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

NCT03686657 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TriGlytza (RK-01) Prototype
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes; High Blood Pressure; Arthritis; Obesity

Keywords

Diabetes; Obesity; FPG; Beta cell function index; HbA1c; Atherogenic index

Outcome Measures

Primary Outcomes (4)

• 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.

  Baseline and 26 weeks

• 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.

  Baseline and 26 weeks

• 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

  Baseline and 26 weeks

• 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

  Baseline and 26 weeks

Secondary Outcomes (13)

• Change in glycosylated Hemoglobin (HbA1c) to <7.0%

  Baseline and 26 weeks

• Change from baseline in Body weight

  Baseline and 26 weeks

• Change from baseline in fasting plasma glucose

  Baseline and 26 weeks

• Change from baseline in Beta-cell function Index

  Baseline and 26 weeks

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

  Baseline and 26 weeks

Study Arms (4)

Healthy adults with NGT

NO INTERVENTION

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

Metformin-Drug naive patients & Patients with inadequate glycemic control with Metformin

ACTIVE COMPARATOR

Patients receive metformin once daily

Drug: Metformin

RK-01 Low

EXPERIMENTAL

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

Drug: Val, Cel and Met XR Low

RK-01 High

EXPERIMENTAL

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

Drug: Val, Cel and Met XR High

Interventions

Metformin DRUG

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

Also known as: Glucophage, Glucophage XR

Metformin-Drug naive patients & Patients with inadequate glycemic control with Metformin

Val, Cel and Met XR Low DRUG

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.

Also known as: Diovan, Celebrex, Glucophage XR, RK-01

RK-01 Low

Val, Cel and Met XR High DRUG

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.

Also known as: Diovan, Celebrex, Glucophage XR, RK-01

RK-01 High

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• Hour OGTT ≥200 mg/dL
• FPG ≥140 mg/dL
• BMI ≥30
• Impaired first phase and second phase of insulin secretion

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• ARKAY Therapeutics: lead
• Albany Medical College: collaborator
• Myopharm Limited: collaborator

Study Sites (1)

Albany Medical College

Albany, New York, 12206, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension; Arthritis; Obesity; Diabetes Mellitus

Interventions

Metformin; Valine; Carboxylesterase; Valsartan; Celecoxib

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Joint Diseases; Musculoskeletal Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Carboxylic Ester Hydrolases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles

Study Officials

• Ravi Kumar, Ph.D.

  ARKAY Therapeutics

  STUDY DIRECTOR

Central Study Contacts

Karinza Phoenix

CONTACT

+61 498505321; kphoenix@myopharm.com

George Tochas, Ph.D.

CONTACT

gtachas@myopharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2018
• First Posted: September 27, 2018
• Study Start: October 10, 2025
• Primary Completion (Estimated): November 26, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: June 3, 2025

Record last verified: 2025-05

Locations

US (1)