Trial Outcomes & Findings for Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer (NCT NCT00343382)

Last Updated: 2016-08-12

Results Overview

Vaginal dryness was measured by the numerical analogue scale at baseline and through the six weeks of treatment. The item scores was transformed into 0 to 100 scales with 0=poor quality of life (QOL) and 100=best possible QOL. The average AUC values were calculated by dividing 6 from AUC values for participants who completed item on all 6 weeks. If a participant completed the item at baseline, week 1, 2 and 3 but did not complete the item at week 4 to week 6, the AUC values of the item was prorated, which is (((AUC values \* 6) / 3) / 6). The average pro-rated AUC for vaginal dryness scores was compared in each of the Pilocarpine arms against the collective placebo arm.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

201 participants

Primary outcome timeframe

Baseline to Week 6

Results posted on

2016-08-12

Participant Flow

Two-hundred and one (201) participants were recruited between December 2006 and May 2009 from 22 North Central Cancer Treatment Group (NCCTG) member sites.

Five participants (2 collective placebo, 2 Pilocarpine 2 times per day, 1 Pilocarpine 4 times per day) canceled prior to study medication begins and one Pilocarpine 2 times per day participant was ineligible. These six participants were excluded from all analysis.

Participant milestones

Participant milestones
Measure	Collective Placebo Patients receive 1 capsule of placebo 2 times per day for 6 weeks and; patients receive 1 capsule of placebo 4 times per day for 6 weeks.	Pilocarpine 2 Times Per Day Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Pilocarpine 4 Times Per Day Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Overall Study STARTED	64	65	66
Overall Study COMPLETED	60	51	49
Overall Study NOT COMPLETED	4	14	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Collective Placebo Patients receive 1 capsule of placebo 2 times per day for 6 weeks and; patients receive 1 capsule of placebo 4 times per day for 6 weeks.	Pilocarpine 2 Times Per Day Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Pilocarpine 4 Times Per Day Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Overall Study Adverse Event	2	10	7
Overall Study Withdrawal by Subject	1	2	6
Overall Study Other Reason Not Specified	1	2	4

Baseline Characteristics

Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Collective Placebo n=64 Participants Patients receive 1 capsule of placebo 2 times per day for 6 weeks and; patients receive 1 capsule of placebo 4 times per day for 6 weeks.	Pilocarpine 2 Times Per Day n=65 Participants Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Pilocarpine 4 Times Per Day n=66 Participants Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.	Total n=195 Participants Total of all reporting groups
Age, Continuous	54.6 years STANDARD_DEVIATION 7.93 • n=5 Participants	55.1 years STANDARD_DEVIATION 8.14 • n=7 Participants	54.7 years STANDARD_DEVIATION 7.25 • n=5 Participants	54.8 years STANDARD_DEVIATION 7.74 • n=4 Participants
Sex/Gender, Customized Female	64 participants n=5 Participants	65 participants n=7 Participants	66 participants n=5 Participants	195 participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	60 Participants n=5 Participants	63 Participants n=7 Participants	65 Participants n=5 Participants	188 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	64 participants n=5 Participants	65 participants n=7 Participants	66 participants n=5 Participants	195 participants n=4 Participants
Tamoxifen use Yes	10 participants n=5 Participants	10 participants n=7 Participants	9 participants n=5 Participants	29 participants n=4 Participants
Tamoxifen use No	54 participants n=5 Participants	54 participants n=7 Participants	56 participants n=5 Participants	164 participants n=4 Participants
Tamoxifen use Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Current aromatase inhibitor Yes	36 participants n=5 Participants	37 participants n=7 Participants	38 participants n=5 Participants	111 participants n=4 Participants
Current aromatase inhibitor No	28 participants n=5 Participants	27 participants n=7 Participants	27 participants n=5 Participants	82 participants n=4 Participants
Current aromatase inhibitor Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Severity of vaginal symptoms Mild	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	18 participants n=4 Participants
Severity of vaginal symptoms Moderate	30 participants n=5 Participants	30 participants n=7 Participants	30 participants n=5 Participants	90 participants n=4 Participants
Severity of vaginal symptoms Severe	28 participants n=5 Participants	29 participants n=7 Participants	30 participants n=5 Participants	87 participants n=4 Participants
Breast cancer history Yes	55 participants n=5 Participants	59 participants n=7 Participants	58 participants n=5 Participants	172 participants n=4 Participants
Breast cancer history No	9 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants	23 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 6

Population: Includes all participants that reported a baseline value and at least one value after baseline (i.e. week 3, 4, 5 or 6).

Outcome measures

Outcome measures
Measure	Collective Placebo n=61 Participants Patients receive 1 capsule of placebo 2 times per day for 6 weeks and; patients receive 1 capsule of placebo 4 times per day for 6 weeks.	Pilocarpine 2 Times Per Day n=61 Participants Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Pilocarpine 4 Times Per Day n=55 Participants Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Average Vaginal Dryness Scores Via Area Under the Curve (AUC) Summary Statistics	63.6 units on a scale Standard Deviation 24.04	55.8 units on a scale Standard Deviation 27.69	66.0 units on a scale Standard Deviation 21.38

SECONDARY outcome

Timeframe: End of 6 weeks

CTCAE Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.

Outcome measures

Outcome measures
Measure	Collective Placebo n=63 Participants Patients receive 1 capsule of placebo 2 times per day for 6 weeks and; patients receive 1 capsule of placebo 4 times per day for 6 weeks.	Pilocarpine 2 Times Per Day n=65 Participants Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Pilocarpine 4 Times Per Day n=66 Participants Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0 Grade 1 or 2 urinary frequency	12 participants	21 participants	29 participants
Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0 Grade 1 or 2 sweating	19 participants	29 participants	33 participants
Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0 Grade 1 or 2 nausea	7 participants	16 participants	20 participants
Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0 Grade 1 or 2 rigors	2 participants	14 participants	17 participants

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Includes all participants that reported a baseline value and at least one value after baseline (i.e. week 3, 4, 5 or 6).

The impact of vaginal dryness for activities of daily living (ADL) were measured by the numerical analogue scales at baseline and through the six weeks of treatment. The item scores was transformed into 0 to 100 scales with 0=poor quality of life (QOL) and 100=best possible QOL. The average AUC values were calculated by dividing 6 from AUC values for participants who completed item on all 6 weeks. If a participant completed the item at baseline, week 1, 2 and 3 but did not complete the item at week 4 to week 6, the AUC values of the item was prorated, which is (((AUC values \* 6) / 3) / 6). The average pro-rated AUC scores was compared in each of the Pilocarpine arms against the collective placebo arm.

Outcome measures

Outcome measures
Measure	Collective Placebo n=62 Participants Patients receive 1 capsule of placebo 2 times per day for 6 weeks and; patients receive 1 capsule of placebo 4 times per day for 6 weeks.	Pilocarpine 2 Times Per Day n=61 Participants Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Pilocarpine 4 Times Per Day n=55 Participants Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living Interfered with general activity	87.9 units on a scale Standard Deviation 15.77	87.1 units on a scale Standard Deviation 15.36	87.0 units on a scale Standard Deviation 15.72
Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living Interfered with mood	85.4 units on a scale Standard Deviation 17.17	75.8 units on a scale Standard Deviation 24.16	81.8 units on a scale Standard Deviation 17.65
Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living Interfered with normal work	91.5 units on a scale Standard Deviation 14.08	93.0 units on a scale Standard Deviation 11.77	92.3 units on a scale Standard Deviation 10.80
Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living Interfered with relations with other people	82.2 units on a scale Standard Deviation 20.62	77.9 units on a scale Standard Deviation 25.92	80.6 units on a scale Standard Deviation 21.27
Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living Interfered with sleep	93.0 units on a scale Standard Deviation 13.46	92.3 units on a scale Standard Deviation 15.81	93.3 units on a scale Standard Deviation 9.28
Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living Interfered with enjoyment of life	77.8 units on a scale Standard Deviation 24.24	68.7 units on a scale Standard Deviation 27.84	76.4 units on a scale Standard Deviation 23.08

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Includes all participants who completed both baseline and week 6 assessments.

