AZD5004 for Type 2 Diabetes

(SOLSTICE Trial)

Not currently recruiting at 111 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: Any Age

Sex: Any

Trial Phase: Phase 2

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 This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD5004 for individuals with type 2 diabetes. The goal is to determine if AZD5004 is safe and effective compared to a placebo and another diabetes drug, Semaglutide. Participants will receive varying doses of AZD5004 or a placebo, while one group will receive Semaglutide. The trial seeks adults who have had type 2 diabetes for at least six months and manage it with diet, exercise, metformin, or an SGLT2 inhibitor. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of a potentially effective new diabetes treatment.

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.

Is there any evidence suggesting that AZD5004 is likely to be safe for humans?

Research has shown that AZD5004 is generally safe, with side effects similar to other drugs in its class, known as GLP-1 receptor agonists. Early studies suggest that people tolerate AZD5004 well, and no major safety concerns have emerged. While these findings are encouraging, further research is needed to fully understand the safety of AZD5004. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for type 2 diabetes?

Unlike the standard treatments for type 2 diabetes, which often include medications like metformin or insulin that manage blood sugar levels, AZD5004 is an investigational drug that might offer a new approach. While the exact mechanism of AZD5004 isn't detailed in the trial information, researchers are generally excited because it could target diabetes differently, potentially offering better control or fewer side effects. Additionally, the trial includes an arm using semaglutide, a current treatment, as an active comparator, which could highlight AZD5004's unique benefits or effectiveness compared to existing options. This research could potentially lead to more personalized treatment plans for patients.

What evidence suggests that AZD5004 might be an effective treatment for type 2 diabetes?

Research has shown that AZD5004, which participants in this trial may receive, is a promising treatment for type 2 diabetes. It helps the body release more insulin when blood sugar levels are high, thereby lowering blood sugar. Previous studies suggest that similar treatments effectively manage type 2 diabetes and can also aid in weight loss. Early trial results indicated that AZD5004 can improve blood sugar control, making it an exciting option for those seeking to manage their type 2 diabetes more effectively. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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

Body mass index of ≥ 23 kg/m2

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

My HbA1c is between 7.0% and 10.5%, managed with diet, exercise, metformin, or an SGLT2 inhibitor.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• AZD5004

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39495140/

Non-clinical and first-in-human characterization of ... These data support continued development of ECC5004 as a potential therapy for T2DM and overweight or obesity. Clinical trial registration: ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06579105

NCT06579105 | Efficacy, Safety, and Tolerability of Once ... Efficacy, Safety, and Tolerability of Once Daily Oral Administration of AZD5004 Versus Placebo for 26 Weeks in Adults With Type 2 Diabetes Mellitus.

3. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.16047

Non‐clinical and first‐in‐human characterization of ECC5004 ... Aims GLP-1 receptor agonists (GLP-1 RAs) are proven therapies for type 2 diabetes mellitus (T2DM) and overweight or obesity.

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7261C00001

SOLSTICE This is a Phase IIb, randomised, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy, safety and tolerability of AZD5004 in adults ...

5. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2023/agreement-with-eccogene-for-clinical-stage-glp-1ra.html

AstraZeneca licenses novel agent for the treatment of ... ECC5004 is a once daily, low dose, small molecule GLP-1RA which is currently in a US Phase I clinical trial in healthy participants and patients ...