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

NCT ID: NCT02806869

Last Updated: 2017-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2017-07-31

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.

Conditions

Human Gastrointestinal Physiology Data

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Single dose of ibuprofen (800 mg tablet)

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Single dose of ibuprofen (800 mg tablet)

Intervention Type: DRUG

Pulmocare, two 8.0 oz (236.6 mL) cans

Intervention Type: DIETARY_SUPPLEMENT

Interventions

Single dose of ibuprofen (800 mg tablet)

Intervention Type: DRUG

Pulmocare, two 8.0 oz (236.6 mL) cans

Intervention Type: DIETARY_SUPPLEMENT

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Food and Drug Administration (FDA)

FED

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Duxin Sun

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Duxin Sun, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28980204 (View on PubMed)

Other Identifiers

HHSF223201310144C

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

FDA_13-RFQ-1116088

Identifier Type: -

Identifier Source: org_study_id