MenopausePhase 3NCT00560833

Dose-Finding Safety and Efficacy Trial of Org50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (46101/P06459/MK-8265-012)

A Phase 3 study testing esmirtazapine in people with Menopause and Vasomotor Symptoms, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 to 65 years, women only
Conditions the study is for: Menopause, Vasomotor Symptoms
What is being tested?: esmirtazapine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 943 participants
Where: No sites listed yet
Study dates: 15 Oct 2004to 15 Jan 2006
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 65 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

postmenopausal women, defined as:
12 months of spontaneous amenorrhea;
OR 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone
(FSH) levels >40 mIU/mL;
OR 6 weeks post surgical bilateral oophorectomy with or without hysterectomy.
In case the menopausal status of a subject was unclear because of a hysterectomy, the serum FSH level had to be >40 mIU/mL. If the date of the last menstruation was not clear because of perimenopausal hormone use, then the subject had to have a serum FSH level >40 mIU/mL after completion of a washout period (see exclusion criteria below); be >= 40 and <= 65 years of age;

Show all 10Show fewer

have a body mass index (BMI) >= 18 and <= 32 kg/m^2;
minimum of 7 moderate to severe hot flushes per day or 50 per week, as quantified from daily diary recordings during at least 7 days preceding randomization to trial medication;
able to handle the electronic diary device after training and having at least 80% compliance on complete daily diary entries during the period prior to randomization;
give voluntary written Informed Consent (IC) after the scope and nature of the investigation had been explained, before screening evaluations.

Who cannot join

history or presence of any malignancy, except non-melanoma skin cancers
any clinically unstable or uncontrolled renal, hepatic, endocrine,
respiratory, hematological, neurological, cardiovascular, or cerebrovascular disease that would put the subject at safety risk or mask measure of efficacy
history of seizures or epilepsy; history or presence of clinically significant depression or other psychiatric disorder which, in the opinion of the investigator, might compromise or confound the participant's participation in the trial; abnormal clinically relevant vaginal bleeding
any clinically relevant (opinion of investigator) abnormal finding during physical, gynecological and breast examination at screening; abnormal, clinically significant results of mammography. Mammography had to have been performed within the last 9 months prior to screening, otherwise it had to be done before inclusion into the trial. For non-US sites, if local laws or guidelines did not allow or advise such frequent mammograms, the documented local laws or guidelines were to be followed; abnormal cervical smear test results (corresponding to Pap III and higher, including Low-Grade Squamous Intraepithelial Lesion (LSIL), High-Grade Squamous Intraepithelial Lesion (HSIL), Cervical Intraepithelial Neoplasia (CIN) 1 and higher). A cervical smear had to have been performed within the last 9 months prior to screening, otherwise it had to be done before inclusion into the trial; hematological or biochemical values at screening outside the reference ranges considered clinically relevant in the opinion of the investigator
high blood pressure (BP) (sitting systolic BP >170 mmHg and/or diastolic BP >100 mmHg)
use of any drug product containing estrogens, progestins, androgens, or tibolone prior to screening (and up to and including randomization) within specified time frames

About this study

Official title: A Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Four Different Doses of Org 50081 in the Treatment of Moderate to Severe Vasomotor Symptoms Associated With the Menopause

The most direct treatment of vasomotor symptions (hot flushes) may be by means of 5-HT2A receptor antagonist. Mirtazapine is a potent blocker of 5-HT2A receptors and was found to be effective in reducing the number and intensity of hot flushes in preliminary trials. Also several Selective Serotonin Reuptake Inhibitors (SSRIs) and other similar compounds have been investigated to manage hot flushes, confirming the role of the serotonergic system. In the present trial, the efficacy and safety of four different doses of esmirtazapine compared to placebo was investigated in women with moderate to severe vasomotor symptoms associated with the menopause. The primary study hypothesis was that esmirtazapine would show superior efficacy to placebo.

Conditions: Menopause, Vasomotor Symptoms
Being tested: esmirtazapine, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

esmirtazapineDrug
Also called Esmirtazapine maleate, SCH 900265, Org 50081
PlaceboDrug

Study groups in NCT00560833
Study group	Role	What they receive
Placebo	Placebo comparator	Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks Receives: Drug: Placebo
Esmirtazapine 2.25 mg	Experimental	Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks Receives: Drug: esmirtazapine
Esmirtazapine 4.5 mg	Experimental	Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks Receives: Drug: esmirtazapine
Esmirtazapine 9 mg	Experimental	Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks Receives: Drug: esmirtazapine
Esmirtazapine 18 mg	Experimental	Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks Receives: Drug: esmirtazapine

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4
Participants recorded the frequency of vasomotor symptoms (hot flushes) on an electronic diary card (LogPad®) on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Measured: Baseline and Week 4
Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 12
Participants recorded the frequency of vasomotor symptoms (hot flushes) on a LogPad on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Measured: Baseline and Week 12
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4
Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Measured: Baseline and Week 4
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12
Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Measured: Baseline and Week 12

Secondary outcomes (1)

