Trial Outcomes & Findings for Correlation of Mesalamine Pharmacokinetics With Local Availability (NCT NCT01999400)

NCT ID: NCT01999400

Last Updated: 2017-05-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

30 participants

Primary outcome timeframe

0 hours pre-dose and up to 96 hours post-dose

Results posted on

2017-05-15

Participant Flow

Participant milestones

Participant milestones
Measure
Arm 1: Pentasa Then Delzicol Then Apriso Then Lialda
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
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
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
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
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
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.
First Intervention (1 Day)
STARTED
6
6
5
5
4
4
First Intervention (1 Day)
COMPLETED
4
4
3
2
4
3
First Intervention (1 Day)
NOT COMPLETED
2
2
2
3
0
1
Washout (10 Days)
STARTED
1
0
1
0
0
0
Washout (10 Days)
COMPLETED
1
0
1
0
0
0
Washout (10 Days)
NOT COMPLETED
0
0
0
0
0
0
Second Intervention (1 Day)
STARTED
5
4
3
2
3
3
Second Intervention (1 Day)
COMPLETED
5
4
3
2
3
3
Second Intervention (1 Day)
NOT COMPLETED
0
0
0
0
0
0
Third Intervention (1 Day)
STARTED
2
0
1
1
1
1
Third Intervention (1 Day)
COMPLETED
2
0
1
1
1
0
Third Intervention (1 Day)
NOT COMPLETED
0
0
0
0
0
1
Fourth Intervention (1 Day)
STARTED
1
0
1
0
0
0
Fourth Intervention (1 Day)
COMPLETED
1
0
1
0
0
0
Fourth Intervention (1 Day)
NOT COMPLETED
0
0
0
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Correlation of Mesalamine Pharmacokinetics With Local Availability

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Study Participants
n=30 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
Age, Continuous
32.9 years
STANDARD_DEVIATION 9.7 • n=99 Participants
Sex: Female, Male
Female
9 Participants
n=99 Participants
Sex: Female, Male
Male
21 Participants
n=99 Participants
Body Mass Index
26.9 kg per m squared
STANDARD_DEVIATION 5.6 • n=99 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Pentasa
n=10 Participants
Pentasa 500 mg capsule x 2 with 240 mL water, single dose Pentasa 500 mg capsule x 2 with 240 mL water; single dose
Apriso
n=7 Participants
Apriso 375 mg capsule x 3 with 240 mL water, single dose Apriso 375 mg capsule x 3 with 240 mL water; single dose
Lialda
n=9 Participants
Lialda 1200 mg tablet x 1 with 240 mL water, single dose Lialda 1200 mg tablet x 1 with 240 mL water; single dose
Delzicol
n=20 Participants
Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose
The AUC of Mesalamine in Plasma
40.8 nM*h
Standard Deviation 29.5
57.6 nM*h
Standard Deviation 24.1
36.8 nM*h
Standard Deviation 16.0
7.9 nM*h
Standard Deviation 3.7

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Pentasa
n=10 Participants
Pentasa 500 mg capsule x 2 with 240 mL water, single dose Pentasa 500 mg capsule x 2 with 240 mL water; single dose
Apriso
n=7 Participants
Apriso 375 mg capsule x 3 with 240 mL water, single dose Apriso 375 mg capsule x 3 with 240 mL water; single dose
Lialda
n=9 Participants
Lialda 1200 mg tablet x 1 with 240 mL water, single dose Lialda 1200 mg tablet x 1 with 240 mL water; single dose
Delzicol
n=20 Participants
Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose
The AUC of Metabolite (N-acetyl-mesalamine) in Plasma
162 nM*h
Standard Deviation 59.7
189 nM*h
Standard Deviation 92.2
124 nM*h
Standard Deviation 80.5
20.4 nM*h
Standard Deviation 7.7

SECONDARY outcome

Timeframe: 0 hours pre-dose and up to 7 hours post-dose

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Pentasa
n=3 Participants
Pentasa 500 mg capsule x 2 with 240 mL water, single dose Pentasa 500 mg capsule x 2 with 240 mL water; single dose
Apriso
n=3 Participants
Apriso 375 mg capsule x 3 with 240 mL water, single dose Apriso 375 mg capsule x 3 with 240 mL water; single dose
Lialda
n=3 Participants
Lialda 1200 mg tablet x 1 with 240 mL water, single dose Lialda 1200 mg tablet x 1 with 240 mL water; single dose
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
The AUC of Mesalamine in Distal Jejunum
8456 uM*h
Standard Deviation 7444
4923 uM*h
Standard Deviation 8506
2.9 uM*h
Standard Deviation 3.9

SECONDARY outcome

Timeframe: 0 hours pre-dose and up to 7 hours post-dose

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Pentasa
n=3 Participants
Pentasa 500 mg capsule x 2 with 240 mL water, single dose Pentasa 500 mg capsule x 2 with 240 mL water; single dose
Apriso
n=3 Participants
Apriso 375 mg capsule x 3 with 240 mL water, single dose Apriso 375 mg capsule x 3 with 240 mL water; single dose
Lialda
n=3 Participants
Lialda 1200 mg tablet x 1 with 240 mL water, single dose Lialda 1200 mg tablet x 1 with 240 mL water; single dose
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
The AUC of Metabolite (N-acetyl-mesalamine) in Distal Jejunum
5048 uM*h
Standard Deviation 5553
1225 uM*h
Standard Deviation 2024
3.4 uM*h
Standard Deviation 3.4

Adverse Events

Pentasa

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Apriso

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Lialda

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Delzicol

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Pentasa
n=14 participants at risk
Pentasa 500 mg capsule x 2 with 240 mL water, single dose Pentasa 500 mg capsule x 2 with 240 mL water; single dose
Apriso
n=13 participants at risk
Apriso 375 mg capsule x 3 with 240 mL water, single dose Apriso 375 mg capsule x 3 with 240 mL water; single dose
Lialda
n=11 participants at risk
Lialda 1200 mg tablet x 1 with 240 mL water, single dose Lialda 1200 mg tablet x 1 with 240 mL water; single dose
Delzicol
n=20 participants at risk
Delzicol 100 mg mesalamine x 1 with 245 mL water, single dose Delzicol 100 mg mesalamine x 1 with 245 mL water; single dose
Nervous system disorders
vasovagal syncope
0.00%
0/14
0.00%
0/13
9.1%
1/11
0.00%
0/20

Additional Information

Dr. Duxin Sun

University of Michigan

Phone: 734-763-9783

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place