, polyuria and/or Polyphagia
  • 16. eGFR ≥ 60 ml/min/1.73m2
Exclusion Criteria
  • 1. Age \>70
  • 2. 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.
  • 3. Pregnant women
  • 4. Patients with a history of Ketoacidosis.
  • 5. Subjects at serious risk of gastrointestinal (GI) adverse events (e.g. current or recent history of GI bleeding ulceration, or perforation).
  • 6. Subjects with a planned radiologic study with intravenous contrast, surgery, or other planned procedures that may predispose them to metformin-associated lactic acidosis.
  • 7. Insulin dependent: \<25% Beta-cell function: AIRg (Acute insulin response to glucose after 2 min and 10 min after glucose injection) INSULIN DEPENDENT STATE.
  • 8. Patients with a history of uncontrolled hyperglycemia \>15.0 mmol/L (280 mg/dL) after an overnight fast that required rescue therapy.
  • 9. 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.
  • 10. eGFR, impaired kidney function \< 60 ml/min/1.73m2.
  • 11. 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).
  • 12. Any of the following cardiovascular (CV)/Vascular diseases within 3 months of the enrollment visit
    • 1. Myocardial infarction (MI)
    • 2. Cardiac surgery or revascularization (coronary artery bypass surgery, Coronary Artery Bypass Graft \[(CABG\]/Percutaneous transluminal coronary angioplasty (PTCA)\].
    • 3. Unstable angina
    • 4. Unstable congestive heart failure (CHF)
    • 5. Transient ischemic attack (TIA) or significant cerebrovascular disease
    • 6. Unstable or previously diagnosed arrhythmia
    • 7. 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%.
    • 8. Acute coronary syndrome, stroke or transient ischemic attack within 3 months prior to the informed consent.
    • 13. Previous bariatric surgery
    • 14. Treatment with anti-obesity drugs within 3 months prior to consent
    • 15. Patients with COPD
    • 16. Patients with liver disease
    • 17. Patients with renal disease
    • 18. Patients with autoimmune diseases e.g. Lupus, Psoriasis
    • 19. Patients with HIV/AIDS
    • 20. Patients with diabetes-related complications
    • 21. Patients with Hematological and Oncological Diseases/Conditions
    • 22. Hemoglobin \<11.0 g/dL (110 g/L) for men; hemoglobin \<10.0 g/dL (100 g/L) for women
    • 23. Patients with chronic disease e.g. Cancer, Epilepsy, Alzheimer, Parkinson, Asthma
    • 24. Abnormal free T4
    • 25. Patients with serious infection
Evaluation of Superiority of Valsartan+Celecoxib+Metformin Over Metformin Alone in Type 2 Diabetes Patients

Location Details

NCT03686657

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Locations

Not yet recruiting

United States, New York

Albany Medical College

Albany, New York, United States, 12206