Change From Baseline in Vasomotor Symptoms Score Per Women's Health Questionnaire (WHQ) at Week 12
The WHQ is a 36-item, user-friendly, and rapid way of assessing nine domains of physical and emotional health for mid-aged women. Participants self-administered the WHQ questionnaire; scoring is based on a 4-point scale as follows: 'Yes definitely=1', 'Yes sometimes=2', 'No not much=3' and 'No not at all=4'. Each score is transformed to a value '1' for scores '1' and '2' and to a value '0' for scores '3' and '4'. Vasomotor symptoms encompass Items 19 and 27 of the 36 total items. The transformed sums of items 19+27 are divided by 2 to get the score; therefore, the domain ranges from 0 to 1, where lower values are better.
Measured: Baseline and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Oct 200415 Jan 2006

First posted20 Nov 2007 (estimated)
Study start15 Oct 2004
Primary completion15 Jan 2006
Study completion15 Jan 2006

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for MenopauseStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 943 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00560833
Sponsor's protocol ID: P06459
Other IDs: 46101, MK-8265-012, 2004-000469-36, 2004
Status last verified: Mar 2019
First submitted: 16 Nov 2007
Last updated: 2 Apr 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Birkhaeuser M, Bitzer J, Braat S, Ramos Y. Esmirtazapine treatment of postmenopausal vasomotor symptoms: two randomized controlled trials. Climacteric. 2019 Jun;22(3):312-322. doi: 10.1080/13697137.2018.1561664. Epub 2019 Feb 4.
PubMed 30712391

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 2 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Four Different Doses of Org 50081 in the Treatment of Moderate to Severe Vasomotor Symptoms Associated With the Menopause
ClinicalTrials.gov ID: NCT00560833
Acronym / sponsor ID: P06459
Conditions: Menopause, Vasomotor Symptoms
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 943 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 15 Oct 2004 (actual)
Primary completion: 15 Jan 2006 (actual)
Study completion: 15 Jan 2006 (actual)
First posted: 20 Nov 2007 (estimated)
Results: Posted 30 Jun 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboParticipants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks
Esmirtazapine 2.25 mg	Experimental	Drug: esmirtazapineParticipants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks
Esmirtazapine 4.5 mg	Experimental	Drug: esmirtazapineParticipants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks
Esmirtazapine 9 mg	Experimental	Drug: esmirtazapineParticipants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks
Esmirtazapine 18 mg	Experimental	Drug: esmirtazapineParticipants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks

Who may qualify

Ages: 40 to 65 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

postmenopausal women, defined as:
12 months of spontaneous amenorrhea;
OR 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone
(FSH) levels >40 mIU/mL;
OR 6 weeks post surgical bilateral oophorectomy with or without hysterectomy.

Key exclusion criteria (7 listed)

history or presence of any malignancy, except non-melanoma skin cancers
any clinically unstable or uncontrolled renal, hepatic, endocrine,
respiratory, hematological, neurological, cardiovascular, or cerebrovascular disease that would put the subject at safety risk or mask measure of efficacy
history of seizures or epilepsy; history or presence of clinically significant depression or other psychiatric disorder which, in the opinion of the investigator, might compromise or confound the participant's participation in the trial; abnormal clinically relevant vaginal bleeding
any clinically relevant (opinion of investigator) abnormal finding during physical, gynecological and breast examination at screening; abnormal, clinically significant results of mammography. Mammography had to have been performed within the last 9 months prior to screening, otherwise it had to be done before inclusion into the trial. For non-US sites, if local laws or guidelines did not allow or advise such frequent mammograms, the documented local laws or guidelines were to be followed; abnormal cervical smear test results (corresponding to Pap III and higher, including Low-Grade Squamous Intraepithelial Lesion (LSIL), High-Grade Squamous Intraepithelial Lesion (HSIL), Cervical Intraepithelial Neoplasia (CIN) 1 and higher). A cervical smear had to have been performed within the last 9 months prior to screening, otherwise it had to be done before inclusion into the trial; hematological or biochemical values at screening outside the reference ranges considered clinically relevant in the opinion of the investigator

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
esmirtazapineAlso: Esmirtazapine maleate, SCH 900265, Org 50081	Drug	Esmirtazapine 18 mg, Esmirtazapine 2.25 mg, Esmirtazapine 4.5 mg, Esmirtazapine 9 mg
Placebo	Drug	Placebo

Primary outcome

Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4
Time frame: Baseline and Week 4
Participants recorded the frequency of vasomotor symptoms (hot flushes) on an electronic diary card (LogPad®) on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 12
Time frame: Baseline and Week 12
Participants recorded the frequency of vasomotor symptoms (hot flushes) on a LogPad on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4
Time frame: Baseline and Week 4
Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12
Time frame: Baseline and Week 12
Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

1 secondary outcome

Change From Baseline in Vasomotor Symptoms Score Per Women's Health Questionnaire (WHQ) at Week 12
Time frame: Baseline and Week 12

Results and safety

Results posted to the registry on 30 Jun 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	317	273
Esmirtazapine 2.25 mg	155	129
Esmirtazapine 4.5 mg	160	121
Esmirtazapine 9 mg	155	124
Esmirtazapine 18mg	156	114

