Healthy
Conditions
Keywords
Healthy; Fesoterodine; Solifenacin
Brief summary
To assess the effect of fesoterodine 8 mg as compared to solifenacin 10 mg on colonic transit.
Interventions
8 mg OD for 14 days
DRUGplacebo
OD for 14 days
DRUGsolifenacin
10 mg OD for 14 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy female subjects
Exclusion criteria
* Evidence or history of clinically significant findings at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Colonic Transit at 24 Hours | Day 13 (Day 12 24 hours post-meal) | Colonic transit: Geometric centre at 24 hours (GC24) was estimated using geometric mean of counts in ascending (AC), transverse (TC), descending (DC) and rectosigmoid (RS) colon and stool (weighted by factors of 1 to 5 respectively). To calculate the geometric centre, the proportion of colonic counts in each colonic region was multiplied by its weighing factor: (% AC \*1 + % TC \*2 + % DC \*3 + % RS \*4 + % stool \* 5 ) divided by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Colonic Transit at 48 Hours | Day 14 (Day 12 48 hours post-meal) | Colonic transit: Geometric centre at 48 hours (GC48) was estimated using geometric mean of counts in ascending (AC), transverse (TC), descending (DC) and rectosigmoid (RS) colon and stool (weighted by factors of 1 to 5 respectively). To calculate the geometric centre, the proportion of colonic counts in each colonic region was multiplied by its weighing factor: (% AC \*1 + % TC \*2 + % DC \*3 + % RS \*4 + % stool \* 5 ) divided by 100. |
| Colonic Filling at 6 Hours | Day 12 | A surrogate marker of small bowel transit time. |
| Time to Gastric Emptying | Day 12: 2 hours, 4 hours | Ascending colon emptying t½ was estimated by power exponential analysis of the proportionate emptying over time of counts from the colon. |
| Proximal Colonic Emptying Time | Day 12 to 14 | Estimated by power exponential analysis of the proportionate emptying over time of counts from the colon. |
| Mean Score of Stool Consistency Per Day | Day 11 to 13 | Calculated by averaging the values of the stool form given at each visit to the toilet on each notional day. Mean of 3 days. Range of possible scores: 1 (hard lumps) to 7 (watery). |
| Average Score of Ease of Passage During Defecation Per Day | Day 11 to 13 | Calculated by averaging the values given for the ease of passage at each visit to the toilet on each notional day. Mean of 3 days. Range of possible scores: 1 (Manual disimpaction) to 7 (Incontinent). |
| Mean Proportion of Bowel Movements With Satisfaction Per Day | Day 11 to 13 | The number of stools with satisfaction of Yes divided by the total number of stools passed on each notional day. Mean of 3 days. |
| Mean Number of Stools Per Day | Day 11 to 13 | Number of stools passed on each notional day where each visit to the toilet counts as one stool (only) unless nothing is passed. Mean of 3 days. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fesoterodine Fesoterodine 8 mg tablet once daily | 25 |
| Placebo Matched placebo tablet or capsule | 12 |
| Solifenacin Solifenacin 10 mg capsule once daily | 23 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Randomized but not treated | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Fesoterodine | Placebo | Solifenacin |
|---|---|---|---|---|
| Age, Customized 18 to 25 years | 16 participants | 5 participants | 5 participants | 6 participants |
| Age, Customized 26 to 35 years | 15 participants | 7 participants | 2 participants | 6 participants |
| Age, Customized 36 to 45 years | 17 participants | 7 participants | 2 participants | 8 participants |
| Age, Customized greater than 45 years | 12 participants | 6 participants | 3 participants | 3 participants |
| Age, Customized less than 18 years | 0 participants | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 60 Participants | 25 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 25 | 6 / 12 | 15 / 22 |
| serious Total, serious adverse events | 0 / 25 | 0 / 12 | 0 / 22 |
Outcome results
Primary
Colonic Transit at 24 Hours
Colonic transit: Geometric centre at 24 hours (GC24) was estimated using geometric mean of counts in ascending (AC), transverse (TC), descending (DC) and rectosigmoid (RS) colon and stool (weighted by factors of 1 to 5 respectively). To calculate the geometric centre, the proportion of colonic counts in each colonic region was multiplied by its weighing factor: (% AC \*1 + % TC \*2 + % DC \*3 + % RS \*4 + % stool \* 5 ) divided by 100.
Time frame: Day 13 (Day 12 24 hours post-meal)
Population: Intent to treat (ITT) included all randomized subjects. Imputation by overall mean for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Colonic Transit at 24 Hours | 1.98 counts | Standard Deviation 0.77 |
| Placebo | Colonic Transit at 24 Hours | 2.51 counts | Standard Deviation 1.078 |
| Solifenacin | Colonic Transit at 24 Hours | 1.91 counts | Standard Deviation 0.515 |
Comparison: Null H10: μF8mg=μS10mg where μF8mg and μS10mg are means of GC24 for fesoterodine 8mg and solifenacin 10mg, respectively.95% CI: [-0.334, 0.436]ANCOVA
Secondary
Average Score of Ease of Passage During Defecation Per Day
Calculated by averaging the values given for the ease of passage at each visit to the toilet on each notional day. Mean of 3 days. Range of possible scores: 1 (Manual disimpaction) to 7 (Incontinent).
