Trial Outcomes & Findings for Vaginal Testosterone Cream vs ESTRING for Vaginal Dryness or Decreased Libido in Early Stage Breast Cancer Patients (NCT NCT00698035)

NCT ID: NCT00698035

Last Updated: 2014-06-02

Results Overview

Liquid chromatography tandem mass spectrometry (Quest Diagnostics). Persistently elevated serum estradiol level outside the post-menopausal range was defined as: Serum estradiol \>10 pg/dl on two consecutive collections at least 4 weeks apart. 2. If baseline estradiol was \>10 pg/dl, subsequent levels \>10 pg/ml higher than baseline were considered a significant elevation outside the post-menopausal range.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 76 participants
• Primary outcome timeframe: 12 Weeks
• Results posted on: 2014-06-02

Participant Flow

Of 76 enrolled participants, one participant consented and was assigned to ESTRING, but did not insert ESTRING prior to withdrawing from the study.

Participant milestones

Measure	Estring Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment
Overall Study STARTED	39	36
Overall Study COMPLETED	35	34
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vaginal Testosterone Cream vs ESTRING for Vaginal Dryness or Decreased Libido in Early Stage Breast Cancer Patients

Baseline characteristics by cohort

Measure	Estring n=39 Participants Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream n=36 Participants Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment	Total n=75 Participants Total of all reporting groups
Age, Continuous	56 years n=5 Participants	57 years n=7 Participants	56 years n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	36 Participants n=7 Participants	75 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	39 participants n=5 Participants	36 participants n=7 Participants	75 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 Weeks

Population: Per protocol, to be considered evaluable for the Primary Outcome, patients must complete both baseline evaluation and week 4 safety blood draw. 1 participant in the Testosterone arm was not evaluable.

Liquid chromatography tandem mass spectrometry (Quest Diagnostics). Persistently elevated serum estradiol level outside the post-menopausal range was defined as: Serum estradiol >10 pg/dl on two consecutive collections at least 4 weeks apart. 2. If baseline estradiol was >10 pg/dl, subsequent levels >10 pg/ml higher than baseline were considered a significant elevation outside the post-menopausal range.

Outcome measures

Measure	Estring n=35 Participants Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream n=33 Participants Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment
Persistently Elevated Serum Estradiol Level Outside the Post-menopausal Range	0 participants	4 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol, participants who completed 12 weeks of assigned treatment

serial measurements of serum estradiol (E2) by liquid chromatography tandem mass spectrometry (Quest Diagnostics)

Outcome measures

Measure	Estring n=35 Participants Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream n=34 Participants Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment
Serum Estradiol (E2) E2 at 4 weeks	5 pg/ml Standard Deviation 5	10 pg/ml Standard Deviation 20
Serum Estradiol (E2) E2 at baseline	27 pg/ml Standard Deviation 36	9 pg/ml Standard Deviation 13
Serum Estradiol (E2) E2 at 12 weeks	9 pg/ml Standard Deviation 12	8 pg/ml Standard Deviation 7

SECONDARY outcome

Timeframe: baseline, 4 weeks

Population: Patients from both study arms arms with matched pairs of baseline and week 4 E2 performed by both commercial and research labs

Serum estradiol assays sent to the UCSF clinical laboratory are sent out to Quest Diagnostics, which uses LC/MS for their ultra-sensitive estradiol assay. Samples were also sent to a specialized research lab in England which has developed an ultrasensitive assay using radioimmunoassay (RIA) after ether extraction (sensitivity limit of 3pmol/l) to quantify low levels of estradiol found in post-menopausal women

Outcome measures

Measure	Estring n=63 Participants Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream n=63 Participants Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment
Matched E2 by Commercial and Research (RIA) Analyses Baseline E2	17.7 pg/ml Standard Deviation 28.5	17.9 pg/ml Standard Deviation 44.1
Matched E2 by Commercial and Research (RIA) Analyses 4-week E2	7.8 pg/ml Standard Deviation 15.0	2.9 pg/ml Standard Deviation 13.4

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol, participants assigned to the Testosterone arm who completed 12 weeks of assigned treatment and had testosterone measurement at baseline, 4 weeks and 12 weeks.

By serum ultrasensitive total testosterone test (Quest Diagnostics)

Outcome measures

Measure	Estring n=27 Participants Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment
Total Testosterone Levels Testosterone at baseline	33 ng/dl Standard Deviation 19	—
Total Testosterone Levels Testosterone at 4 weeks	186 ng/dl Standard Deviation 276	—
Total Testosterone Levels Testosterone at 12 weeks	171 ng/dl Standard Deviation 251	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 12

Population: Participants who provided responses to SD, SI and SS at 3 time points: Baseline (BL), Week 4 (W4), and Week 12 (W12)

Cancer Rehabilitation Evaluation System (CARES) Sexual Dysfunction (SD) and Sexual Interest (SI) Subscales range from 0 to 4 and measure the severity of problems, with higher scores indicating more difficulty.

