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| ID | Type | Description | Link |
|---|---|---|---|
| HHSF223201300460A | Other Grant/Funding Number | U.S. Food and Drug Administration | |
| HHSF223201000082C | Other Grant/Funding Number | U.S. Food and Drug Administration |
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| Name | Class |
|---|---|
| Food and Drug Administration (FDA) | FED |
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Pentasa then Delzicol then Apriso then Lialda | Experimental |
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| Arm 2: Pentasa then Delzicol then Lialda then Apriso | Experimental |
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| Arm 3: Apriso then Delzicol then Pentasa then Lialda | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pentasa 500 mg capsule x 2 with 240 mL water; single dose | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| The AUC of Mesalamine in Plasma | 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. | 0 hours pre-dose and up to 96 hours post-dose |
| The AUC of Metabolite (N-acetyl-mesalamine) in Plasma | 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. | 0 hours pre-dose and up to 96 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| The AUC of Mesalamine in Distal Jejunum | 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. |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Duxin Sun, Ph.D. | University of Michigan, College of Pharmacy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18446510 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: Pentasa Then Delzicol Then Apriso Then Lialda |
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| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention (1 Day) |
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| Arm 4: Apriso then Delzicol then Lialda then Pentasa | Experimental |
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| Arm 5: Lialda then Delzicol then Pentasa then Apriso | Experimental |
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| Arm 6: Lialda then Delzicol then Apriso then Pentasa | Experimental |
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| Apriso 375 mg capsule x 3 with 240 mL water; single dose | Drug |
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| Lialda 1200 mg tablet x 1 with 240 mL water; single dose | Drug |
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| Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose | Drug |
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| 0 hours pre-dose and up to 7 hours post-dose |
| The AUC of Metabolite (N-acetyl-mesalamine) in Distal Jejunum | 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. | 0 hours pre-dose and up to 7 hours post-dose |
| FG001 | Arm 2: Pentasa Then Delzicol Then Lialda Then Apriso |
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| FG002 | Arm 3: Apriso Then Delzicol Then Pentasa Then Lialda |
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| FG003 | Arm 4: Apriso Then Delzicol Then Lialda Then Pentasa |
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| FG004 | Arm 5: Lialda Then Delzicol Then Pentasa Then Apriso |
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| FG005 | Arm 6: Lialda Then Delzicol Then Apriso Then Pentasa |
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| COMPLETED |
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| NOT COMPLETED |
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| Washout (10 Days) |
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| Second Intervention (1 Day) |
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| Washout (10 Days) |
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| Third Intervention (1 Day) |
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| Washout (10 Days) |
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| Fourth Intervention (1 Day) |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants who were randomized to one of the six arms of this study: Arm 1: Pentasa then Delzicol then Apriso then Lialda Arm 2: Pentasa then Delzicol then Lialda then Apriso Arm 3: Apriso then Delzicol then Pentasa then Lialda Arm 4: Apriso then Delzicol then Lialda then Pentasa Arm 5: Lialda then Delzicol then Pentasa then Apriso Arm 6: Lialda then Delzicol then Apriso then Pentasa |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Body Mass Index | Mean | Standard Deviation | kg per m squared |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The AUC of Mesalamine in Plasma | 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. | Posted | Mean | Standard Deviation | nM*h | 0 hours pre-dose and up to 96 hours post-dose |
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| Primary | The AUC of Metabolite (N-acetyl-mesalamine) in Plasma | 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. | Posted | Mean | Standard Deviation | nM*h | 0 hours pre-dose and up to 96 hours post-dose |
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| Secondary | The AUC of Mesalamine in Distal Jejunum | 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 number of subjects that were administered Pentasa, Apriso, Lialda were 10, 7, and 9, respectively. However, we were only able to collect gastrointestinal fluid from the distal jejunum for only 3 subjects in each of these arms due to the placement of the gastrointestinal tube. | Posted | Mean | Standard Deviation | uM*h | 0 hours pre-dose and up to 7 hours post-dose |
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| Secondary | The AUC of Metabolite (N-acetyl-mesalamine) in Distal Jejunum | 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 number of subjects that were administered Pentasa, Apriso, Lialda were 10, 7, and 9, respectively. However, we were only able to collect gastrointestinal fluid from the distal jejunum for only 3 subjects in each of these arms due to the placement of the gastrointestinal tube. | Posted | Mean | Standard Deviation | uM*h | 0 hours pre-dose and up to 7 hours post-dose |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pentasa | Pentasa 500 mg capsule x 2 with 240 mL water, single dose Pentasa 500 mg capsule x 2 with 240 mL water; single dose | 0 | 14 | 0 | 14 | ||
| EG001 | Apriso | Apriso 375 mg capsule x 3 with 240 mL water, single dose Apriso 375 mg capsule x 3 with 240 mL water; single dose | 0 | 13 | 0 | 13 | ||
| EG002 | Lialda | Lialda 1200 mg tablet x 1 with 240 mL water, single dose Lialda 1200 mg tablet x 1 with 240 mL water; single dose | 0 | 11 | 1 | 11 | ||
| EG003 | Delzicol | Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose | 0 | 20 | 0 | 20 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| vasovagal syncope | Nervous system disorders | Non-systematic Assessment |
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Evaluation of healthy volunteers that may not reflect patients with inflammatory bowel disease.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Duxin Sun | University of Michigan | 734-763-9783 | pharmacy.research@umich.edu |
| ID | Term |
|---|---|
| D019804 | Mesalamine |
| D014867 | Water |
| ID | Term |
|---|---|
| D062368 | meta-Aminobenzoates |
| D062365 | Aminobenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D000636 | Aminosalicylic Acids |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D006880 | Hydroxy Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010636 | Phenols |
| D006878 | Hydroxides |
| D000468 | Alkalies |
| D007287 | Inorganic Chemicals |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |
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| Delzicol |
Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose |
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| Lialda |
Lialda 1200 mg tablet x 1 with 240 mL water, single dose Lialda 1200 mg tablet x 1 with 240 mL water; single dose |
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| OG002 |
| Lialda |
Lialda 1200 mg tablet x 1 with 240 mL water, single dose Lialda 1200 mg tablet x 1 with 240 mL water; single dose |
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