Overactive Bladder (OAB) With Symptoms of Frequency, Urgency, and Urgency
Conditions
Keywords
BIOAVAILABILITY, FOOD EFFECT
Brief summary
This Is A Study Of Bioavailability And Food Effect For Fesoterodine.
Detailed description
To estimate the bioavailability of three different 4 mg fesoterodine ER beads-incapsule formulations compared to 4 mg fesoterodine marketed ER tablets under fasting and fed conditions.
Interventions
DRUGfesoterodine
single dose of beads in capsule
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects between the ages of 18 and 55 years
Exclusion criteria
* Evidence or history of clinically significant disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT]) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hours (hrs) post dose | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Fesoterodine Metabolite (5-HMT) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hrs post dose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of 5-HMT. |
| Maximum Observed Plasma Concentration (Cmax) for Fesoterodine Metabolite (5-HMT) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hrs post dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for Fesoterodine Metabolite (5-HMT) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hrs post dose | — |
| Plasma Decay Half Life (t1/2) for Fesoterodine Metabolite (5-HMT) | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hrs post dose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive fesoterodine 4 mg IR-BIC fasted first, 10% ER-BIC fasted first, 15% ER-BIC fasted first, 20% ER-BIC fasted first and ER tablets fasted first. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 39.5 years STANDARD_DEVIATION 10.8 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 20 | 4 / 20 | 6 / 20 | 0 / 20 | 4 / 20 | 6 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT])
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hours (hrs) post dose
Population: Pharmacokinetic (PK) parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here, the N (number of participants analyzed) is signifying the number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine 4 mg IR-BIC Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT]) | 30.48 ng*hr/mL | Standard Deviation 11.77 |
| Fesoterodine 4 mg 10% ER-BIC Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT]) | 28.24 ng*hr/mL | Standard Deviation 10.35 |
| Fesoterodine 4 mg 15% ER-BIC Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT]) | 19.64 ng*hr/mL | Standard Deviation 7.58 |
| Fesoterodine 4 mg 20% ER-BIC Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT]) | NA ng*hr/mL | — |
| Fesoterodine 4 mg ER Tablet Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT]) | 27.40 ng*hr/mL | Standard Deviation 10.06 |
| Fesoterodine 4 mg 10% ER-BIC Fed | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT]) | 32.07 ng*hr/mL | Standard Deviation 13.24 |
Comparison: Natural log transformed AUC (0 - ∞) of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg IR-BIC Fasted was test.90% CI: [102.69, 120.47]
Comparison: Natural log transformed AUC (0 - ∞) of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg 10% ER-BIC Fasted was test.90% CI: [95.16, 111.64]
Comparison: Natural log transformed AUC (0 - ∞) of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg 15% ER-BIC Fasted was test.90% CI: [64.52, 76.74]
Comparison: Natural log transformed AUC (0 - ∞) of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg 10% ER-BIC Fasted was reference and Fesoterodine 4 mg 10% ER-BIC Fed was test.90% CI: [105.91, 121.74]
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Fesoterodine Metabolite (5-HMT)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of 5-HMT.
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hrs post dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine 4 mg IR-BIC Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Fesoterodine Metabolite (5-HMT) | 30.23 ng*hr/mL | Standard Deviation 11.79 |
| Fesoterodine 4 mg 10% ER-BIC Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Fesoterodine Metabolite (5-HMT) | 27.79 ng*hr/mL | Standard Deviation 10.21 |
| Fesoterodine 4 mg 15% ER-BIC Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Fesoterodine Metabolite (5-HMT) | 17.92 ng*hr/mL | Standard Deviation 6.95 |
| Fesoterodine 4 mg 20% ER-BIC Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Fesoterodine Metabolite (5-HMT) | 7.59 ng*hr/mL | Standard Deviation 3.57 |
| Fesoterodine 4 mg ER Tablet Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Fesoterodine Metabolite (5-HMT) | 26.80 ng*hr/mL | Standard Deviation 10.07 |
| Fesoterodine 4 mg 10% ER-BIC Fed | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Fesoterodine Metabolite (5-HMT) | 31.88 ng*hr/mL | Standard Deviation 13.24 |
