Clinical Trials Register

Summary
EudraCT Number:	2021-004536-28
Sponsor's Protocol Code Number:	1
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-09-16
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2021-004536-28

A.3

Full title of the trial

Vaginal administration of selective estrogen receptor modulator (Tamoxifen) treatment to improve sexual function for women with breast cancer. A randomized, double-blinded, placebo controlled longitudinal phase 3 study.

Vaginal behandling med selektiv östrogenreceptormodulerare (Tamoxifen) för förbättrad sexuell funktion hos kvinnor med bröstcancer. En randomiserad, dubbelblindad, placebokontrollerad longitudinell fas 3 studie.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.4.1

Sponsor's protocol code number

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Uppsala University, Department of Women's and Children´s Health
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Uppsala universitet
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Uppsala university
B.5.2	Functional name of contact point	Women's and Children's Health
B.5.3	Address:
B.5.3.1	Street Address	Akademiska sjukhuset
B.5.3.2	Town/ city	Uppsala
B.5.3.3	Post code	75185
B.5.3.4	Country	Sweden
B.5.4	Telephone number	46702465156
B.5.6	E-mail	inger.sundstrom@kbh.uu.se

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tamoxifen Sandoz
D.2.1.1.2	Name of the Marketing Authorisation holder	Sandoz AS
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tamoxifen Sandoz
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Vaginal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tamoxifen
D.3.9.1	CAS number	54965-24-1
D.3.9.3	Other descriptive name	TAMOXIFEN CITRATE
D.3.9.4	EV Substance Code	SUB04672MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Vaginal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Most troublesome vulvovaginal atrophy symptom

E.1.1.1

Medical condition in easily understood language

Most troublesome vulvovaginal atrophy symptom

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Improvement of most troublesome vulvovaginal atrophy symptom. At randomization, the severity of the most troublesome VVA symptom will be noted and improvement of the most troublesome VVA, yes/no, a dichotomized variable will be the primary endpoint.

E.2.2

Secondary objectives of the trial

Overall sexual function

objective parameters for improved vuvlvovaginal atrophy such as vaginal pH, percentage superficial and parabasal cells

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Sexually active postmenopausal women with breast cancer and ongoing adjuvant antiestrogen treatment with aromatase inhibitors who are willing to participate in the study and give their written consent.
2. Postmenopausal women with at least 12 months of spontaneous amenorrhea, or women who have had surgical bilateral oophorectomy at least 6 weeks ago, or level of follicle stimulating hormone (FSH) > 40 mIU/mL.
3. Have a vaginal pH > 5.0 at screening.
5. Have estradiol levels below the detection level, < 20 pmol/l.
6. Have one moderate to severe vulvovaginal atrophy symptom on the FACT-B scale that has been identified by the subject as being the most bothersome to her.
7. Be judged by the principal investigator as being in otherwise good health. The medical evaluation findings must include:
a. A normal or clinically non-significant finding at physical examination.
b. A mean sitting systolic blood pressure ≤150 mm Hg and diastolic blood pressure ≤90 mm Hg at screening.
c. A normal or clinically non-significant finding at gynecological examination.
d. A normal mammography that has been performed within 36 months prior to initial dose of study medication.
e. Laboratory values within normal limits or with non-significant deviations from normal values.
8. Have an endometrial thickness of < 4 mm as determined by vaginal ultrasonography, in women with an intact uterus.

E.4

Principal exclusion criteria

Postmenopausal women with breast cancer and ongoing adjuvant antiestrogen treatment with oral tamoxifen.

In addition, women meeting any of the following criteria will not be permitted to enter the study:
1. Have a history of cardiovascular disease or thromboembolic events.
2. Have a history of or ongoing hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, neurologic, psychological, or musculoskeletal disease or disorder that is clinically significant in the opinion of the principal investigator.
3. Have a history of endometrial hyperplasia, endometrial polyps, endometrial cancer, or ovarian cancer.
4. Have a history of undiagnosed vaginal bleeding.
5. Have an ongoing urogenital infection in spite of treatment at the randomization visit.
6. Have used estrogen alone or estrogen/progestin for any of the following time periods: a. Vaginal hormonal products (rings, creams, gels, vaginal suppositories) within 12 weeks prior to the screening visit;

E.5 End points

E.5.1

Primary end point(s)

Change from baseline to week 12 in severity of most troublesome VVA symptom measured with Endocrine Subscale-FACT-B. At randomization, the severity of the most troublesome VVA symptom will be noted and improvement of the most troublesome VVA, yes/no, a dichotomized variable will be the primary endpoint.

E.5.1.1

Timepoint(s) of evaluation of this end point

4 and 12 weeks of treatment

E.5.2

Secondary end point(s)

• Change from baseline to week 12 in all subscales of the modified version of the Endocrine Subscale-FACT-B
• Change from baseline to week 4 and 12 in total score FSFI.
• Change from baseline to week 4 and 12 in total score on the FSDS-R
• Change from baseline to Week 4 and 12 in Quality of Life collected using the EORTC QLQ-C30.
• Change from baseline to Week 4 and 12 scores in HADS.
• Change from baseline to Week 4 and 12 in vaginal pH, percentage superficial cells (increase is positive), percentage parabasal cells (decrease is positive), and vaginal maturation index (increase is positive).
• Change from baseline to Week 4 and 12 in vaginal pH, percentage superficial cells (increase is positive), percentage parabasal cells (decrease is positive), and vaginal maturation index (increase is positive).

Secondary safety endpoints
• Change from baseline to week 12 in endometrial thickness as determined by vaginal ultrasonography.
• Hyperplasia on endometrial biopsy
• Change from baseline to week 12 in estradiol, Follicle stimulating hormone, tamoxifen, and endoxifen serum concentrations.
• Change from baseline over time of clinical safety data: adverse events, vital signs, physical examination findings, gynecological examination findings, breast examination findings, and laboratory tests.

E.5.2.1

Timepoint(s) of evaluation of this end point

4 and 12 weeks of treament

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

At the last study visit, patients will meet with the study physicia. Treatment for vulvovaginal atrophy symptoms will be provided post trial according to national guidelines.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-11-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-10-22

P. End of Trial
P.	End of Trial Status	Ongoing

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