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Clinical Trial Results:
A Phase 2b, Double-blind, Randomized, Parallel, Placebo-Controlled Study to Evaluate the 12-week Efficacy of Vagitocin in Postmenopausal Women with Symptoms of Vulvovaginal Atrophy

Summary
EudraCT number	2016-000158-36
Trial protocol	SE
Global end of trial date	03 May 2017

Results information
Results version number	v1(current)
This version publication date	08 Nov 2020
First version publication date	08 Nov 2020
Other versions
Summary report(s)	2016-000158-36, OXYPEP202, Study Report Summary

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

OXYPEP202

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

PEPTONIC medical AB

Sponsor organisation address

Gustavslundsvägen 143, Bromma, Sweden, 16751

Public contact

Dan Markusson, PEPTONIC medical AB, 46 853020110, dan.markusson@peptonicmedical.se

Scientific contact

Dan Markusson, PEPTONIC medical AB, 46 853020110, dan.markusson@peptonicmedical.se

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

22 Jun 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 May 2017

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of Vagitocin in reducing the severity of the most bothersome symptom of vulvovaginal atrophy (VVA) associated with menopause after 12 weeks of treatment.

Protection of trial subjects

The study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki that are consistent with International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) and applicable regulatory requirements.

Background therapy

Prior and concomitant medications was collected at Screening and throughout the study. Any hormonal therapy taken within 1 year prior to the Screening visit was recorded as a prior medication with the corresponding indication. Any other medication and dietary supplements taken within 12 weeks prior to the initial administration of the Screening visit were also recorded as prior medications. Concomitant medications included any medication including OTC products and herbal or nutritional supplements/medications taken during the active study period. The investigator or designee assessed changes in concomitant medications throughout the study by asking the subject at each visit and, when appropriate, during

Evidence for comparator

Actual start date of recruitment

02 May 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Sweden: 202

Worldwide total number of subjects

202

EEA total number of subjects

202

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

193

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

First subject was screened on 2016-04-19. A total of 211 women were screened. 161 were randomised in the main part of the study, which was conducted at 3 centres in Sweden. Last subject last visit was 2017-02-15

Screening details

Patients fulfilling all of the inclusion criteria and none of the exclusion criteria were to be asked to participate in the trial. A total of 211 women were screened and 161 were randomised in the main part of the study. Forty-one subjects were screen failures.

Period 1 title

Main part

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

This was a double-blind study, and therefore, subjects, the investigator, study site personnel, and Sponsor personnel involved with data review and analysis, remained blinded to study treatment throughout the study. The packaging of Vagitocin and placebo was identical in appearance to maintain adequate blinding of study subjects and investigators. Neither the subject nor the investigator could identify the treatment from the packaging or label of the IMP..

Are arms mutually exclusive

Yes

Vagitocin 400 IU

Arm description

Vagitocin 400 IU vaginal gel

Arm type

Experimental

Investigational medicinal product name

Vagitocin 400 IU vaginal gel

Investigational medicinal product code

Other name

Pharmaceutical forms

Vaginal gel

Routes of administration

Vaginal use

Dosage and administration details

Vagitocin 400 IU/g vaginal gel, 1 mL administered once daily for 12 weeks.

Placebo

Arm description

Placebo vaginal gel

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Vaginal gel

Routes of administration

Vaginal use

Dosage and administration details

Vaginal gel (placebo), 1 mL administered once daily for 12 weeks.

Number of subjects in period 1 ^[1]	Vagitocin 400 IU	Placebo
Started	81	80
Completed	78	79
Not completed	3	1
Consent withdrawn by subject	-	1
Adverse event, non-fatal	3	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The study includes 2 parts, the main part and the exploratory part. Subjects were included in either the main part or the exploratory part, not in both parts. Thus, the exploratory part is not a continuation of the main part but a separate part. The total number of subjects in the study (202) includes subjects from both parts of the study (main part 161 subjects and 41 subjects).

Period 2 title

Exploratory part

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Monitor, Data analyst, Carer, Assessor, Subject

Blinding implementation details

Are arms mutually exclusive

Yes

Vagitocin 400 IU

Arm description

Vagitocin 400 IU vaginal gel

Arm type

Experimental

Investigational medicinal product name

Vagitocin 400 IU vaginal gel

Investigational medicinal product code

Other name

Pharmaceutical forms

Vaginal gel

Routes of administration

Vaginal use

Dosage and administration details

Vagitocin 400 IU/g vaginal gel, 1 mL administered once daily for 12 weeks.

Placebo

Arm description

Placebo vaginal gel

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Vaginal gel

Routes of administration

Vaginal use

Dosage and administration details

Vaginal gel (placebo), 1 mL administered once daily for 12 weeks.

Number of subjects in period 2 ^[2]	Vagitocin 400 IU	Placebo
Started	31	10
Completed	30	9
Not completed	1	1
Adverse event, non-fatal	1	1

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The study includes 2 parts, the main part and the exploratory part. Subjects were included in either the main part or the exploratory part, not in both parts. Thus, the exploratory part is not a continuation of the main part but a separate part. The total number of subjects in the study (202) includes subjects from both parts of the study (main part 161 subjects and 41 subjects).

Baseline characteristics

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Reporting group title

Main part

Reporting group description

Females aged 40-65 years who were either postmenopausal or had undergone surgical bilateral oophorectomy, with ≤5% superficial cells in vaginal smear cytology, a vaginal pH >5.0, a body mass index (BMI) ≤32 kg/m2, an endometrial thickness of <4 mm and one moderate to severe VVA symptom but who were otherwise in good health and had provided signed informed consent were considered eligible to participate in the study.

Reporting group values	Main part	Total
Number of subjects	161	161
Age categorical
Females aged 40-65 years who were either postmenopausal or had undergone surgical bilateral oophorectomy, with ≤5% superficial cells in vaginal smear cytology, a vaginal pH >5.0, a body mass index (BMI) ≤32 kg/m2, an endometrial thickness of <4 mm and one moderate to severe VVA symptom but who were otherwise in good health and had provided signed informed consent were considered eligible to participate in the study.
Units: Subjects
Adults (18-64 years)	150	150
From 65-84 years	11	11
Age continuous
Females aged 40-65 years who were either postmenopausal or had undergone surgical bilateral oophorectomy, with ≤5% superficial cells in vaginal smear cytology, a vaginal pH >5.0, a body mass index (BMI) ≤32 kg/m2, an endometrial thickness of <4 mm and one moderate to severe VVA symptom but who were otherwise in good health and had provided signed informed consent were considered eligible to participate in the study.
Units: years
arithmetic mean (standard deviation)	58.3 ( 3.5 )	-
Gender categorical
Females aged 40-65 years
Units: Subjects
Female	161	161
Race
Units: Subjects
Caucasian	159	159
Other	2	2
Use of tobacco
Units: Subjects
Never	93	93
Current	7	7
Former	60	60
Missing	1	1
Alcohol consumption
Units: Subjects
Never	17	17
Current	144	144
Height
Units: cm
arithmetic mean (standard deviation)	165.9 ( 5.8 )	-
Weight
Units: kg
arithmetic mean (standard deviation)	69.68 ( 9.88 )	-
BMI
Units: kg/m2
arithmetic mean (standard deviation)	25.31 ( 3.28 )	-

End points

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Reporting group title

Vagitocin 400 IU

Reporting group description

Vagitocin 400 IU vaginal gel

Reporting group title

Placebo

Reporting group description

Placebo vaginal gel

Reporting group title

Vagitocin 400 IU

Reporting group description

Vagitocin 400 IU vaginal gel

Reporting group title

Placebo

Reporting group description

Placebo vaginal gel

Subject analysis set title

Vagitocin 40 IU, baseline 2 (Moderate)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

VVA symptoms that has been self-identified by the subject as being the most bothersome to her at baseline, shift from baseline (mITT population. Main part)

Subject analysis set title

Vagitocin 40 IU, baseline 3 (Severe)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

VVA symptoms that has been self-identified by the subject as being the most bothersome to her at baseline, shift from baseline (mITT population. Main part)

Subject analysis set title

Placebo , baseline 2 (Moderate)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

VVA symptoms that has been self-identified by the subject as being the most bothersome to her at baseline, shift from baseline (mITT population. Main part)

Subject analysis set title

Placebo , baseline 3 (Severe)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

VVA symptoms that has been self-identified by the subject as being the most bothersome to her at baseline, shift from baseline (mITT population. Main part)

Primary: Change from baseline to Week 12 in severity of the VVA symptom that has been self-identified by the subject as being the MBS to her at baseline.

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End point title

Change from baseline to Week 12 in severity of the VVA symptom that has been self-identified by the subject as being the MBS to her at baseline.

End point description

Change from baseline to Week 12 in severity of the VVA symptom that has been self-identified by the subject as being the MBS to her at baseline. Severity was defined as; 0=None, 1 = Mild, 2 = Moderate, 3=Severe

End point type

Primary

End point timeframe

Change from baseline to Week 12

End point values	Vagitocin 400 IU	Placebo	Vagitocin 40 IU, baseline 2 (Moderate)	Vagitocin 40 IU, baseline 3 (Severe)	Placebo , baseline 2 (Moderate)	Placebo , baseline 3 (Severe)
Number of subjects analysed	0 ^[1]	0 ^[2]	31	48	43	35
Units: percentage
number (not applicable)
0=None			14	9	19	6
1=Mild			8	6	17	12
2=Moderate			6	20	4	6
3=Severe			3	13	3	11
Missing			0	0	0	0

Notes
[1] - Endpoint reported on other reporting groups
[2] - Endpoint reported on other reporting groups

Statistical analysis, Main part

Statistical analysis description

A Cochran-Mantel-Haenszel test using modified ridit scores (Wilcoxon rank sum test) adjusted for the baseline value was performed.

Comparison groups

Vagitocin 40 IU, baseline 2 (Moderate) v Vagitocin 40 IU, baseline 3 (Severe) v Placebo , baseline 2 (Moderate) v Placebo , baseline 3 (Severe)

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

< 0.05

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[3] - The study was to be considered successful if the two-sided p-value in the statistical analysis of the primary endpoint for the main study was less than 0.0500 and in favour of the active treatment.

Adverse events

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Timeframe for reporting adverse events

AE reporting from signed informed consent to study completion (Approximately 14 weeks)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.1

Reporting group title

Vagitocin 400 IU, main part

Reporting group description

Vagitocin 400 IU vaginal gel,

Reporting group title

Placebo, main part

Reporting group description

Placebo vaginal gel

Reporting group title

Vagitocin 400 IU, exploratory part

Reporting group description

Reporting group title

Placebo, exploratory part

Reporting group description

Serious adverse events	Vagitocin 400 IU, main part	Placebo, main part	Vagitocin 400 IU, exploratory part	Placebo, exploratory part
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 81 (1.23%)	1 / 80 (1.25%)	0 / 31 (0.00%)	0 / 10 (0.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
subjects affected / exposed	1 / 81 (1.23%)	0 / 80 (0.00%)	0 / 31 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 81 (0.00%)	1 / 80 (1.25%)	0 / 31 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Rib fracture
subjects affected / exposed	0 / 81 (0.00%)	1 / 80 (1.25%)	0 / 31 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Vagitocin 400 IU, main part	Placebo, main part	Vagitocin 400 IU, exploratory part	Placebo, exploratory part
Total subjects affected by non serious adverse events
subjects affected / exposed	20 / 81 (24.69%)	9 / 80 (11.25%)	7 / 31 (22.58%)	6 / 10 (60.00%)
Investigations
Biopsy endometrium normal
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 31 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	1
Reproductive system and breast disorders
Vaginal discharge
subjects affected / exposed	8 / 81 (9.88%)	4 / 80 (5.00%)	2 / 31 (6.45%)	1 / 10 (10.00%)
occurrences all number	8	4	2	1
Vaginal odour
subjects affected / exposed	2 / 81 (2.47%)	2 / 80 (2.50%)	2 / 31 (6.45%)	2 / 10 (20.00%)
occurrences all number	5	2	2	2
Vaginal haemorrhage
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	0 / 31 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	1
Gastrointestinal disorders
Nausea
subjects affected / exposed	1 / 81 (1.23%)	0 / 80 (0.00%)	0 / 31 (0.00%)	1 / 10 (10.00%)
occurrences all number	1	0	0	1
Infections and infestations
Urinary tract infection
subjects affected / exposed	5 / 81 (6.17%)	2 / 80 (2.50%)	1 / 31 (3.23%)	1 / 10 (10.00%)
occurrences all number	6	2	1	1
Influenza
subjects affected / exposed	4 / 81 (4.94%)	1 / 80 (1.25%)	1 / 31 (3.23%)	2 / 10 (20.00%)
occurrences all number	4	1	1	2
Nasopharyngitis
subjects affected / exposed	0 / 81 (0.00%)	0 / 80 (0.00%)	1 / 31 (3.23%)	2 / 10 (20.00%)
occurrences all number	0	0	1	2

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Were there any global substantial amendments to the protocol? Yes

22 Aug 2016

There was one substantial amendment to the clinical study protocol during the study, which resulted in the removal of an inclusion criterion and in the update of the vulvovaginal atrophy (VVA) symptoms self-assessment questionnaire.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Phase 2b, Double-blind, Randomized, Parallel, Placebo-Controlled Study to Evaluate the 12-week Efficacy of Vagitocin in Postmenopausal Women with Symptoms of Vulvovaginal Atrophy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline to Week 12 in severity of the VVA symptom that has been self-identified by the subject as being the MBS to her at baseline.

Primary: Change from baseline to Week 12 in severity of the VVA symptom that has been self-identified by the subject as being the MBS to her at baseline.

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: A Phase 2b, Double-blind, Randomized, Parallel, Placebo-Controlled Study to Evaluate the 12-week Efficacy of Vagitocin in Postmenopausal Women with Symptoms of Vulvovaginal Atrophy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline to Week 12 in severity of the VVA symptom that has been self-identified by the subject as being the MBS to her at baseline.

Primary: Change from baseline to Week 12 in severity of the VVA symptom that has been self-identified by the subject as being the MBS to her at baseline.

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2b, Double-blind, Randomized, Parallel, Placebo-Controlled Study to Evaluate the 12-week Efficacy of Vagitocin in Postmenopausal Women with Symptoms of Vulvovaginal Atrophy