Comparison: Natural log transformed AUClast of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg IR-BIC Fasted was test.90% CI: [103.85, 122.52]
Comparison: Natural log transformed AUClast of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg 10% ER-BIC Fasted was test.90% CI: [95.48, 112.65]
Comparison: Natural log transformed AUClast of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg 15% ER-BIC Fasted was test.90% CI: [61.56, 72.63]
Comparison: Natural log transformed AUClast of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg 20% ER-BIC Fasted was test.90% CI: [26.09, 30.78]
Comparison: Natural log transformed AUClast of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg 10% ER-BIC Fasted was reference and Fesoterodine 4 mg 10% ER-BIC Fed was test.90% CI: [106.99, 122.97]
Primary
Maximum Observed Plasma Concentration (Cmax) for Fesoterodine Metabolite (5-HMT)
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hrs post dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine 4 mg IR-BIC Fasted | Maximum Observed Plasma Concentration (Cmax) for Fesoterodine Metabolite (5-HMT) | 5.830 ng/mL | Standard Deviation 2.729 |
| Fesoterodine 4 mg 10% ER-BIC Fasted | Maximum Observed Plasma Concentration (Cmax) for Fesoterodine Metabolite (5-HMT) | 3.030 ng/mL | Standard Deviation 1.068 |
| Fesoterodine 4 mg 15% ER-BIC Fasted | Maximum Observed Plasma Concentration (Cmax) for Fesoterodine Metabolite (5-HMT) | 1.092 ng/mL | Standard Deviation 0.496 |
| Fesoterodine 4 mg 20% ER-BIC Fasted | Maximum Observed Plasma Concentration (Cmax) for Fesoterodine Metabolite (5-HMT) | 0.323 ng/mL | Standard Deviation 0.183 |
| Fesoterodine 4 mg ER Tablet Fasted | Maximum Observed Plasma Concentration (Cmax) for Fesoterodine Metabolite (5-HMT) | 2.247 ng/mL | Standard Deviation 1 |
| Fesoterodine 4 mg 10% ER-BIC Fed | Maximum Observed Plasma Concentration (Cmax) for Fesoterodine Metabolite (5-HMT) | 5.183 ng/mL | Standard Deviation 1.919 |
Comparison: Natural log transformed Cmax of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg IR-BIC Fasted was test.90% CI: [231.48, 290.7]
Comparison: Natural log transformed Cmax of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg 10% ER-BIC Fasted was test.90% CI: [120.31, 151.09]
Comparison: Natural log transformed Cmax of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg 15% ER-BIC Fasted was test.90% CI: [43.35, 54.44]
Comparison: Natural log transformed Cmax of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg ER Tablet Fasted was reference and Fesoterodine 4 mg 20% ER-BIC Fasted was test.90% CI: [12.83, 16.11]
Comparison: Natural log transformed Cmax of 5-HMT was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Fesoterodine 4 mg 10% ER-BIC Fasted was reference and Fesoterodine 4 mg 10% ER-BIC Fed was test.90% CI: [115.82, 187.78]
Secondary
Plasma Decay Half Life (t1/2) for Fesoterodine Metabolite (5-HMT)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hrs post dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here, the N (number of participants analyzed) is signifying the number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine 4 mg IR-BIC Fasted | Plasma Decay Half Life (t1/2) for Fesoterodine Metabolite (5-HMT) | 5.56 hr | Standard Deviation 1.7 |
| Fesoterodine 4 mg 10% ER-BIC Fasted | Plasma Decay Half Life (t1/2) for Fesoterodine Metabolite (5-HMT) | 7.22 hr | Standard Deviation 1.68 |
| Fesoterodine 4 mg 15% ER-BIC Fasted | Plasma Decay Half Life (t1/2) for Fesoterodine Metabolite (5-HMT) | 10.89 hr | Standard Deviation 4.45 |
| Fesoterodine 4 mg 20% ER-BIC Fasted | Plasma Decay Half Life (t1/2) for Fesoterodine Metabolite (5-HMT) | NA hr | — |
| Fesoterodine 4 mg ER Tablet Fasted | Plasma Decay Half Life (t1/2) for Fesoterodine Metabolite (5-HMT) | 7.54 hr | Standard Deviation 2.49 |
| Fesoterodine 4 mg 10% ER-BIC Fed | Plasma Decay Half Life (t1/2) for Fesoterodine Metabolite (5-HMT) | 4.59 hr | Standard Deviation 0.76 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Fesoterodine Metabolite (5-HMT)
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hrs post dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fesoterodine 4 mg IR-BIC Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Fesoterodine Metabolite (5-HMT) | 1.0 hr |
| Fesoterodine 4 mg 10% ER-BIC Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Fesoterodine Metabolite (5-HMT) | 6.0 hr |
| Fesoterodine 4 mg 15% ER-BIC Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Fesoterodine Metabolite (5-HMT) | 6.0 hr |
| Fesoterodine 4 mg 20% ER-BIC Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Fesoterodine Metabolite (5-HMT) | 8.0 hr |
| Fesoterodine 4 mg ER Tablet Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Fesoterodine Metabolite (5-HMT) | 5.0 hr |
| Fesoterodine 4 mg 10% ER-BIC Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Fesoterodine Metabolite (5-HMT) | 4.0 hr |