AZD5004 for Type 2 Diabetes

(SOLSTICE Trial)

Recruiting at103 trial 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}

Research Team

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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a 6-month study involving 12 type 2 diabetic patients with end-stage renal disease, troglitazone treatment did not significantly improve overall glycemic control compared to control, but it did allow for a significant reduction in insulin dosage.

The study found that troglitazone was safe for patients requiring dialysis, with no observed weight changes or elevated liver enzyme levels, supporting the use of thiazolidinediones in diabetic patients with renal failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The metabolic effects of troglitazone in patients with diabetes and end-stage renal disease. Mohideen, P., Bornemann, M., Sugihara, J., et al.[2018]

Type 2 diabetes is primarily caused by two factors: insufficient insulin secretion and insulin resistance, with most individuals experiencing both issues for the disease to manifest.

The article reviews new and emerging pharmacological agents, including sulfonylureas and non-sulfonylureas, aimed at addressing these metabolic defects to improve diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel sulfonylurea and non-sulfonylurea drugs to promote the secretion of insulin. Perfetti, R., Ahmad, A.[2019]

Dipeptidyl peptidase-IV (DPP-4) inhibitors are a newer class of oral medications for type 2 diabetes that offer moderate efficacy and a low side-effect profile, making them a good alternative when metformin causes gastrointestinal issues or when sulfonylureas lead to hypoglycemia or weight gain.

Other newer agents like meglitinide analogs and α-glucosidase inhibitors have limitations such as frequent dosing and gastrointestinal side effects, while bile-acid sequestrants and bromocriptine have lower efficacy in reducing HbA(1c) but a low risk of hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the efficacy and safety of oral antidiabetic drugs. Stein, SA., Lamos, EM., Davis, SN.[2022]

The Zucker Diabetic-Sprague Dawley (ZDSD) rat is a promising preclinical model for studying type 2 diabetes (T2D) as it accurately reflects the disease progression and associated complications seen in humans, including obesity and cardiovascular issues.

Research shows that ZDSD rats develop prediabetes and progress to diabetes, with significant health issues such as hypertension and impaired wound healing, making them a valuable tool for testing new treatments for T2D.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zucker Diabetic-Sprague Dawley (ZDSD) rat: Type 2 diabetes translational research model. Wang, AN., Carlos, J., Fraser, GM., et al.[2022]

In a study using Zucker diabetic fatty (ZDF) rats, chronic high blood sugar levels were linked to decreased insulin and PDX-1 gene expression, leading to impaired insulin secretion, highlighting the negative impact of prolonged hyperglycemia in type 2 diabetes.

Treatment with troglitazone starting at 6 weeks of age successfully prevented hyperglycemia in ZDF rats, which in turn preserved insulin and PDX-1 mRNA levels and improved insulin secretion, demonstrating the potential for early intervention in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo prevention of hyperglycemia also prevents glucotoxic effects on PDX-1 and insulin gene expression. Harmon, JS., Gleason, CE., Tanaka, Y., et al.[2022]

References

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

The metabolic effects of troglitazone in patients with diabetes and end-stage renal disease. [2018]

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

Novel sulfonylurea and non-sulfonylurea drugs to promote the secretion of insulin. [2019]

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

A review of the efficacy and safety of oral antidiabetic drugs. [2022]

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

Zucker Diabetic-Sprague Dawley (ZDSD) rat: Type 2 diabetes translational research model. [2022]

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]