Pharmacokinetic Study of Single-Dose Modified Release Glipizide in Healthy Volunteers

Open-Label, Randomized, Pharmacokinetic Study of Single-Dose Modified Release Glipizide in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Human Gastrointestinal Physiology Data
• Intervention / Treatment: Drug: Glucotrol XL 5Mg Extended-Release Tablet; Drug: Glipizide ER 5 MG 24 HR Extended Release Oral Tablet; Drug: Rifaximin 200Mg Tab; Drug: 13C6-Glipizide

Detailed Description

This is an in vivo study designed to acquire human gastrointestinal (GI) physiology data from healthy subjects which are necessary for mechanistic absorption model development. Each subject will be asked to complete a single dosing phase. The dosing phase will include collection of fluids from stomach and gastrointestinal (GI) tract through intubation (putting a GI tube from mouth into stomach and intestines), blood, urine and feces, and measure glipizide concentrations.

The objectives of this study are, as follows: Objective #1: To characterize the plasma, gastrointestinal fluid, urine, and feces concentrations of glipizide after oral administration of modified release formulations; Objective #2: To compare the pharmacokinetics of glipizide between the two modified release formulations; Objective #3: To collect gastrointestinal physiology data in volunteers receiving an oral MR formulation of glipizide. These in vivo results will be used to validate in vitro dissolution methods and to support computational and mathematical modeling efforts, in order to develop an oral drug product optimization process that may be applied to future drugs to maximize oral drug safety and efficacy.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female adults age 18 to 55 years with BMI ranging from 18.5 to 35 kg/m2 inclusive
2. Ability to independently provide an informed consent
3. Demonstrate the ability to swallow a multivitamin pill that mimics a SmartPill capsule
4. Negative serum pregnancy test (for women of child-bearing potential)

Exclusion Criteria:

1. Unable to independently provide an informed consent for themselves or mentally incapacitated.
2. Physical disability (including blindness or deafness) that requires special arrangements.
3. Significant clinical illness, including cardiovascular disease, neurological disease, organ failure, or malignancy in the opinion of the investigator
4. Any surgical procedure within 3 weeks prior to screening
5. History and/or presence of severe seasonal allergies or severe allergic diseases including drug allergies, food allergies and allergy against the SmartPill® device
6. History and/or presence of hypersensitivity to any of the study drugs or the products' excipients
7. History and/or presence of hypersensitivity to Sulfonamide derivatives
8. History and/or presence of hypersensitivity to Lidocaine
9. History and/or presence of hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components of XIFAXAN
10. History and/or presence of hypersensitivity to acrylate or methacrylate, commonly used components of medical adhesives
11. Any other factor, condition, or disease, including, but not limited to, cardiovascular, respiratory, hematological, renal, hepatic, or gastrointestinal disorders that may, in the opinion of the Investigator, jeopardize the safety of the patient, alter drug absorption and pharmacokinetics or impact the validity of the study results.
12. Subjects with Type 1 Diabetes Mellitus (DM), diabetic ketoacidosis, with or without coma
13. Subjects with Glucose 6-phosphate dehydrogenase (G6PD) deficiency
14. History and/or presence of drug addiction or alcohol abuse within the past 12 months.
15. History of significant psychiatric or neurological illness, including seizure disorders.
16. Any medical or surgical conditions which might significantly interfere with the functions of gastrointestinal tract (e.g., gastric/intestinal bypass surgeries, fistulas, strictures, stenosis, or physiological/mechanical obstruction of the G.I tract, gastric bezoars, irritable bowel disease, crohn's disease, diverticulosis, or chronic narcotic use).
17. History of dysphagia to liquids, food, or pills
18. History of abdominal radiation therapy
19. Pregnant or lactating females
20. Any clinically significant abnormal lab values during screening in the opinion of the investigator.
21. Use of alcohol and/or nicotine containing products 48 hours prior to dosing visits, and throughout PK sampling visits.
22. Use of any medications and/or supplements, prescriptions or over the counter 1 week prior to beginning the study, and throughout the study except for birth control with approved methods of contraception when used consistently and correctly (Implants (i.e. Implanon, Nexplanon), Injectables (i.e. Depo-Provera), Combined, Oral Contraceptives, Intrauterine Devices (IUD's) (i.e. Mirena, ParaGard), and Sexual Abstinence are accepted).
23. Use of aspirin or any blood thinner medications.
24. Use of an implanted or portable electro-mechanical medical device such as a cardiac pacemaker or infusion pump.
25. Volunteers unwilling or unable to take the proposed drugs or undergo G.I intubation
26. Enrollment in a clinical trial in the past 30 days
27. Current enrollment in a clinical trial with another study drug, vaccine or medical device
28. Fasting blood glucose level < 80 mg/dL.
29. Inability or unwillingness to fast for 19 hours.
30. Blood donations in the past 8 weeks except for apheresis.
31. Volunteer shows a positive result of COVID-19 Antigen Rapid test in dosing visits