Primary outcome: Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4

Time frame: Baseline and Week 4. Mean (Standard Deviation). Unit: Number of events

Measure	Placebo n = 294	Esmirtazapine 2.25 mg n = 138	Esmirtazapine 4.5 mg n = 139	Esmirtazapine 9 mg n = 137	Esmirtazapine 18mg n = 138
Value	-3.9 (4.2)	-5.6 (3.8)	-6.0 (3.6)	-6.0 (4.0)	-6.0 (4.4)

Placebo vs Esmirtazapine 2.25 mg: Mean Difference (Final Values): -1.4 (95% CI -2.3 to -0.4), p <0.01, ANCOVA
Placebo vs Esmirtazapine 4.5 mg: Mean Difference (Final Values): -2.2 (95% CI -3.1 to -1.2), p <0.01, ANCOVA
Placebo vs Esmirtazapine 9 mg: Mean Difference (Final Values): -1.9 (95% CI -2.9 to -1.0), p <0.01, ANCOVA

Population analysed: The intent-to-treat (ITT) population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.

Primary outcome: Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 12

Time frame: Baseline and Week 12. Mean (Standard Deviation). Unit: number of events

Measure	Placebo n = 294	Esmirtazapine 2.25 mg n = 138	Esmirtazapine 4.5 mg n = 139	Esmirtazapine 9 mg n = 137	Esmirtazapine 18mg n = 138
Value	-4.9 (4.8)	-6.2 (5.1)	-6.7 (3.9)	-6.9 (4.4)	-6.5 (4.4)

Placebo vs Esmirtazapine 2.25 mg: Mean Difference (Final Values): -1.0 (95% CI -2.0 to 0.0), p = 0.06, ANCOVA
Placebo vs Esmirtazapine 4.5 mg: Mean Difference (Final Values): -2.0 (95% CI -3.0 to -0.9), p <0.01, ANCOVA
Placebo vs Esmirtazapine 9 mg: Mean Difference (Final Values): -1.9 (95% CI -2.9 to -0.9), p <0.01, ANCOVA

Population analysed: The ITT population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.

Primary outcome: Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4

Time frame: Baseline and Week 4. Mean (Standard Deviation). Unit: score on a scale

Measure	Placebo n = 294	Esmirtazapine 2.25 mg n = 138	Esmirtazapine 4.5 mg n = 139	Esmirtazapine 9 mg n = 137	Esmirtazapine 18mg n = 138
Value	-0.09 (0.23)	-0.11 (0.22)	-0.15 (0.25)	-0.16 (0.24)	-0.15 (0.24)

Placebo vs Esmirtazapine 2.25 mg: Mean Difference (Final Values): -0.03 (95% CI -0.09 to 0.03), p = 0.62, ANCOVA
Placebo vs Esmirtazapine 4.5 mg: Mean Difference (Final Values): -0.06 (95% CI -0.12 to -0.01), p = 0.02, ANCOVA
Placebo vs Esmirtazapine 9 mg: Mean Difference (Final Values): -0.07 (95% CI -0.13 to -0.01), p = 0.01, ANCOVA

Population analysed: The ITT population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.

Primary outcome: Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12

Time frame: Baseline and Week 12. Mean (Standard Deviation). Unit: score on a scale

Measure	Placebo n = 294	Esmirtazapine 2.25 mg n = 138	Esmirtazapine 4.5 mg n = 139	Esmirtazapine 9 mg n = 137	Esmirtazapine 18mg n = 138
Value	-0.12 (0.28)	-0.10 (0.27)	-0.15 (0.29)	-0.18 (0.26)	-0.17 (0.26)

Placebo vs Esmirtazapine 2.25 mg: Mean Difference (Final Values): 0.01 (95% CI -0.06 to 0.07), p = 1.0, ANCOVA
Placebo vs Esmirtazapine 4.5 mg: Mean Difference (Final Values): -0.03 (95% CI -0.09 to 0.04), p = 0.72, ANCOVA
Placebo vs Esmirtazapine 9 mg: Mean Difference (Final Values): -0.06 (95% CI -0.12 to 0.01), p = 0.13, ANCOVA

Population analysed: The ITT population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	2 of 317 (0.6%)	128 of 317 (40.4%)	Not reported
Esmirtazapine 2.25 mg	1 of 154 (0.6%)	93 of 154 (60.4%)	Not reported
Esmirtazapine 4.5 mg	3 of 160 (1.9%)	99 of 160 (61.9%)	Not reported
Esmirtazapine 9 mg	2 of 155 (1.3%)	102 of 155 (65.8%)	Not reported
Esmirtazapine 18mg	0 of 155 (0%)	123 of 155 (79.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 30712391Birkhaeuser M, Bitzer J, Braat S, Ramos Y. Esmirtazapine treatment of postmenopausal vasomotor symptoms: two randomized controlled trials. Climacteric. 2019 Jun;22(3):312-322. doi: 10.1080/13697137.2018.1561664. Epub 2019 Feb 4.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing esmirtazapine in people with Menopause and Vasomotor Symptoms, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4 (time frame: Baseline and Week 4). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00560833, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2019.