GS-4571 for Type 2 Diabetes
Recruiting in Palo Alto (17 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.12345
Research Team
GS
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.
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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
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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 OverviewThe 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
4Treatment groups
Experimental Treatment
Group I: Part D Multiple Dose in Nonobese Participants With T2DMExperimental Treatment2 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 ParticipantsExperimental Treatment2 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 ParticipantsExperimental Treatment2 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 ParticipantsExperimental Treatment2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
ICON Early Phase Services, LLCSan Antonio, TX
ICONSalt Lake City, UT
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Who Is Running the Clinical Trial?
Gilead Sciences
Lead Sponsor
Trials
1150
Patients Recruited
878,000+
Findings from Research
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]
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]
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]
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
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]
[Financial restrictions in health care systems could affect treatment quality of GERD-patients]. [2018]
Omeprazole. A pharmaco-epidemiological study of its use in a university hospital. [2019]
[The effect of omeprazole on healing of duodenal ulcers, Helicobacter pylori and gastritis]. [2020]
The clinical safety of omeprazole. [2018]
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]
Dose-Dependent Proton Pump Inhibitor Exposure and Risk of Type 2 Diabetes: A Nationwide Nested Case-Control Study. [2023]
The relationship between type 2 diabetes mellitus and failure to proton pump inhibitor treatment in gastroesophageal reflux disease. [2022]
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]