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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed 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.

Official Title
-----------------
Modernization of in vivo-in Vitro Oral Bioperformance Prediction and Assessment: A Research Study to Evaluate the Performance of an Ibuprofen Oral Dosage Form in the Gastrointestinal Tract of Healthy Adult Volunteers

Conditions
-----------------
Human Gastrointestinal Physiology Data

Intervention / Treatment
-----------------
* Drug: Single dose of ibuprofen (800 mg tablet)
* Dietary Supplement: Pulmocare, two 8.0 oz (236.6 mL) cans


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults age 18 to 55. Male or female voluntarily able to give informed consent. Exclusion Criteria: Adults unable to consent for themselves or mentally incapacitated. Prisoners. Significant clinical illness within 3 weeks prior to Screening. 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. Received an investigational drug within 60 days prior to receiving the study drug. History of gastrointestinal surgery. Surgery within the past 3 months. History of allergy to ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs). History of severe allergic diseases including drug allergies, with the exception of seasonal allergies. 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. History of drug addiction or alcohol abuse within the past 12 months. Pregnant or lactating females. Any clinically significant abnormal lab values during Screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a parallel study design that allocated subjects into a fasted or fed group. Subject were asked to complete the same study procedures on two occasions. Subjects assigned to the fasted or fed group were not crossed-over from one group to the other.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm #1 - Fasting State, 2 study visits<br>Single dose of ibuprofen (800 mg tablet) administered with 250 mL of water containing phenol red Washout period of at least 7 days Single dose of ibuprofen (800 mg tablet) administered with 250 mL of water containing phenol red | Drug: Single dose of ibuprofen (800 mg tablet)<br> <br> |
| Experimental: Arm #2 - Fed State, 2 study visits<br>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 Washout period of at least 7 days 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 | Drug: Single dose of ibuprofen (800 mg tablet)<br> <br> Dietary Supplement: Pulmocare, two 8.0 oz (236.6 mL) cans<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Duodenal Fluid pH in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | The pH of duodenal fluid was measured at multiple timepoints over a 7 hour period. The reported value represents the mean and standard deviation of duodenal fluid pH. | from time 0 to 7 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Duodenal Fluid Concentration of Ibuprofen in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | The concentration of duodenal fluid was measured at multiple timepoints over a 7 hour period. The reported value represents the mean and standard deviation maximum concentration measured in duodenal fluid. | from time 0 to 7 hours | 
| Average Area Under the Plasma Concentration-time Curve (AUC) in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | The plasma concentration of ibuprofen was measured at multiple timepoints over a 24 hour period. The reported value represents the mean and standard deviation of AUC over this time frame. | from time 0 to 24 hours |