Menopausal FlushingPhase 2NK3RNCT02668185

Neuropeptide Treatment for Hot Flushes During the Menopause

A Phase 2 study testing NK3R antagonist - AZD4901 in people with Menopausal Flushing, run by Imperial College London at 1 site in United Kingdom.

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

Placebo-controlled, double-blinded, cross-over clinical trial of a new investigational product Read more about this study

Who is it for?: Ages 40 to 62 years, women onlyHealthy volunteers can take part
Conditions the study is for: Menopausal Flushing
What is being tested?: NK3R antagonist - AZD4901
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 37 participants
Where: 1 siteUnited Kingdom
Study dates: 1 Feb 2016to 1 Jan 2017
Phase: Phase 2
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 62 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Menopausal women (≥12 months since last menstrual period or bilateral oophorectomy or with a follicle stimulating hormone (FSH) level ≥20 milli-international units/millilitre (mIU/mL) and an estradiol level <190pmol/l in the absence of a reliable menstrual marker (hysterectomy with ovarian preservation or endometrial ablation)) aged 40-62 years with >7 hot flushes/day some of which are reported as severe or bothersome who have not been on treatment for menopausal symptoms for the preceding 8 weeks.

Who cannot join

Significant illness, as judged by the Investigator, within 2 weeks of first study visit.
Volunteer has clinical, laboratory, or electrocardiogram (ECG) evidence of uncontrolled hypertension (defined as systolic blood pressure of ≥ 160 mmHg and/or diastolic blood pressure of ≥100 mmHg); uncontrolled diabetes; or significant pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator.
Participant has a history of Gilbert's syndrome, infectious hepatitis, or other significant hepatic disease (e.g. chronic hepatitis, cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis, non-alcoholic steatohepatitis, or hereditary liver disease) in the opinion of the Investigator.
Participant has a history of surgery which in the opinion of the investigator could cause malabsorption (e.g. gastric or small intestinal surgery or gastric bypass surgery or banding), or patient has a disease that causes malabsorption.
Clinically significant abnormal ECG and/or abnormalities in ECG at screening as judged by the Investigator.
A marked prolongation of QT/corrected QT (QTc) interval (e.g. repeated demonstration of a QTc interval > 450 ms).

Show all 24Show fewer

Confirmed history of ischaemic heart disease.
Past (within 1 year of enrollment) or present alcohol or substance abuse
Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 3 months of the first administration of AZD4901 in this study. The period of exclusion begins 3 months after the final dose. (Note: patients consented and screened, but not randomised in a previous study are not excluded.)
Participant has a history of neoplastic disease within 5 years prior to signing informed consent or is currently on ongoing treatment to prevent cancer recurrence.
Involvement in the planning and/or conduct of the study (applies to any AstraZeneca employee and their close relatives and/or staff at the study site directly involved in the study, regardless of their role in accordance with their internal procedures)
Inability to understand or cooperate with the requirements of the study
Participant is legally or mentally incapacitated
Participant has significant psychiatric disease or treatment for psychiatric disease e.g. selective serotonin re-uptake inhibitors (SSRIs) which in the opinion of the Investigator may influence the results of the study.
Participant has abnormal screening laboratory values as per the guidelines listed below or other clinically significant, unexplained laboratory abnormality according to the Investigator:
Aspartate aminotransferase (AST) >1.5 times upper limit of normal (ULN)
Alanine aminotransferase (ALT) > 1.5 times ULN
Total bilirubin >1.5 times ULN
Serum creatinine >2.0 times ULN
Clinically relevant disease and abnormalities (past or present), which in the opinion of the Investigator, may either put the patient at risk to participate in this study or may influence the results of the study or the patient's ability to participate in the study.
Participant has a history of hyperthyroidism or hypothyroidism or abnormal screening thyroid tests, as judged by the Investigator. Patients with hypothyroidism who are stable on treatment with normal thyroid function tests may be included in the study if in the opinion of the Investigator this will not influence the results of the study.
Participant has seizures, patients with history of seizures or with conditions that increase the risk of seizures.
Participant has a history of hypersensitivity to more than 2 chemical classes of drugs, including prescription and over-the-counter medications.
Participant has taken any potent or moderate CYP3A4 or CYP2C9 inhibitors, potent or moderate CYP3A4 or CYP2C9 inducers, hormonal contraceptives, antiandrogenic drugs, or other medications specified for the time frame

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

NIHR/Wellcome Trust Imperial CRF
London, W12 0HS

Other trials in United Kingdom

About this study

Official title: Neurokinin 3 Receptor Antagonism as a Novel Treatment for Menopausal Hot Flushes

Placebo-controlled, double-blinded, cross-over clinical trial of a new investigational product