Outcome measures

Measure	Estring n=32 Participants Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream n=30 Participants Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment
Sexual Quality of Life SI (BL)	1.2 units on a scale Standard Deviation 0.9	1.4 units on a scale Standard Deviation 0.8
Sexual Quality of Life SI (W4)	1.3 units on a scale Standard Deviation 1.0	1.2 units on a scale Standard Deviation 0.7
Sexual Quality of Life SI (W12)	0.9 units on a scale Standard Deviation 0.7	1.0 units on a scale Standard Deviation 0.6
Sexual Quality of Life SD (BL)	2.9 units on a scale Standard Deviation 1.1	2.9 units on a scale Standard Deviation 0.8
Sexual Quality of Life SD (W4)	2.4 units on a scale Standard Deviation 1.1	2.1 units on a scale Standard Deviation 1.0
Sexual Quality of Life SD (W12)	2.0 units on a scale Standard Deviation 1.1	1.9 units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 12

Population: Participants who provided responses to SD, SI and SS at all 3 time points: Baseline (BL), Week 4 (W4), and Week 12 (W12)

Participants were asked to respond to a Sexual Satisfaction One Item Measure which asked "Overall, how satisfactory to you is your sexual relationship with your partner?" Response options range from 1 (Extremely unsatisfactory) to 6 (Extremely satisfactory).

Outcome measures

Measure	Estring n=32 Participants Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream n=30 Participants Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment
Sexual Satisfaction SS (BL)	2.5 units on a scale Standard Deviation 1.6	3.2 units on a scale Standard Deviation 1.6
Sexual Satisfaction SS (W4)	3.5 units on a scale Standard Deviation 1.8	3.7 units on a scale Standard Deviation 1.6
Sexual Satisfaction SS (W12)	4.0 units on a scale Standard Deviation 1.5	4.0 units on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Patients with both baseline and week 12 gynecologic exams for evaluation of vaginal atrophy

During a gynecologic exam, the vaginal epithelium was assessed by an examiner using the Vaginal Atrophy Scoring Scale to evaluate Rugae (lack of), Pallor (pinkness), Petechiae, Mucosal thinning, Dryness. Scores range from 0 (none) to 3 (severe); higher scores indicate less favorable outcomes.

Outcome measures

Measure	Estring n=35 Participants Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream n=34 Participants Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment
Change in Vaginal Epithelium Scores Rugae	-1.03 units on a scale Standard Deviation 0.80	-0.71 units on a scale Standard Deviation 0.84
Change in Vaginal Epithelium Scores Pallor	-0.88 units on a scale Standard Deviation 0.84	-0.91 units on a scale Standard Deviation 0.75
Change in Vaginal Epithelium Scores Petechiae	-1.0 units on a scale Standard Deviation 1.07	-0.74 units on a scale Standard Deviation 1.38
Change in Vaginal Epithelium Scores Mucosal thinning	-0.62 units on a scale Standard Deviation 0.49	-0.88 units on a scale Standard Deviation 0.64
Change in Vaginal Epithelium Scores Dryness	-1.03 units on a scale Standard Deviation 0.80	-0.71 units on a scale Standard Deviation 0.91

Adverse Events

Estring

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Testosterone Cream

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Estring n=39 participants at risk Estring 2mg ring inserted vaginally once every 12 weeks	Testosterone Cream n=36 participants at risk Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment
Reproductive system and breast disorders Vaginal discharge	10.3% 4/39 • Number of events 4 • 12 weeks	5.6% 2/36 • Number of events 2 • 12 weeks
Skin and subcutaneous tissue disorders Facial hair growth	2.6% 1/39 • Number of events 1 • 12 weeks	13.9% 5/36 • Number of events 5 • 12 weeks
General disorders Hot flashes	7.7% 3/39 • Number of events 3 • 12 weeks	2.8% 1/36 • Number of events 1 • 12 weeks
Reproductive system and breast disorders Vaginal itching or irritation	10.3% 4/39 • Number of events 4 • 12 weeks	0.00% 0/36 • 12 weeks
Reproductive system and breast disorders Vaginal odor	0.00% 0/39 • 12 weeks	8.3% 3/36 • Number of events 3 • 12 weeks

Additional Information

Michelle Melisko, MD

University of California, San Francisco

Phone: 415-353-7070

Email: mmelisko@medicine.ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place