GS-4571 for Type 2 Diabetes

Recruiting in San Antonio (>99 mi)

+1 other location

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Gilead Sciences

Must be taking: Metformin

Must not be taking: GLP-1RAs, Systemic steroids

Disqualifiers: Serious illness, Pancreatitis, Cardiac disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to learn more about the study drug, GS-4571, and how safe it is in 3 groups, i) Healthy participants, ii) Healthy non-diabetic obese participants, and iii) Non-obese participants with Type 2 Diabetes Mellitus (T2DM). The primary objectives of this study are: * To characterize the pharmacokinetics (PK) of GS-4571 following single and multiple ascending oral doses of GS-4571. * To evaluate the effectiveness of a representative gastric acid-reducing agent (proton pump inhibitor (PPI), omeprazole) on the PK of GS-4571. * To evaluate the effectiveness of concomitant food intake on the PK of GS-4571. * To evaluate the safety and tolerability of single and multiple ascending oral doses of GS-4571.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used certain medications like GLP-1RAs, systemic steroids, or immunosuppressants within 6 months before the trial. If you're on metformin for Type 2 Diabetes, you can continue using it.

Is GS-4571 (also known as Omeprazole) generally safe for humans?

Omeprazole has been studied in over 19,000 people and is generally safe, with mild side effects like nausea, dizziness, headache, and diarrhea. These side effects are usually temporary and don't require stopping the medication. Serious side effects are rare, and the overall incidence of side effects is low. ^{1 2 3 4 5}

How is the drug GS-4571 unique for treating type 2 diabetes?

GS-4571, which includes omeprazole, is unique because it may improve insulin secretion and glucose metabolism in type 2 diabetes, unlike traditional diabetes medications that primarily focus on lowering blood sugar levels. ^{1 6 7 8 9}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for healthy adults, non-diabetic obese individuals, and non-obese people with Type 2 Diabetes. Participants should have a stable body weight and meet specific BMI criteria: healthy (19-30 kg/m2), obese (30-45 kg/m2), diabetic (19-30 kg/m2). Diabetics can only be on diet/exercise or metformin, and must not have used GLP-1RA drugs recently.

Inclusion Criteria

Individuals will also be in good general health as determined by the investigator at the screening evaluation performed no more than 28 days prior to the scheduled first dose

I have never taken GLP-1RA drugs, or it's been 6 months since my last dose.

I am healthy with a BMI between 19 and 30, and no significant medical history.

Exclusion Criteria

Any condition that could lead to electrolyte disturbances (eg, eating disorder) in the opinion of the investigator

Any electrolyte disturbances identified at screening considered to be clinically significant in the opinion of the investigator (eg, hypokalemia, hypocalcemia, or hypomagnesemia)

Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with individual treatment, assessment, or compliance with the protocol. This would include acute pancreatitis, or history of pancreatitis, acute gallbladder disease, and renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes [with the exception of T2DM for individuals included in Part D only]), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single-ascending Dose (SAD) in Healthy Participants

Participants receive single ascending oral doses of GS-4571 to determine the maximum tolerated dose

1 day per cohort

5 visits (in-person)

Multiple Dose in Nonobese Participants With T2DM

Participants receive up to the highest dose of GS-4571 or placebo for 12 weeks

12 weeks

Weekly visits (in-person)

Food/PPI Effect in Healthy Participants

Participants receive GS-4571 and omeprazole to evaluate the effect of food and PPI on pharmacokinetics

5 days

2 visits (in-person)

Multiple-ascending Dose (MAD) in Nondiabetic Obese Participants

Participants receive multiple ascending doses of GS-4571 or placebo for 12 weeks

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• GS-4571 (Investigational Drug)
• Omeprazole (Proton Pump Inhibitor)

Trial Overview The study tests GS-4571's safety and how the body processes it after different doses. It also looks at how omeprazole (a stomach acid reducer) or eating food affects GS-4571 in the system. The drug is given orally to three groups: healthy individuals, obese without diabetes, and diabetics without obesity.

