AZD5004 for Type 2 Diabetes

(SOLSTICE Trial)

Recruiting in Palo Alto (17 mi)

+102 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AstraZeneca

Must be taking: Metformin, SGLT2 inhibitors

Must not be taking: Weight loss medications

Disqualifiers: Type 1 diabetes, Retinopathy, Pancreatitis, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase IIb, randomised, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy, safety and tolerability of AZD5004 in adults with type 2 diabetes mellitus, compared to placebo and active comparator.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it allows participants who are on a stable dose of metformin or an SGLT2 inhibitor. It seems you can continue these medications if they are stable.

What makes the drug AZD5004 unique for treating type 2 diabetes?

AZD5004, also known as ECC5004, is unique because it may offer a novel approach to managing type 2 diabetes, potentially involving a different mechanism of action or administration compared to existing treatments like metformin, sulfonylureas, and thiazolidinediones. However, specific details about its uniqueness are not provided in the available research. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with type 2 diabetes who have not achieved adequate blood sugar control. Participants should be able to take oral medication and commit to the study for 26 weeks. Specific medical conditions or treatments that could interfere with the study are reasons for exclusion.

Inclusion Criteria

I am 18 years old or older.

Body mass index of ≥ 23 kg/m2

Stable self-reported body weight for 3 months prior to randomization (+/- 5% body weight change)

Exclusion Criteria

More than one episode of severe hypoglycemia within 6 months prior to screening, or history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms

I have had pancreatitis before.

I have taken weight loss medication in the past 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD5004 or placebo for 26 weeks to evaluate efficacy, safety, and tolerability

26 weeks

Visits at baseline, weeks 4, 12, 16, and 26

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AZD5004 (Anti-diabetic agent)

Trial Overview The trial tests a new once-daily pill, AZD5004, against a placebo (a dummy pill) and Semaglutide, an existing diabetes medication. The goal is to see if AZD5004 is effective in controlling blood sugar levels over a period of 26 weeks.

Participant Groups

Group I: Arm 6 Experimental Treatment 1 Intervention

Participants will receive xx mg once daily dose of AZD5004

Group II: Arm 5 Experimental Treatment 1 Intervention

Participants will receive xx mg once daily dose of AZD5004

Group III: Arm 4 Experimental Treatment 1 Intervention

Participants will receive xx mg once daily dose of AZD5004

Group IV: Arm 3 Experimental Treatment 1 Intervention

Participants will receive xx mg once daily dose of AZD5004

Group V: Arm 2 Experimental Treatment 1 Intervention

Participants will receive xx mg once daily dose of AZD5004

Group VI: Arm 1 Experimental Treatment 1 Intervention

Participants will receive xx mg once daily dose of AZD5004

Group VII: Arm 7 Active Control 1 Intervention

Participants will receive once daily dose of Semaglutide as active comparator

Group VIII: Arm 8 Placebo Group 1 Intervention

Participants will receive matching placebo for each AZD5004 arm

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Research Site Mobile, AL

Research Site Vestavia Hills, AL

Research Site Ocoee, FL

Research Site Savannah, GA

More Trial Locations

Who Is Running the Clinical Trial?

AstraZeneca Lead Sponsor

References

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

The metabolic effects of troglitazone in patients with diabetes and end-stage renal disease. [2018] Thiazolidinediones (TZD) are effective agents for the treatment of hyperglycemia, and appear ideal in diabetic patients with progressive or end-stage renal disease because of its predominant hepatic clearance. Troglitazone, the first available TZD for clinical use, was withdrawn due to safety concerns; however, studies completed with this agent can provide a better understanding of the class effect of TZDs. This study was an open-label, controlled clinical trial examining the safety and efficacy of troglitazone in type 2 diabetic patients with end-stage renal disease (ESRD). Twelve subjects were randomized to parallel study groups and treated for 6 mo with or without troglita-zone at a maximum dose of 600 mg/d in addition to continuing their previous diabetes medications (insulin or sulfonylurea). The results showed no significant differences in glycemic control with or without troglit-azone treatment for 6 mo. However, there was a significant reduction in insulin dosage with troglitazone treatment (22.9 +/- 7.3 units/d) than without troglita-zone treatment (54 +/- 12.9 units/d) (p

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

Novel sulfonylurea and non-sulfonylurea drugs to promote the secretion of insulin. [2019] The onset of type 2 diabetes is characterized by two determining factors: the insufficient ability to secrete insulin and/or the resistance to its biological action. Although in a very small proportion of individuals, one of those two metabolic abnormalities is the leading cause of diabetes, in most subjects, the coexistence of both appears to be necessary for the clinical manifestation of diabetes. Current biomedical research continues to clarify the relative contributions of these defects to the pathogenesis of type 2 diabetes, and novel pharmacological agents are specifically designed to correct either the impaired insulin secretory activity or the resistance to the action of insulin. The aim of this article is to provide a critical review of new sulfonylurea and non-sulfonylurea drugs that have been recently introduced for the treatment of diabetes, as well as drugs that are still under investigation and are likely to be made available in the near future.

3. England pubmed.ncbi.nlm.nih.gov

A review of the efficacy and safety of oral antidiabetic drugs. [2022] Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes.

4. England pubmed.ncbi.nlm.nih.gov

Zucker Diabetic-Sprague Dawley (ZDSD) rat: Type 2 diabetes translational research model. [2022] What is the topic of this review? The Zucker Diabetic-Sprague Dawley (ZDSD) rat is in the early adoption phase of use by researchers in the fields of diabetes, including prediabetes, obesity and metabolic syndrome. It is essential that physiology researchers choose preclinical models that model human type 2 diabetes appropriately and are aware of the limitations on experimental design. What advances does it highlight? Our review of the scientific literature finds that although sex, age and diets contribute to variability, the ZDSD phenotype and disease progression model the characteristics of humans who have prediabetes and diabetes, including co-morbidities.

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

In vivo prevention of hyperglycemia also prevents glucotoxic effects on PDX-1 and insulin gene expression. [2022] Chronic exposure of pancreatic islet beta-cell lines to supraphysiologic glucose concentrations causes defects in insulin gene expression and insulin secretion. To determine whether these in vitro phenomena have pathophysiologic relevance in vivo, we studied the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. The ZDF animals had relatively higher levels of glycemia and islet insulin mRNA at 6 weeks of age than age-matched Zucker lean control (ZLC) rats. As glycemia increased in 12- and 16-week-old ZDF rats, we observed decrements in glucose-induced insulin secretion during static incubations of pancreatic islets and in insulin mRNA levels, PDX-1 mRNA levels, and PDX-1 protein binding to the insulin promoter compared with age-matched ZLC rats and 6-week-old ZDF rats. To determine whether normalization of blood glucose levels would prevent these defects, ZDF rats were treated with troglitazone beginning at 6 weeks of age. Troglitazone prevented ZDF rats from becoming hyperglycemic and preserved glucose-induced insulin responses. Furthermore, troglitazone-treated ZDF animals had greater levels of insulin and PDX-1 mRNAs compared with untreated ZDF animals of the same ages at 12 and 16 weeks. Our results demonstrate that chronic and progressive hyperglycemia resulting from type 2 diabetes in ZDF rats is associated with loss of insulin and PDX-1 mRNAs and loss of glucose-stimulated insulin secretion. Prevention of hyperglycemia prevented the associated defects in insulin and PDX-1 gene expression and improved insulin secretion. These findings provide the first in vivo evidence that prevention of progressive hyperglycemia in a model of type 2 diabetes preserves insulin and PDX-1 gene expression.