Modified Release Glipizide for Gastrointestinal Absorption Study

Overseen By Cathrin Ring

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Michigan

Must not be taking: Aspirin, Blood thinners

Disqualifiers: Cardiovascular disease, Diabetes, Allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how a modified version of the drug Glipizide, used to treat type 2 diabetes, dissolves and absorbs in the stomach and intestines. Participants will take a special formulation of Glipizide along with Rifaximin to help researchers understand how these drugs behave in the body. This information may lead to better drug designs for individuals with conditions affecting drug absorption. Those who can swallow a multivitamin pill and have no serious allergies or major health issues affecting the stomach or intestines might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

Yes, participants must stop taking any medications and/or supplements, both prescription and over-the-counter, one week before starting the study and throughout the study, except for certain birth control methods.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that glipizide is well absorbed by the body and is generally safe for adults. Studies indicate that the most common side effects include mild stomach issues, such as nausea and diarrhea. Rarely, it may cause a liver issue called cholestatic jaundice, which can cause yellowing of the skin and eyes. Glipizide is already FDA-approved for treating type 2 diabetes, indicating its safety for many individuals with that condition. These points may help prospective trial participants understand what to expect with glipizide.

The trial also includes a small dose of rifaximin, an antibiotic often used for gut-related issues. Rifaximin is generally well-tolerated, with mild stomach upset as the most common side effect. Both medications have been used separately and are considered safe when used as directed. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard release of Glipizide for managing blood sugar levels, this modified-release version is designed to enhance gastrointestinal absorption. Researchers are excited because it includes a stable isotope of Glipizide, which allows for more precise tracking of how the drug is absorbed and utilized by the body. This could lead to a more consistent and effective management of blood sugar levels compared to current options, potentially resulting in fewer side effects and more stable glucose control for patients.

What evidence suggests that this trial's treatments could be effective for gastrointestinal absorption?

Studies have shown that glipizide, particularly in its modified or extended-release form, helps manage blood sugar levels in people with type 2 diabetes. It can significantly lower fasting blood sugar levels by 57 to 74 mg/dl and reduce HbA1c (which measures average blood sugar over time) by 1.50 to 1.82 percentage points. Research indicates that glipizide-GITS, a special form that releases the medicine slowly, is more effective than the immediate-release version in controlling blood sugar spikes after meals. This suggests that modified-release glipizide can improve overall blood sugar control and better manage diabetes symptoms.

In this trial, participants will receive a single dose of modified-release glipizide to study its gastrointestinal absorption. ^{6 7 8 9 10}

Who Is on the Research Team?

Cathrin Ring

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

Healthy adults aged 18-55 with a BMI of 18.5 to 35 kg/m2 who can swallow a pill similar to SmartPill and provide informed consent are eligible for this trial. Exclusions include those with recent surgeries, hypersensitivities, diabetes, abnormal lab values, dysphagia, substance use before visits, certain medication usage including blood thinners and electro-mechanical medical devices.

Inclusion Criteria

I have recently lost my sense of smell or taste.

I can understand and agree to the study details on my own.

I can swallow a pill the size of a multivitamin.

Exclusion Criteria

Use of an implanted or portable electro-mechanical medical device such as a cardiac pacemaker or infusion pump.

I have had radiation therapy to my abdomen.

History and/or presence of hypersensitivity to any of the study drugs or the products' excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Dosing

Participants receive a single dose of Glipizide and Rifaximin with glucose solution, followed by collection of fluids from stomach and GI tract through intubation, blood, urine, and feces to measure glipizide concentrations.

78 hours

1 visit (in-patient)

Follow-up

Participants are monitored for safety and effectiveness after the dosing phase.

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Glipizide

Trial Overview The study tests how well different modified release forms of Glipizide dissolve in the GI tract and get absorbed into the body by sampling stomach/intestinal contents and bodily fluids. It also collects data on GI physiology using an electronic pill called SmartPill.

How Is the Trial Designed?

