Clinical trial NCT02806869: Modernization of in vivo-in Vitro Oral Bioperformance Prediction and Assessment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Human Gastrointestinal Physiology Data
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
First posted: 2016-06-21
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Average Duodenal Fluid pH in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen
timeFrame: from time 0 to 7 hours
Secondary outcomes:
measure: Maximum Duodenal Fluid Concentration of Ibuprofen in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen
timeFrame: from time 0 to 7 hours
measure: Average Area Under the Plasma Concentration-time Curve (AUC) in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen
timeFrame: from time 0 to 24 hours
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Duxin Sun, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yu A, Jackson T, Tsume Y, Koenigsknecht M, Wysocki J, Marciani L, Amidon GL, Frances A, Baker JR, Hasler W, Wen B, Pai A, Sun D. Mechanistic Fluid Transport Model to Estimate Gastrointestinal Fluid Volume and Its Dynamic Change Over Time. AAPS J. 2017 Nov;19(6):1682-1690. doi: 10.1208/s12248-017-0145-x. Epub 2017 Oct 4.