Clinical trial NCT01999400: Correlation of Mesalamine Pharmacokinetics With Local Availability
Official title: Correlation of Mesalamine Pharmacokinetics With Local Availability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Local Drug Concentration in Gastrointestinal Tract
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
First posted: 2013-12-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study is designed to provide data to the FDA correlating pharmacokinetics with local availability of medications within the gastrointestinal tract. This study will support the establishment of scientifically based standards for evaluating drugs which act locally within the gastrointestinal tract. Specific objectives of this study are to: (1) quantify how the plasma concentrations of mesalamine, an agent used to treat inflammatory bowel disease, are correlated with the concentrations in gastrointestinal fluids; and (2) improve the physiologically based models for drug absorption from the intestine. Information from this study in concert with in vitro dissolution data will be used to evaluate in vivo-in vitro correlation (IVIVC) for concentrations in plasma and intestinal lumen and dissolution of mesalamine products.

Detailed description: This study evaluated the pharmacokinetics of mesalamine and its major metabolite of mesalamine known as N-acetyl-mesalamine in plasma. Mesalamine is available in different formulations that control the rate at which they are released in the gastrointestinal tract. Three formulations of mesalamine, Pentasa, Apriso, and Lialda, were studied in the crossover phase, while an oral solution formulation of mesalamine was studied in the single-arm phase. Each subject participated in a crossover phase study with one of the three formulations assigned at random using block randomization. Then the subject entered the single-arm phase study. After participation in one crossover phase study and one single-arm phase study, the subject could opt to participate in crossover phase studies using the other formulations also chosen at random until all three formulations were studied. The single-arm phase study was not repeated on returning subjects who participated in more than one crossover phase study.

Eligibility criteria: Inclusion Criteria

1. Adults age 18 to 55.
2. Male or female voluntarily able to give informed consent.
3. Body mass index (BMI) 18.5 to 35.

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. Oral contraception is permitted.
5. History of gastrointestinal surgery.
6. History of allergy to non-steroidal anti-inflammatory drugs (NSAIDs) or to any of the ingredients of Asacol, Pentasa, Apriso, or Lialda.
7. History of severe allergic diseases including drug allergies, with the exception of seasonal allergies.
8. 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.
9. History of drug addiction or alcohol abuse within the past 12 months.
10. Pregnant or lactating females.
11. Surgery within the past 3 months.
12. Received an investigational drug within 60 days prior to receiving the study drug.
13. Any clinically significant abnormal lab values during Screening.

Primary outcomes:
measure: The AUC of Mesalamine in Plasma
timeFrame: 0 hours pre-dose and up to 96 hours post-dose
measure: The AUC of Metabolite (N-acetyl-mesalamine) in Plasma
timeFrame: 0 hours pre-dose and up to 96 hours post-dose
Secondary outcomes:
measure: The AUC of Mesalamine in Distal Jejunum
timeFrame: 0 hours pre-dose and up to 7 hours post-dose
measure: The AUC of Metabolite (N-acetyl-mesalamine) in Distal Jejunum
timeFrame: 0 hours pre-dose and up to 7 hours post-dose
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan, College of Pharmacy
name: Duxin Sun, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lionberger RA. FDA critical path initiatives: opportunities for generic drug development. AAPS J. 2008;10(1):103-9. doi: 10.1208/s12248-008-9010-2. Epub 2008 Feb 20.