32. Volunteer is having any of the following symptoms:

    • Fever (over 100.4 oF or 38 oC) or feeling feverish
    • New cough
    • New shortness of breath

33. Volunteer is having two of any of these symptoms:

    • Chills
    • Muscle aches
    • New URI symptom(s) (runny nose, nasal congestion, and/or sore throat)
    • New loss of sense of smell or sense of taste
    • New headache
34. Volunteer has been in close contact in the last 14 days with someone recently diagnosed with COVID-19
35. Volunteer has returned from international travel within the past 10 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: G.I Intubation; 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.

Drug: Glucotrol XL 5Mg Extended-Release Tablet; Participants are randomized to take one tablet of this study drug by mouth.; Drug: Glipizide ER 5 MG 24 HR Extended Release Oral Tablet; Participants are randomized to take one tablet of this study drug by mouth.; Drug: Rifaximin 200Mg Tab; Participants will take one tablet of this study drug by mouth.; Drug: 13C6-Glipizide; Participants will take 1 mg of this study drug dissolved in 40 ml glucose solution by mouth.; Other Names: Stable Isotope Glipizide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Area Under the Plasma Concentration-time Curve to infinite time (AUCinfinity) of Glipizide After a Single Dose of Glipizide with Gastrointestinal Intubation and between Two Modified Release Glipizide formulations	Average Area Under the Plasma Concentration-time Curve to infinite time (AUCinfinity) of Glipizide will be measured at multiple timepoints over a 78 hour period at each of the two study phases	From time 0 to 78 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Gastrointestinal fluid concentration of Glipizide after Oral Administration of a Single Dose Modified Released Formulation of Glipizide	The concentration of Glipizide in gastrointestinal fluid (stomach, duodenum, jejunum and ileum) will be measured at multiple timepoints over a 7 hour period using a 4-port G.I Intubation Catheter	From time 0 to 7 hours
Gastrointestinal pH after Oral Administration of Modified Release Formulation of Glipizide	Gastrointestinal pH will be measured ex-vivo in gastrointestinal fluid samples collected through gastrointestinal intubation catheter over a duration of 7 hours.	From time 0 to 7 hours
Plasma Cmax of Glipizide After a Single Dose of Glipizide with Gastrointestinal Intubation and between Two Modified Release Glipizide formulations	Peak Plasma Concentration of Glipizide (Cmax) will be measured at multiple timepoints over a 78 hour period at the study phase	From time 0 to 78 hours
Plasma Tmax of Glipizide After a Single Dose of Glipizide with Gastrointestinal Intubation and between Two Modified Release Glipizide formulations	The time it takes to reach the maximum concentration of Glipizide in Plasma (Tmax) will be measured at multiple timepoints over a 78 hour period at the study phase	From time 0 to 78 hours
Urine and Feces concentrations of Glipizide After a Single Dose of Glipizide with Gastrointestinal Intubation and between Two Modified Release Glipizide formulations	Recovery of Glipizide in urine and feces will be measured at multiple timepoints over a 78 hour period at the study phase	From time 0 to 78 hours

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Food and Drug Administration (FDA)
• Investigators: Study Director: Cathrin Ring, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2022
• Primary Completion (Actual): March 24, 2026
• Study Completion (Actual): March 29, 2026

Study Registration Dates

• First Submitted: November 17, 2021
• First Submitted That Met QC Criteria: December 1, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): July 20, 2026
• Last Update Submitted That Met QC Criteria: July 16, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Clinical study; Glipizide; Modified release; In vivo dissolution; Local gastrointestinal concentration
• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Sulfones; Sulfonylurea Compounds; Rifaximin; Glipizide
• Other Study ID Numbers: HUM00199603

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes