Trial Outcomes & Findings for Multiple Dose Study To Investigate The Effects Of Fesoterodine And Solifenacin On Gastrointestinal Transit (NCT NCT00832650)

Last Updated: 2010-12-24

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

60 participants

Primary outcome timeframe

Day 13 (Day 12 24 hours post-meal)

Results posted on

2010-12-24

Participant Flow

Participant milestones

Participant milestones
Measure	Fesoterodine Fesoterodine 8 mg tablet once daily	Placebo Matched placebo tablet or capsule	Solifenacin Solifenacin 10 mg capsule once daily
Overall Study STARTED	25	12	23
Overall Study Treated	25	12	22
Overall Study COMPLETED	25	12	22
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Fesoterodine Fesoterodine 8 mg tablet once daily	Placebo Matched placebo tablet or capsule	Solifenacin Solifenacin 10 mg capsule once daily
Overall Study Randomized but not treated	0	0	1

Baseline Characteristics

Multiple Dose Study To Investigate The Effects Of Fesoterodine And Solifenacin On Gastrointestinal Transit

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=23 Participants Solifenacin 10 mg capsule once daily	Total n=60 Participants Total of all reporting groups
Age, Customized less than 18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Age, Customized 18 to 25 years	5 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	16 participants n=4 Participants
Age, Customized 26 to 35 years	7 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants	15 participants n=4 Participants
Age, Customized 36 to 45 years	7 participants n=5 Participants	2 participants n=7 Participants	8 participants n=5 Participants	17 participants n=4 Participants
Age, Customized greater than 45 years	6 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	12 participants n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants	60 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 13 (Day 12 24 hours post-meal)

Population: Intent to treat (ITT) included all randomized subjects. Imputation by overall mean for missing data.

Outcome measures

Outcome measures
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=23 Participants Solifenacin 10 mg capsule once daily
Colonic Transit at 24 Hours	1.98 counts Standard Deviation 0.770	2.51 counts Standard Deviation 1.078	1.91 counts Standard Deviation 0.515

SECONDARY outcome

Timeframe: Day 12 to 14

Population: ITT included all randomized subjects. Imputation by overall mean for missing data.

Estimated by power exponential analysis of the proportionate emptying over time of counts from the colon.

Outcome measures

Outcome measures
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=23 Participants Solifenacin 10 mg capsule once daily
Proximal Colonic Emptying Time	21.06 hours Standard Deviation 5.500	14.79 hours Standard Deviation 6.239	19.23 hours Standard Deviation 6.194

SECONDARY outcome

Timeframe: Day 14 (Day 12 48 hours post-meal)

Population: ITT included all randomized subjects. Imputation by overall mean for missing data.

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.

Outcome measures

Outcome measures
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=23 Participants Solifenacin 10 mg capsule once daily
Colonic Transit at 48 Hours	3.55 counts Standard Deviation 0.934	3.67 counts Standard Deviation 1.066	3.14 counts Standard Deviation 0.765

SECONDARY outcome

Timeframe: Day 12

Population: ITT included all randomized subjects. Imputation by overall mean for missing data.

A surrogate marker of small bowel transit time.

Outcome measures

Outcome measures
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=23 Participants Solifenacin 10 mg capsule once daily
Colonic Filling at 6 Hours	7.84 percentage Standard Deviation 16.286	69.58 percentage Standard Deviation 25.854	24.06 percentage Standard Deviation 23.696

SECONDARY outcome

Timeframe: Day 12: 2 hours, 4 hours

Population: ITT included all randomized subjects. Imputation by overall mean for missing data.

Ascending colon emptying t½ was estimated by power exponential analysis of the proportionate emptying over time of counts from the colon.

Outcome measures

Outcome measures
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=23 Participants Solifenacin 10 mg capsule once daily
Time to Gastric Emptying	145.00 minutes Standard Deviation 32.628	112.92 minutes Standard Deviation 21.998	127.47 minutes Standard Deviation 35.456

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=22 Participants Solifenacin 10 mg capsule once daily
Mean Number of Stools Per Day	0.93 stools Standard Deviation 0.397	1.06 stools Standard Deviation 0.422	1.11 stools Standard Deviation 0.497

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=22 Participants Solifenacin 10 mg capsule once daily
Mean Score of Stool Consistency Per Day	3.66 score on a scale Standard Deviation 1.149	3.29 score on a scale Standard Deviation 1.112	3.02 score on a scale Standard Deviation 1.057

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=22 Participants Solifenacin 10 mg capsule once daily
Average Score of Ease of Passage During Defecation Per Day	3.90 score on a scale Standard Deviation 0.403	3.97 score on a scale Standard Deviation 0.096	3.83 score on a scale Standard Deviation 0.705

SECONDARY outcome

Timeframe: 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.

The number of stools with satisfaction of "Yes" divided by the total number of stools passed on each notional day. Mean of 3 days.

Outcome measures

Outcome measures
Measure	Fesoterodine n=25 Participants Fesoterodine 8 mg tablet once daily	Placebo n=12 Participants Matched placebo tablet or capsule	Solifenacin n=22 Participants Solifenacin 10 mg capsule once daily
Mean Proportion of Bowel Movements With Satisfaction Per Day	0.88 mean proportion Standard Deviation 0.250	0.81 mean proportion Standard Deviation 0.324	0.93 mean proportion Standard Deviation 0.234

Adverse Events

Fesoterodine

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Solifenacin

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Fesoterodine n=25 participants at risk Fesoterodine 8 mg tablet once daily	Placebo n=12 participants at risk Matched placebo tablet or capsule	Solifenacin n=22 participants at risk Solifenacin 10 mg capsule once daily
Eye disorders Dry eye	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.5% 1/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vision blurred	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.3% 1/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal discomfort	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.3% 1/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 2/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.6% 3/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	8.0% 2/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 2/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	25.0% 3/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.5% 1/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.5% 1/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	8.0% 2/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	52.0% 13/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	31.8% 7/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyschezia	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	25.0% 3/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.5% 1/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.5% 1/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	8.0% 2/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 2/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.6% 3/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.3% 1/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.5% 1/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	48.0% 12/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	25.0% 3/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 2/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Dysuria	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.3% 1/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Pollakiuria	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Dysmenorrhoea	8.0% 2/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.3% 1/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.6% 3/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dry throat	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.0% 1/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.6% 3/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.5% 1/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hot flush	0.00% 0/25 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.5% 1/22 • Up to 7 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.