Modernization of in vivo-in Vitro Oral Bioperformance Prediction and Assessment

University of Michigan

Status: Completed

Conditions: Human Gastrointestinal Physiology Data

Treatments: Dietary Supplement: Pulmocare, two 8.0 oz (236.6 mL) cans; Drug: Single dose of ibuprofen (800 mg tablet)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT02806869

FDA_13-RFQ-1116088

HHSF223201310144C (Other Grant/Funding Number)

Details and patient eligibility

About

In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study was to evaluate the in vivo drug dissolution and systemic absorption of the BCS Class IIa drug ibuprofen under fed and fasted conditions by direct sampling of stomach and small intestinal luminal content. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution.

Full description

This is an in vivo study designed to acquire human gastrointestinal (GI) physiology data from healthy subjects under fasting and fed conditions which are necessary for mechanistic absorption model development. Each subject will be asked to complete two GI tube insertion procedures. Subjects will complete this study twice under the same conditions of the GI tract, either fasting state or fed state, in order to provide intra-subject variability. A minimum of 7 days will separate each GI tube insertion procedure. The objectives of this study are, as follows: Objective #1: To acquire human GI physiology data including GI motility, pH of GI fluids, and GI fluid volume under fasting and fed conditions; Objective #2: To measure drug concentration and calculate drug dissolution in the GI tract in vivo under fasting and fed conditions; Objective #3: To monitor plasma drug concentration and evaluate pharmacokinetics of administered drug during GI tube insertion studies under fasting and fed conditions. 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.

Enrollment: 48 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Adults age 18 to 55.
2. Male or female voluntarily able to give informed consent.

Exclusion criteria

1. Adults unable to consent for themselves or mentally incapacitated.
2. Prisoners.
3. Significant clinical illness within 3 weeks prior to Screening.
4. Use of concomitant medications within 2 weeks prior to receiving study drug, including but not limited to prescription drugs, herbal and dietary supplements, over the counter medications, and vitamins. Birth control is permitted.
5. Received an investigational drug within 60 days prior to receiving the study drug.
6. History of gastrointestinal surgery.
7. Surgery within the past 3 months.
8. History of allergy to ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs).
9. History of severe allergic diseases including drug allergies, with the exception of seasonal allergies.
10. Any other factor, condition, or disease, including, but not limited to, cardiovascular, renal, hepatic, or gastrointestinal disorders that may, in the opinion of the Investigator, jeopardize the safety of the patient or impact the validity of the study results.
11. History of drug addiction or alcohol abuse within the past 12 months.
12. Pregnant or lactating females.
13. Any clinically significant abnormal lab values during Screening.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 2 patient groups

Arm #1 - Fasting State, 2 study visits

Experimental group

Description:

1. Single dose of ibuprofen (800 mg tablet) administered with 250 mL of water containing phenol red 2. Washout period of at least 7 days 3. Single dose of ibuprofen (800 mg tablet) administered with 250 mL of water containing phenol red

Treatment:

Drug: Single dose of ibuprofen (800 mg tablet)

Arm #2 - Fed State, 2 study visits

Experimental group

Description:

1. Pulmocare, two 8.0 oz (236.6 mL) cans, followed by single dose of ibuprofen (800 mg tablet) administered with 250 mL of water containing phenol red 2. Washout period of at least 7 days 3. Pulmocare, two 8.0 oz (236.6 mL) cans, followed by single dose of ibuprofen (800 mg tablet) administered with 250 mL of water containing phenol red

Treatment:

Dietary Supplement: Pulmocare, two 8.0 oz (236.6 mL) cans

Drug: Single dose of ibuprofen (800 mg tablet)