Modified Release Glipizide for Gastrointestinal Absorption Study

Overseen By Zerick Dill, MS

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

Trial Summary

What is the purpose of this trial?

In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. 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 Glipizide by direct sampling of stomach and small intestinal luminal content, blood, urine and feces. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution.

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.

What data supports the effectiveness of the drug Glipizide for gastrointestinal absorption?

Research shows that Glipizide, when taken orally, is highly effective in lowering blood sugar levels in patients with type 2 diabetes. It has a rapid onset of action and maintains its effectiveness over time, as seen in studies where it significantly reduced blood glucose levels and increased insulin secretion. ^{1 2 3 4 5}

Is modified release glipizide generally safe for humans?

Studies on glipizide, including its modified release form, have shown it to be generally safe in humans, with its main use being to lower blood sugar in people with type 2 diabetes. The safety profile is consistent across different formulations, and no major safety concerns have been reported in the studies reviewed. ^{1 3 5 6 7}

How is the modified release glipizide drug different from other diabetes drugs?

Modified release glipizide is unique because it uses a special system to release the drug slowly in the gastrointestinal tract, allowing for once-daily dosing and more stable blood sugar control throughout the day compared to immediate-release versions. ^{1 3 5 8 9}

Research Team

Arsalan Zafar Iqbal, MBBS

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Bioavailability, pharmacokinetics and effects of glipizide in type 2 diabetics. [2018]

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

Bioavailability of glipizide and its effect on blood glucose and insulin levels in patients with non-insulin-dependent diabetes. [2019]

3. United States 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. [2022]

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

In vitro-in vivo correlation for gliclazide immediate-release tablets based on mechanistic absorption simulation. [2021]

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

Comparative efficacy of a once-daily controlled-release formulation of glipizide and immediate-release glipizide in patients with NIDDM. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Development of a robust once-a-day glipizide matrix system. [2013]

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

Comparative pharmacokinetics studies of immediate- and modified-release formulations of glipizide in pigs and dogs. [2013]

8. England 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. [2022]

9. China pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics and bioavailability of glipizide capsules]. [2013]