Clinical trial NCT01999400
Conditions: Local Drug Concentration in Gastrointestinal Tract
Sponsor: University of Michigan
Start date: 2012-04-01; Completion date: 2017-04-01
Enrollment: 30 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

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.

Arms: arm 1: 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: 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: 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: 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: 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: 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.
Interventions: intervention 1: Pentasa 500 mg capsule x 2 with 240 mL water; single dose intervention 2: Apriso 375 mg capsule x 3 with 240 mL water; single dose intervention 3: Lialda 1200 mg tablet x 1 with 240 mL water; single dose intervention 4: Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents: