Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to evaluate the relative bioavailability of the test formulation of mesalamine suspension rectal enema with the already marketed reference formulation Rowasa® in healthy, adult subjects.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
DRUGRowasa® 4 gm/60 mL Rectal Enema
1 x 4 gm/60 mL, single-dose
DRUGMesalamine 4 gm/60 mL Rectal Enema
1 x 4 gm/60 mL, single-dose
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Males and females, 18 years or older, with a body mass index (BMI) of 30 or less. * Good health as determined by lack of clinically significant abnormalities in health assessments performed at screening. * Signed informed consent form, which meets all criteria of current FDA regulations. * If female and of child bearing potential prepared to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g. condom, IUD, hormonal contraceptives).
Exclusion criteria
* If female pregnant, lactating, or likely to become pregnant during the study. * History of allergy or sensitivity to mesalamine or other salicylic drugs (e.g. aspirin, sulfasalazine) or history of any drug hypersensitivity or intolerance which, in the opinion of the Investigator, would compromise the safety of the subject or the study. * Colitis, hemorrhoids, anal fissures, or other disease of the anus, rectum or colon. * Significant history or current evidence of chronic infections disease, system disorder or organ disorder. * History of psychiatric disorders occuring within the last two years that required hospitalization or medication. * Presence of a medical condition requiring regular treatment with prescription drugs (other than contraceptives). * Use of pharmacologic agents known to significantly induce or inhibit drug-metabolizing enzymes within 30 days prior to dosing. * Receipt of any drug as part of a research study within 30 days prior to dosing. * Drug or alcohol addiction requiring treatment in the past 12 months. * Donation or significant loss of whole blood (480 mL or more) within 30 days or plasma within 14 days prior to dosing. * Positive test for HIV, Hepatitis B surface antigen, or Hepatitis C antibody. * Positive test results for drugs of abuse at screening. * Positive serum pregnancy test at screening. * Unable or unwilling to tolerate multiple venipunctures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 48 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 48 hour period | Bioequivalence based on AUC0-inf |
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | Blood samples collected over 48 hour period | Bioequivalence based on AUC0-t |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 48 hour period | Cmax results for N-Acetylmesalamine metabolite |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 48 hour period | AUC0-inf results for N-Acetylmesalamine metabolite |
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | Blood samples collected over 48 hour period | AUC0-t results for N-Acetylmesalamine metabolite |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mesalamine (Test) First Mesalamine 4gm/60mL Rectal Enema (test) dosed in first period followed by Rowasa® 4gm/60mL Rectal Enema (reference) dosed in second period | 37 |
| Rowasa® (Reference) First Rowasa® 4gm/60mL Rectal Enema (reference) dosed in first period followed by Mesalamine 4gm/60mL Rectal Enema (test) dosed in second period | 35 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Protocol Violation | 1 | 1 |
| Washout | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Rowasa® (Reference) First | Total | Mesalamine (Test) First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 72 Participants | 37 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Biracial | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 16 Participants | 33 Participants | 17 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants | 35 Participants | 18 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 35 participants | 72 participants | 37 participants |
| Sex: Female, Male Female | 12 Participants | 26 Participants | 14 Participants |
| Sex: Female, Male Male | 23 Participants | 46 Participants | 23 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 48 hour period
Population: AUC0-inf was not able to be estimated for all completing subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mesalamine | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 24458.932 ng*h/mL | Standard Deviation 16649.166 |
| Rowasa® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 26862.895 ng*h/mL | Standard Deviation 21419.555 |
90% CI: [82.8, 114]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mesalamine | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 21543.597 ng*h/mL | Standard Deviation 15674.4 |
| Rowasa® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 22911.830 ng*h/mL | Standard Deviation 15380.728 |
90% CI: [83, 107]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mesalamine | Cmax - Maximum Observed Concentration | 1451.739 ng/mL | Standard Deviation 718.488 |
| Rowasa® | Cmax - Maximum Observed Concentration | 1500.290 ng/mL | Standard Deviation 778.674 |
90% CI: [88.6, 107]
Secondary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
AUC0-inf results for N-Acetylmesalamine metabolite
Time frame: Blood samples collected over 48 hour period
Population: AUC0-inf was not able to be estimated for all completing subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mesalamine | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 46564.373 ng*h/mL | Standard Deviation 29109.234 |
| Rowasa® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 49692.278 ng*h/mL | Standard Deviation 32182.649 |
90% CI: [86.7, 110]
Secondary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
AUC0-t results for N-Acetylmesalamine metabolite
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mesalamine | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 40873.915 ng*h/mL | Standard Deviation 25272.348 |
| Rowasa® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 42644.677 ng*h/mL | Standard Deviation 24335.847 |
90% CI: [86.1, 106]
Secondary
Cmax - Maximum Observed Concentration
Cmax results for N-Acetylmesalamine metabolite
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mesalamine | Cmax - Maximum Observed Concentration | 2274.652 ng/mL | Standard Deviation 934.469 |
| Rowasa® | Cmax - Maximum Observed Concentration | 2284.884 ng/mL | Standard Deviation 857.98 |
90% CI: [91.5, 106]