Group I: G.I Intubation Experimental Treatment 4 Interventions

Single dose of Glipizide (5 mg modified-release tablet) and Rifaximin (200 mg tablet) administered with 200 mL of 20% glucose solution in water + 1 mg of the stable isotope Glipizide (13C6-Glipizide) with 40 ml of 14% glucose solution in water. A 'Stable isotope' means a heavier version of the drug that is not radioactive.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Published Research Related to This Trial

In a study involving seven patients with non-insulin-dependent diabetes, glipizide showed consistent bioavailability, peaking in plasma within 1.2-1.8 hours and having a half-life of 2.5-3.2 hours over 15 days of administration.

The hypoglycemic effect of glipizide was significantly greater on day 15 compared to day 1, indicating improved efficacy over time, even when drug levels were undetectable in plasma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of glipizide and its effect on blood glucose and insulin levels in patients with non-insulin-dependent diabetes. Peterson, CM., Sims, RV., Jones, RL., et al.[2019]

In a study involving six male pigs, the modified-release (MR) formulation of glipizide showed a delayed time to reach maximum concentration (t(max)) compared to the immediate-release (IR) formulation, indicating different absorption profiles between the two formulations.

The pharmacokinetics of glipizide in pigs were consistent with human clinical data, suggesting that pigs are a suitable preclinical model for evaluating the efficacy and safety of pharmaceutical formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetics studies of immediate- and modified-release formulations of glipizide in pigs and dogs. Kulkarni, R., Yumibe, N., Wang, Z., et al.[2013]

The study successfully developed a drug-specific absorption model for gliclazide using advanced gastrointestinal simulation technology, which accurately predicted its oral absorption based on clinical data.

The findings suggest that for gliclazide immediate-release tablets, a dissolution specification of over 85% within 60 minutes is necessary to meet 'biorelevant' acceptance criteria, ensuring effective drug release in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro-in vivo correlation for gliclazide immediate-release tablets based on mechanistic absorption simulation. Grbic, S., Parojcic, J., Ibric, S., et al.[2021]

In a study involving 132 patients with non-insulin-dependent diabetes mellitus, controlled-release glipizide (glipizide-GITS) was found to be significantly more effective than immediate-release glipizide in lowering fasting plasma glucose levels after 8 weeks of treatment.

Glipizide-GITS not only maintained effective drug concentrations over 24 hours but also achieved better glucose control with lower insulin and C-peptide levels, indicating an improvement in insulin sensitivity compared to the immediate-release formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of a once-daily controlled-release formulation of glipizide and immediate-release glipizide in patients with NIDDM. Berelowitz, M., Fischette, C., Cefalu, W., et al.[2022]

Glipizide, when administered either intravenously or orally, showed rapid distribution and a short elimination half-life of 2 to 4 hours, indicating it acts quickly in the body.

The drug demonstrated 100% gastrointestinal bioavailability, meaning it is fully absorbed when taken orally, and effectively reduced blood glucose levels in all type 2 diabetic patients studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability, pharmacokinetics and effects of glipizide in type 2 diabetics. Wåhlin-Boll, E., Almér, LO., Melander, A.[2018]

The extended-release glipizide GITS significantly reduced fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels in patients with non-insulin dependent diabetes mellitus (NIDDM), with maximal efficacy observed at doses of 20 mg for FPG and 5 mg for HbA1c, based on a study involving 347 patients over 16 weeks.

Glipizide GITS was found to be safe and well-tolerated, with only 11 patients experiencing hypoglycemia, and it did not cause weight gain or negatively affect lipid levels, making it a suitable option for diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. The Glipizide Gastrointestinal Therapeutic System Study Group. Simonson, DC., Kourides, IA., Feinglos, M., et al.[2022]

Gliclazide-modified release (MR) demonstrated similar efficacy to standard gliclazide in reducing HbA1c levels in type 2 diabetic patients, with both treatments achieving a significant decrease of -1.6% over the study period.

