Correlation of Mesalamine Pharmacokinetics With Local Availability

Not Applicable

Completed

• Conditions: Local Drug Concentration in Gastrointestinal Tract
• Interventions: Drug: Pentasa 500 mg capsule x 2 with 240 mL water; single dose; Drug: Apriso 375 mg capsule x 3 with 240 mL water; single dose; Drug: Lialda 1200 mg tablet x 1 with 240 mL water; single dose; Drug: Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose

• Registration Number: NCT01999400
• Lead Sponsor: University of Michigan

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.

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2013-11-25
• Study First Submitted QC: 2013-11-25
• Study First Posted: 2013-12-03
• Primary Completion: 2015-09
• Results First Submitted: 2016-11-07
• Study Completion: 2017-04
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-02
• Last Update Submitted: 2017-05-02
• Results First Posted: 2017-05-15
• Last Update Posted: 2017-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm 2: Pentasa then Delzicol then Lialda then Apriso	Lialda 1200 mg tablet x 1 with 240 mL water; single dose	1. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Apriso 375 mg capsule x 3 with 240 mL water, single dose.
Arm 4: Apriso then Delzicol then Lialda then Pentasa	Lialda 1200 mg tablet x 1 with 240 mL water; single dose	1. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Pentasa 500 mg capsule x 2 with 240 mL water, single dose.
Arm 1: Pentasa then Delzicol then Apriso then Lialda	Pentasa 500 mg capsule x 2 with 240 mL water; single dose	1. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Lialda 1200 mg tablet x 1 with 240 mL water, single dose.
Arm 1: Pentasa then Delzicol then Apriso then Lialda	Lialda 1200 mg tablet x 1 with 240 mL water; single dose	1. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Lialda 1200 mg tablet x 1 with 240 mL water, single dose.
Arm 2: Pentasa then Delzicol then Lialda then Apriso	Pentasa 500 mg capsule x 2 with 240 mL water; single dose	1. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Apriso 375 mg capsule x 3 with 240 mL water, single dose.
Arm 3: Apriso then Delzicol then Pentasa then Lialda	Lialda 1200 mg tablet x 1 with 240 mL water; single dose	1. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Lialda 1200 mg tablet x 1 with 240 mL water, single dose.
Arm 5: Lialda then Delzicol then Pentasa then Apriso	Lialda 1200 mg tablet x 1 with 240 mL water; single dose	1. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Apriso 375 mg capsule x 3 with 240 mL water, single dose.
Arm 6: Lialda then Delzicol then Apriso then Pentasa	Lialda 1200 mg tablet x 1 with 240 mL water; single dose	1. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Pentasa 500 mg capsule x 2 with 240 mL water, single dose.
Arm 4: Apriso then Delzicol then Lialda then Pentasa	Pentasa 500 mg capsule x 2 with 240 mL water; single dose	1. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Pentasa 500 mg capsule x 2 with 240 mL water, single dose.
Arm 5: Lialda then Delzicol then Pentasa then Apriso	Pentasa 500 mg capsule x 2 with 240 mL water; single dose	1. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Apriso 375 mg capsule x 3 with 240 mL water, single dose.
Arm 6: Lialda then Delzicol then Apriso then Pentasa	Pentasa 500 mg capsule x 2 with 240 mL water; single dose	1. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Pentasa 500 mg capsule x 2 with 240 mL water, single dose.
Arm 3: Apriso then Delzicol then Pentasa then Lialda	Pentasa 500 mg capsule x 2 with 240 mL water; single dose	1. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Lialda 1200 mg tablet x 1 with 240 mL water, single dose.
Arm 1: Pentasa then Delzicol then Apriso then Lialda	Apriso 375 mg capsule x 3 with 240 mL water; single dose	1. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Lialda 1200 mg tablet x 1 with 240 mL water, single dose.
Arm 1: Pentasa then Delzicol then Apriso then Lialda	Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose	1. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Lialda 1200 mg tablet x 1 with 240 mL water, single dose.
Arm 2: Pentasa then Delzicol then Lialda then Apriso	Apriso 375 mg capsule x 3 with 240 mL water; single dose	1. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Apriso 375 mg capsule x 3 with 240 mL water, single dose.
Arm 2: Pentasa then Delzicol then Lialda then Apriso	Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose	1. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Apriso 375 mg capsule x 3 with 240 mL water, single dose.
Arm 3: Apriso then Delzicol then Pentasa then Lialda	Apriso 375 mg capsule x 3 with 240 mL water; single dose	1. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Lialda 1200 mg tablet x 1 with 240 mL water, single dose.
Arm 3: Apriso then Delzicol then Pentasa then Lialda	Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose	1. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Lialda 1200 mg tablet x 1 with 240 mL water, single dose.
Arm 4: Apriso then Delzicol then Lialda then Pentasa	Apriso 375 mg capsule x 3 with 240 mL water; single dose	1. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Pentasa 500 mg capsule x 2 with 240 mL water, single dose.
Arm 4: Apriso then Delzicol then Lialda then Pentasa	Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose	1. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Pentasa 500 mg capsule x 2 with 240 mL water, single dose.
Arm 5: Lialda then Delzicol then Pentasa then Apriso	Apriso 375 mg capsule x 3 with 240 mL water; single dose	1. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Apriso 375 mg capsule x 3 with 240 mL water, single dose.
Arm 5: Lialda then Delzicol then Pentasa then Apriso	Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose	1. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Pentasa 500 mg capsule x 2 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Apriso 375 mg capsule x 3 with 240 mL water, single dose.
Arm 6: Lialda then Delzicol then Apriso then Pentasa	Apriso 375 mg capsule x 3 with 240 mL water; single dose	1. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Pentasa 500 mg capsule x 2 with 240 mL water, single dose.
Arm 6: Lialda then Delzicol then Apriso then Pentasa	Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose	1. Lialda 1200 mg tablet x 1 with 240 mL water, single dose. 2. Washout period of 10 days. 3. Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose. 4. Washout period of 10 days. 5. Apriso 375 mg capsule x 3 with 240 mL water, single dose. 6. Washout period of 10 days. 7. Pentasa 500 mg capsule x 2 with 240 mL water, single dose.