Participant Groups

Group I: Part D Multiple Dose in Nonobese Participants With T2DM Experimental Treatment 2 Interventions

Participants randomized in Cohort 11 will receive up to the highest dose of GS-4571 or PTM in T2DM, QD, in a non-fasting state for 12 weeks.

Group II: Part C Multiple-ascending Dose (MAD) in Nondiabetic Obese Participants Experimental Treatment 2 Interventions

Participants randomized in Cohorts 7-9 will be randomized to receive up to 4 escalating doses of GS-4571 or PTM QD for 12 weeks, as follows: * Cohort 7: Up to dose determined from Part A of GS-4571 or PTM in obese participants, QD, in a non-fasting state * Cohort 8: Up to 3-fold the Cohort 7 dose of GS-4571 or PTM in obese participants, QD, in a non-fasting state * Cohort 9: Up to 2-fold the Cohort 8 dose of GS-4571 or PTM in obese participants, QD, in a non-fasting state Cohort 10 is optional and will receive GS-4571 or PTM QD for 12 weeks in case it is opened for enrollment as follows: • Up to 2-fold the Cohort 9 dose of GS-4571 or PTM in obese participants, QD, in a non-fasting state.

Group III: Part B Food/PPI Effect in Healthy Participants Experimental Treatment 2 Interventions

Participants will be randomized into 2 sequence groups in Cohort 6 and will receive the highest dose found to be safe and well tolerated in Part A of GS-4571 and omeprazole. The two sequential groups will receive the following treatments: * Treatment A: Up to the highest single dose of GS-4571 evaluated in Part A, fasting. * Treatment B: Up to the highest single dose of GS-4571 evaluated in Part A, nonfasting (high-fat/high-calorie meal). * Treatment C: Omeprazole, once-daily (QD) for 5 days, fasting. * Treatment D: Omeprazole followed by up to the highest single dose of GS-4571 evaluated in Part A, 2 hours later, fasting.

Group IV: Part A Single-ascending Dose (SAD) in Healthy Participants Experimental Treatment 2 Interventions

Participants will be randomized into 5 dose escalating cohorts and will receive GS-4571 or placebo to match (PTM) GS-4571 on Day 1, to determine the maximum tolerated dose: * Cohort 1: Dose 1 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 2: Dose 2 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 3: Dose 3 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 4: Dose 4 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 5: Dose 5 GS-4571, administered orally as a single dose, in a fasting state.

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

In a Phase III study involving 239 patients with frequent GERD, Zegerid and Losec showed no significant difference in the median time to sustained heartburn relief, with both treatments taking around 60 minutes for Zegerid and 52 minutes for Losec.

However, Zegerid was found to provide sustained total relief within 0-30 minutes for significantly more patients compared to Losec, indicating a potentially faster onset of action despite overall similar efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec. Walker, D., Ng Kwet Shing, R., Jones, D., et al.[2020]

In a study involving 915 patients with gastroesophageal reflux disease (GERD), pantoprazole 40 mg provided significantly faster symptom relief compared to omeprazole 20 mg, with patients experiencing relief 2 days earlier.

After 6 weeks of treatment, both medications were well tolerated, and over 90% of patients in both groups reported being free from symptoms, indicating that pantoprazole is an effective option for GERD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Financial restrictions in health care systems could affect treatment quality of GERD-patients]. Gillessen, A., Schöffel, L., Naumburger, A.[2018]

Omeprazole, a new drug for treating acid-related diseases, was found to be prescribed at higher doses than the established daily recommendations, indicating its strong clinical use in hospitalized patients.

The study revealed that while omeprazole was appropriately prescribed for its intended use, its substitution for H2 receptor antagonists like cimetidine and ranitidine significantly increased drug costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omeprazole. A pharmaco-epidemiological study of its use in a university hospital. Burger, DM., Hekster, YA., Hopman, WP., et al.[2019]

In a study of 17 patients with duodenal ulcers, omeprazole (Losec) demonstrated a high healing rate, with 94% of ulcers healed after 4 weeks of treatment, significantly improving patient outcomes (P < 0.001).