Outcome measures

Outcome measures
Measure	Collective Placebo n=58 Participants Patients receive 1 capsule of placebo 2 times per day for 6 weeks and; patients receive 1 capsule of placebo 4 times per day for 6 weeks.	Pilocarpine 2 Times Per Day n=58 Participants Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Pilocarpine 4 Times Per Day n=54 Participants Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.
Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores Interfered with general activity	17.8 units on a scale Standard Deviation 26.23	16.0 units on a scale Standard Deviation 28.77	16.1 units on a scale Standard Deviation 27.02
Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores Interfered with mood	18.3 units on a scale Standard Deviation 29.03	17.8 units on a scale Standard Deviation 29.44	18.9 units on a scale Standard Deviation 34.62
Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores Interfered with normal work	11.0 units on a scale Standard Deviation 23.15	6.0 units on a scale Standard Deviation 18.16	9.1 units on a scale Standard Deviation 22.17
Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores Interfered with relations with other people	23.0 units on a scale Standard Deviation 37.41	18.5 units on a scale Standard Deviation 33.02	24.3 units on a scale Standard Deviation 41.15
Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores Interfered with sleep	5.6 units on a scale Standard Deviation 19.27	5.1 units on a scale Standard Deviation 12.75	10.8 units on a scale Standard Deviation 21.99
Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores Interfered with enjoyment of life	26.7 units on a scale Standard Deviation 35.17	21.1 units on a scale Standard Deviation 36.11	30.2 units on a scale Standard Deviation 33.14

Adverse Events

Pilocarpine 2 Times Per Day

Serious events: 0 serious events

Other events: 48 other events

Deaths: 0 deaths

Pilocarpine 4 Times Per Day

Serious events: 0 serious events

Other events: 47 other events

Deaths: 0 deaths

Collective Placebo

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Charles L. Loprinzi

Mayo Clinic

Phone: 507-284-1623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pilocarpine 2 Times Per Day n=65 participants at risk Patients receive 5mg of Pilocarpine 2 times per day for 6 weeks.	Pilocarpine 4 Times Per Day n=66 participants at risk Patients receive 5mg of Pilocarpine 4 times per day for 6 weeks.	Collective Placebo n=63 participants at risk Patients receive 1 capsule of placebo 2 times per day for 6 weeks and; patients receive 1 capsule of placebo 4 times per day for 6 weeks.
Eye disorders Flashing vision	1.5% 1/65 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/66 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Gastrointestinal disorders Abdominal distension	1.5% 1/65 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/66 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Gastrointestinal disorders Diarrhea	0.00% 0/65 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	1.5% 1/66 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Gastrointestinal disorders Dry mouth	0.00% 0/65 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/66 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	1.6% 1/63 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Gastrointestinal disorders Flatulence	1.5% 1/65 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/66 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/65 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	4.5% 3/66 • Number of events 3 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	1.6% 1/63 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Gastrointestinal disorders Nausea	24.6% 16/65 • Number of events 16 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	30.3% 20/66 • Number of events 20 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	11.1% 7/63 • Number of events 7 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Gastrointestinal disorders Salivary gland disorder	0.00% 0/65 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	3.0% 2/66 • Number of events 2 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
General disorders Rigors	21.5% 14/65 • Number of events 14 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	25.8% 17/66 • Number of events 17 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	3.2% 2/63 • Number of events 2 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
General disorders General symptom	1.5% 1/65 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/66 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Nervous system disorders Dizziness	15.4% 10/65 • Number of events 10 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	19.7% 13/66 • Number of events 13 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	9.5% 6/63 • Number of events 6 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Nervous system disorders Headache	1.5% 1/65 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/66 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Renal and urinary disorders Urinary frequency	32.3% 21/65 • Number of events 21 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	43.9% 29/66 • Number of events 29 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	19.0% 12/63 • Number of events 12 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	32.3% 21/65 • Number of events 21 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	37.9% 25/66 • Number of events 25 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	22.2% 14/63 • Number of events 14 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Skin and subcutaneous tissue disorders Pruritus	1.5% 1/65 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/66 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Skin and subcutaneous tissue disorders Rash desquamating	1.5% 1/65 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/66 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Skin and subcutaneous tissue disorders Sweating	44.6% 29/65 • Number of events 29 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	50.0% 33/66 • Number of events 33 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	30.2% 19/63 • Number of events 19 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.
Skin and subcutaneous tissue disorders Urticaria	1.5% 1/65 • Number of events 1 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/66 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.	0.00% 0/63 • End of 6 Weeks Adverse event information at end of 6 weeks is not available on one participant from collective placebo arm.