Primary Outcome Measures

Name	Time	Method
The AUC of Mesalamine in Plasma	0 hours pre-dose and up to 96 hours post-dose	The AUC is the area under the concentration-time curve from time 0 to last time point. The data are organized by the different drug formulations of mesalamine, which include Pentasa (0 to 72 hours), Apriso (0 to 72 hours), Lialda (0 to 96 hours), and Delzicol (0 to 24 hours). The AUC is measured in units of nanomoles of mesalamine per liter of plasma (nM) multiplied by time in hours (nM\*h). The AUC results are reported over the time-period because this provides a more meaningful comparison of potential differences in the bioequivalence of formulations.
The AUC of Metabolite (N-acetyl-mesalamine) in Plasma	0 hours pre-dose and up to 96 hours post-dose	The AUC is the area under the concentration-time curve from time 0 to last time point. The data are organized by the different drug formulations of mesalamine, which include Pentasa (0 to 72 hours), Apriso (0 to 72 hours), Lialda (0 to 96 hours), and Delzicol (0 to 24 hours). The AUC is measured in units of nanomoles of N-acetyl-mesalamine per liter of plasma (nM) multiplied by time in hours (nM\*h). The AUC results are reported over the time-period because this provides a more meaningful comparison of potential differences in the bioequivalence of formulations.

Secondary Outcome Measures

Name	Time	Method
The AUC of Mesalamine in Distal Jejunum	0 hours pre-dose and up to 7 hours post-dose	The AUC is the area under the concentration-time curve from time 0 to 7 hours. The data are organized by the different drug formulations of mesalamine, which include Pentasa, Apriso, and Lialda. The AUC is measured in units of micromoles of mesalamine per liter of plasma (µM) multiplied by time in hours (µM\*h).The AUC results are reported over the time-period because this provides a more meaningful comparison of potential differences in the bioequivalence of formulations. The solution formulation (Delzicol) was not administered in this portion of the study. Therefore no results pertaining to the solution formulation are included in this outcome measure.
The AUC of Metabolite (N-acetyl-mesalamine) in Distal Jejunum	0 hours pre-dose and up to 7 hours post-dose	The AUC is the area under the concentration-time curve from time 0 to 7 hours. The data are organized by the different drug formulations of mesalamine, which include Pentasa, Apriso, and Lialda. The AUC is measured in units of micromoles of mesalamine per liter of plasma (µM) multiplied by time in hours (µM\*h).The AUC results are reported over the time-period because this provides a more meaningful comparison of potential differences in the bioequivalence of formulations. The solution formulation (Delzicol) was not administered in this portion of the study. Therefore no results pertaining to the solution formulation are included in this outcome measure.

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States