Omeprazole also effectively eliminated Helicobacter pylori in 11 out of 16 patients, indicating its role in reducing chronic gastritis and improving overall gastric health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of omeprazole on healing of duodenal ulcers, Helicobacter pylori and gastritis]. Zelenková, J., Soucková, A., Drábek, J., et al.[2020]

A review of over 19,000 individuals showed that omeprazole has a low incidence of mild and transient adverse events, such as nausea and headache, which typically do not require dose adjustments or discontinuation of therapy.

No serious drug-related adverse events were found in patients with renal insufficiency or severe liver failure, and long-term use of omeprazole did not lead to significant histological changes in gastric cells, indicating its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical safety of omeprazole. Sölvell, L.[2018]

In a study of 174 type 2 diabetes patients with acid peptic disease, omeprazole therapy led to significant improvements in symptoms, with 98.2% reporting relief from abdominal pain and complete resolution of flatulence and loss of appetite in all affected patients.

Omeprazole was found to be well tolerated, indicating it is a safe and effective treatment option for managing acid peptic disease in patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Evidence-Based Retrospective Study for the Management of Acid Peptic Disease With Omeprazole, a Proton Pump Inhibitor, in Indian Patients With Type 2 Diabetes Mellitus (PRIDE-1). Saboo, B., Mulwani, N., Petare, AU., et al.[2023]

A case-control study involving 20,940 patients with type 2 diabetes and 20,940 controls found that higher doses of proton pump inhibitors (PPIs) are associated with an increased risk of developing type 2 diabetes mellitus (T2DM).

Specifically, patients taking higher cumulative doses of PPIs showed a dose-dependent increase in risk, with odds ratios ranging from 1.20 to 1.34, indicating that even commonly used PPIs like pantoprazole, lansoprazole, and omeprazole may contribute to this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Dependent Proton Pump Inhibitor Exposure and Risk of Type 2 Diabetes: A Nationwide Nested Case-Control Study. Kuo, HY., Liang, CS., Tsai, SJ., et al.[2023]

In a study of 732 GERD patients, those with type 2 diabetes mellitus (DM) had a significantly higher rate of proton pump inhibitor (PPI) treatment failure, particularly among obese individuals.

Among GERD patients with type 2 DM, factors such as female sex and the presence of other health conditions were linked to a higher likelihood of PPI failure, while the duration of diabetes and type of diabetes medication did not impact treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between type 2 diabetes mellitus and failure to proton pump inhibitor treatment in gastroesophageal reflux disease. Hershcovici, T., Jha, LK., Gadam, R., et al.[2022]

In a study involving 41 patients with type 2 diabetes, treatment with esomeprazole for 12 weeks did not lead to any significant changes in insulin secretion or glycemic control, as measured by insulin levels and HbA1c.

Esomeprazole treatment resulted in a significant increase in gastrin levels but did not affect cardiovascular risk markers, while the placebo group showed improvements in blood pressure and a decrease in insulin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 12 weeks' treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study. Hove, KD., Brøns, C., Færch, K., et al.[2022]

References

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

Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

[Financial restrictions in health care systems could affect treatment quality of GERD-patients]. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Omeprazole. A pharmaco-epidemiological study of its use in a university hospital. [2019]

4. Czech Republic pubmed.ncbi.nlm.nih.gov

[The effect of omeprazole on healing of duodenal ulcers, Helicobacter pylori and gastritis]. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The clinical safety of omeprazole. [2018]

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

An Evidence-Based Retrospective Study for the Management of Acid Peptic Disease With Omeprazole, a Proton Pump Inhibitor, in Indian Patients With Type 2 Diabetes Mellitus (PRIDE-1). [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Dose-Dependent Proton Pump Inhibitor Exposure and Risk of Type 2 Diabetes: A Nationwide Nested Case-Control Study. [2023]

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

The relationship between type 2 diabetes mellitus and failure to proton pump inhibitor treatment in gastroesophageal reflux disease. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Effects of 12 weeks' treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study. [2022]