Time frame: Day 11 to 13
Population: ITT, all randomized subjects with analyzeable data. Imputation by individual mean for missing data if at least one observation was observed in last 3 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Average Score of Ease of Passage During Defecation Per Day | 3.90 score on a scale | Standard Deviation 0.403 |
| Placebo | Average Score of Ease of Passage During Defecation Per Day | 3.97 score on a scale | Standard Deviation 0.096 |
| Solifenacin | Average Score of Ease of Passage During Defecation Per Day | 3.83 score on a scale | Standard Deviation 0.705 |
Secondary
Colonic Filling at 6 Hours
A surrogate marker of small bowel transit time.
Time frame: Day 12
Population: ITT included all randomized subjects. Imputation by overall mean for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Colonic Filling at 6 Hours | 7.84 percentage | Standard Deviation 16.286 |
| Placebo | Colonic Filling at 6 Hours | 69.58 percentage | Standard Deviation 25.854 |
| Solifenacin | Colonic Filling at 6 Hours | 24.06 percentage | Standard Deviation 23.696 |
Secondary
Colonic Transit at 48 Hours
Colonic transit: Geometric centre at 48 hours (GC48) was estimated using geometric mean of counts in ascending (AC), transverse (TC), descending (DC) and rectosigmoid (RS) colon and stool (weighted by factors of 1 to 5 respectively). To calculate the geometric centre, the proportion of colonic counts in each colonic region was multiplied by its weighing factor: (% AC \*1 + % TC \*2 + % DC \*3 + % RS \*4 + % stool \* 5 ) divided by 100.
Time frame: Day 14 (Day 12 48 hours post-meal)
Population: ITT included all randomized subjects. Imputation by overall mean for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Colonic Transit at 48 Hours | 3.55 counts | Standard Deviation 0.934 |
| Placebo | Colonic Transit at 48 Hours | 3.67 counts | Standard Deviation 1.066 |
| Solifenacin | Colonic Transit at 48 Hours | 3.14 counts | Standard Deviation 0.765 |
Secondary
Mean Number of Stools Per Day
Number of stools passed on each notional day where each visit to the toilet counts as one stool (only) unless nothing is passed. Mean of 3 days.
Time frame: Day 11 to 13
Population: ITT, all randomized subjects with analyzeable data. Imputation by individual mean for missing data if at least one observation was observed in last 3 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Mean Number of Stools Per Day | 0.93 stools | Standard Deviation 0.397 |
| Placebo | Mean Number of Stools Per Day | 1.06 stools | Standard Deviation 0.422 |
| Solifenacin | Mean Number of Stools Per Day | 1.11 stools | Standard Deviation 0.497 |
Secondary
Mean Proportion of Bowel Movements With Satisfaction Per Day
The number of stools with satisfaction of Yes divided by the total number of stools passed on each notional day. Mean of 3 days.
Time frame: Day 11 to 13
Population: ITT, all randomized subjects with analyzeable data. Imputation by individual mean for missing data if at least one observation was observed in last 3 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Mean Proportion of Bowel Movements With Satisfaction Per Day | 0.88 mean proportion | Standard Deviation 0.25 |
| Placebo | Mean Proportion of Bowel Movements With Satisfaction Per Day | 0.81 mean proportion | Standard Deviation 0.324 |
| Solifenacin | Mean Proportion of Bowel Movements With Satisfaction Per Day | 0.93 mean proportion | Standard Deviation 0.234 |
Secondary
Mean Score of Stool Consistency Per Day
Calculated by averaging the values of the stool form given at each visit to the toilet on each notional day. Mean of 3 days. Range of possible scores: 1 (hard lumps) to 7 (watery).
Time frame: Day 11 to 13
Population: ITT, all randomized subjects with analyzeable data. Imputation by individual mean for missing data if at least one observation was observed in last 3 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Mean Score of Stool Consistency Per Day | 3.66 score on a scale | Standard Deviation 1.149 |
| Placebo | Mean Score of Stool Consistency Per Day | 3.29 score on a scale | Standard Deviation 1.112 |
| Solifenacin | Mean Score of Stool Consistency Per Day | 3.02 score on a scale | Standard Deviation 1.057 |
Secondary
Proximal Colonic Emptying Time
Estimated by power exponential analysis of the proportionate emptying over time of counts from the colon.
Time frame: Day 12 to 14
Population: ITT included all randomized subjects. Imputation by overall mean for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Proximal Colonic Emptying Time | 21.06 hours | Standard Deviation 5.5 |
| Placebo | Proximal Colonic Emptying Time | 14.79 hours | Standard Deviation 6.239 |
| Solifenacin | Proximal Colonic Emptying Time | 19.23 hours | Standard Deviation 6.194 |
Secondary
Time to Gastric Emptying
Ascending colon emptying t½ was estimated by power exponential analysis of the proportionate emptying over time of counts from the colon.
Time frame: Day 12: 2 hours, 4 hours
Population: ITT included all randomized subjects. Imputation by overall mean for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Time to Gastric Emptying | 145.00 minutes | Standard Deviation 32.628 |
| Placebo | Time to Gastric Emptying | 112.92 minutes | Standard Deviation 21.998 |
| Solifenacin | Time to Gastric Emptying | 127.47 minutes | Standard Deviation 35.456 |