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

NCT02806869 | Completed Results

• 2 other identifiers: FDA_13-RFQ-1116088HHSF223201310144C
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Gastrointestinal Physiology Data

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Maximum Duodenal Fluid Concentration of Ibuprofen in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen

  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

  from time 0 to 24 hours

Study Arms (2)

Arm #1 - Fasting State, 2 study visits

EXPERIMENTAL

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

Drug: Single dose of ibuprofen (800 mg tablet)

Arm #2 - Fed State, 2 study visits

EXPERIMENTAL

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

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

Interventions

Single dose of ibuprofen (800 mg tablet) DRUG

Arm #1 - Fasting State, 2 study visits; Arm #2 - Fed State, 2 study visits

Pulmocare, two 8.0 oz (236.6 mL) cans DIETARY_SUPPLEMENT

Arm #2 - Fed State, 2 study visits

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan: lead
• Food and Drug Administration (FDA): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• 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.

  PMID: 28980204 DERIVED

MeSH Terms

Interventions

Ibuprofen; Tablets

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

The variability associated with concentration-time profile in the gastrointestinal tract could not be associated with participant specific factors given the small study sample size.

Results Point of Contact

• Title: Dr. Duxin Sun
• Organization: University of Michigan

duxins@med.umich.edu

734-615-8740

Study Officials

• Duxin Sun, Ph.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: June 21, 2016
• Study Start: January 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: July 1, 2017
• Last Updated: December 8, 2017
• Results First Posted: December 8, 2017

Record last verified: 2017-11

Locations

US (1)