Human Gastrointestinal Physiology Data
Conditions
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.
Interventions
DRUGSingle dose of ibuprofen (800 mg tablet)
DIETARY_SUPPLEMENTPulmocare, two 8.0 oz (236.6 mL) cans
Sponsors
Food and Drug Administration (FDA)
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Duodenal Fluid pH in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | from time 0 to 7 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Duodenal Fluid Concentration of Ibuprofen in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | from time 0 to 7 hours | 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. |
| Average Area Under the Plasma Concentration-time Curve (AUC) in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | from time 0 to 24 hours | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm #1 - Fasting State, 2 Study Visits 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 | 13 |
| Arm #2 - Fed State, 2 Study Visits 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 | 12 |
| Total | 25 |
Baseline characteristics
| Characteristic | Arm #1 - Fasting State, 2 Study Visits | Arm #2 - Fed State, 2 Study Visits | Total |
|---|---|---|---|
| Age, Continuous | 29.3 years STANDARD_DEVIATION 8.9 | 31.6 years STANDARD_DEVIATION 8.8 | 30.4 years STANDARD_DEVIATION 8.9 |
| Body Mass Index | 25.6 kg/m^2 STANDARD_DEVIATION 4.65 | 26.2 kg/m^2 STANDARD_DEVIATION 4.61 | 25.9 kg/m^2 STANDARD_DEVIATION 4.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 11 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 1 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
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.
Time frame: from time 0 to 7 hours
Population: Overall Number of Participants Analyzed equals the number of participants who completed the First intervention plus the number of participants who completed the Second Intervention. For Arm #1: Overall Number of Participants Analyzed=13+7=20. For Arm #2: Overall Number of Participants Analyzed=12+5=17.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm #1 - Fasting State, 2 Study Visits | Average Duodenal Fluid pH in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | 5.12 pH | Standard Deviation 1.64 |
| Arm #2 - Fed State, 2 Study Visits | Average Duodenal Fluid pH in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | 5.36 pH | Standard Deviation 1.4 |
Secondary
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.
Time frame: from time 0 to 24 hours
Population: Overall Number of Participants Analyzed equals the number of participants who completed the First intervention plus the number of participants who completed the Second Intervention. For Arm #1: Overall Number of Participants Analyzed=13+7=20. For Arm #2: Overall Number of Participants Analyzed=12+5=17.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm #1 - Fasting State, 2 Study Visits | Average Area Under the Plasma Concentration-time Curve (AUC) in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | 242 h*mg/L | Standard Deviation 88.9 |
| Arm #2 - Fed State, 2 Study Visits | Average Area Under the Plasma Concentration-time Curve (AUC) in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | 229 h*mg/L | Standard Deviation 76.9 |
Secondary
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.
Time frame: from time 0 to 7 hours
Population: Overall Number of Participants Analyzed equals the number of participants who completed the First intervention plus the number of participants who completed the Second Intervention. For Arm #1: Overall Number of Participants Analyzed=13+7=20. For Arm #2: Overall Number of Participants Analyzed=12+5=17.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm #1 - Fasting State, 2 Study Visits | Maximum Duodenal Fluid Concentration of Ibuprofen in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | 217 mg/L | Standard Deviation 230 |
| Arm #2 - Fed State, 2 Study Visits | Maximum Duodenal Fluid Concentration of Ibuprofen in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen | 155 mg/L | Standard Deviation 172 |