Gliclazide MR showed a better trend in improving fasting plasma glucose levels compared to gliclazide, and both formulations had comparable safety profiles, with very few mild hypoglycemic episodes reported, suggesting that once-daily dosing may enhance patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized, multicentre study of the efficacy and safety of gliclazide-modified release in the treatment of Chinese type 2 diabetic patients. Lu, CH., Chang, CC., Chuang, LM., et al.[2022]

In a study involving 8 healthy male volunteers, glipizide showed a relative bioavailability of 109.9% when taken in capsule form compared to tablet form, indicating that the capsule may be absorbed more effectively.

The pharmacokinetics of glipizide were assessed using high performance liquid chromatography, providing detailed concentration-time data for both capsule and tablet preparations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics and bioavailability of glipizide capsules]. Chen, QC., Yang, CQ., Chao, CH., et al.[2013]

The new hydroxypropylmethylcellulose (HPMC) based modified release formulation of glipizide (10 mg) demonstrated consistent drug release profiles even with compositional changes of up to +/-20% w/w and halving the drug dose, indicating robustness in its design.

The study found that the drug release mechanism is primarily influenced by hydration and erosion kinetics, suggesting that the formulation can be reliably scaled up while meeting FDA guidelines for post-approval changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a robust once-a-day glipizide matrix system. Jamzad, S., Fassihi, R.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05159427

Pharmacokinetic Study of Single-Dose Modified Release ... The purpose of this clinical study is to evaluate the in vivo drug dissolution and systemic absorption of modified release formulations of the BCS Class II drug ...

2. metabolismjournal.com metabolismjournal.com/article/S0026-0495(22)00210-4/fulltext

Pharmacotherapy of type 2 diabetes: An update and future ... AGIs can be used as monotherapy but are not first line due to their relatively low efficacy, GI side effects, and cost. Thus, they are mainly ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9096986/

Efficacy, safety, and dose-response characteristics ... Results: All doses of glipizide GITS in both trials produced significant reductions from placebo in FPG (range -57 to -74 mg/dl) and HbA1c (range -1.50 to -1.82 ...

4. researchgate.net researchgate.net/publication/11329217_Pharmacokinetics_and_Pharmacodynamics_of_Extended-Release_Glipizide_GITS_Compared_with_Immediate-Release_Glipizide_in_Patients_with_Type_II_Diabetes_Mellitus

Pharmacokinetics and Pharmacodynamics of Extended ... This study was designed to compare the pharmacokinetic and short-term pharmacodynamic profile of extended-release glipizide GITS (Glucotrol ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/7882817/

Comparative efficacy of a once-daily controlled-release ... Conclusions: Glipizide-GITS was significantly more effective than immediate-release glipizide in reducing FPG levels. Both formulations reduced postprandial ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/017783s019lbl.pdf

glipizide tablet Roerig GLUCOTROL - accessdata.fda.gov Gastrointestinal absorption of GLUCOTROL in man is uniform, rapid, and essentially complete. ... Safety and effectiveness in children have not been established.

7. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Glipizide

Glipizide | C21H27N5O4S | CID 3478 - PubChem - NIH The most common adverse reactions are gastrointestinal and include nausea and diarrhea. In rare cases, cholestatic jaundice may result from glipizide therapy, ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/020329Orig1s035lbl.pdf

GLUCOTROL XL® (glipizide) extended release tablets, for ... Absorption. The absolute bioavailability of glipizide was 100% after single oral doses in patients with type 2 diabetes mellitus. Beginning 2 to.

9. labeling.pfizer.com labeling.pfizer.com/ShowLabeling.aspx?id=14648

Glucotrol XL Tablets 5mg and 10 mg Administration of glipizide GITS with food has no effect on the 2 to 3 hour lag time in drug absorption.

10. medcentral.com medcentral.com/drugs/monograph/10094-384060/glipizide-oral

Glipizide: uses, dosing, warnings, adverse events, ... Preliminary data suggest that glipizide may reduce the rate and/or extent of absorption of concomitantly administered oral xylose in type 2 diabetic patients.