Read the detailed description

Double-blinded, placebo-controlled, 2-way crossover study in 30 menopausal women with untreated hot flushes treated with a neurokinin 3 receptor (NK3R) antagonist

Aims:

To investigate whether an NK3R antagonist can reduce menopausal flushing

Treatment:

4 weeks administration of active drug and placebo in random order

Conditions: Menopausal Flushing
Being tested: NK3R antagonist - AZD4901, Placebo
Keywords: Menopausal flushing
Medical subject headings: Hot Flashes

What participants receive

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

NK3R antagonist - AZD4901Drug
Also called nil others
Neurokinin 3 receptor antagonist
PlaceboDrug
Also called nil others
Placebo

Study groups in NCT02668185
Study group	Role	What they receive
Active drug first	Experimental	Baseline period - 2 weeks NK3R antagonist - AZD4901 - 40mg bd - 4 weeks Washout period - 2 weeks Matched placebo orally bd - 2 weeks Monitoring period - 2 weeks Receives: Drug: NK3R antagonist - AZD4901
Placebo	Placebo comparator	Baseline period - 2 weeks Matched placebo orally bd - 2 weeks Washout period - 2 weeks NK3R antagonist - AZD4901 - 40mg bd - 4 weeks Monitoring period - 2 weeks Receives: Drug: Placebo

What is being measured

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

Total Number of Hot Flushes During the Final Week of Each 4 Weeks Treatment Period
To ensure accurate records, participants recorded their flushes in real time using either a tally chart on a piece of paper (n=34) or an application on their smartphone such as Tally Counter (Pixel Research Labs, Minneapolis-Saint Paul, MN, USA; n=3), and then collated their total number of flushes twice daily on waking to record previous overnight symptoms and before bed to record daytime symptoms.
Measured: Final week of each 4 week treatment period

Secondary outcomes (4)

Hot Flush Severity
Score on a scale - HF severity (rated as 1-nil, 2-mild, 3-moderate, 4-severe, as per Joffe 2014) recorded twice daily (day/night as described above for HF frequency). Scores are summed.
Measured: Twice daily, morning and night for 14 weeks
Hot Flush Bother
Score on a scale - HF bother (rated as 1-none, 2-a little, 3-moderate, 4-a lot, as per Joffe 2014) will be recorded twice daily (day/night as described above for HF frequency). The data will be analysed as detailed above for the HF frequency. Scores are summed.
Measured: twice daily (day/night) for 14 weeks
Hot Flush Interference
Score on a scale Menopause Specific Quality of Life (MENQOL) questionnaire 0=not bothered at all - 6=extremely bothered. 4 domains, mean calculated for set of questions in each domain. Overall score is a mean of the means. Highr scor = higher interference.
Measured: Daily at bedtime for 14 weeks
Skin Conductance Monitor Data.
Mean number of flushes detected during the 48 hours by the skin conductance monitoring will be compared each week when the patients receive AZD4901 versus placebo
Measured: Once per week for 48 hours over 14 weeks

Timeline

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

1 Feb 20161 Jan 2017

First posted29 Jan 2016 (estimated)
Study start1 Feb 2016
Primary completion1 Jan 2017
Study completion1 Jan 2017

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 (3)Papers the sponsor has linked to this study.
Other trials for Menopausal FlushingStudies of the same condition, open and under way.
More trials run by Imperial College LondonThe 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02668185
Sponsor's protocol ID: 15HH2867
Acronym: NK3R
Status last verified: Apr 2021
First submitted: 26 Jan 2016
Last updated: 3 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Prague JK, Abbara A, Comninos AN, Jayasena CN, Higham CE, Adaway J, Keevil BG, Veldhuis JD, Dhillo WS. Neurokinin 3 Receptor Antagonists Do Not Increase FSH or Estradiol Secretion in Menopausal Women. J Endocr Soc. 2019 Nov 14;4(2):bvz009. doi: 10.1210/jendso/bvz009. eCollection 2020 Feb 1.
PubMed 32318647
Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Mohideen P, Lin VH, Stern TP, Panay N, Hunter MS, Webber LC, Dhillo WS. Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action. Menopause. 2018 Aug;25(8):862-869. doi: 10.1097/GME.0000000000001090.
PubMed 29533369
Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Nash Z, Doyle C, Papadopoulou DA, Bloom SR, Mohideen P, Panay N, Hunter MS, Veldhuis JD, Webber LC, Huson L, Dhillo WS. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May 6;389(10081):1809-1820. doi: 10.1016/S0140-6736(17)30823-1. Epub 2017 Apr 3.
PubMed 28385352

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?

See locations

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RecruitingPhase 3
A Study to Confirm if Fezolinetant Helps to Reduce Hot Flashes in Indian Women Going Through Menopause
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A Clinical Trial to Evaluate the Effects of A Supplement on Symptoms of Menopause and Overall Well-being
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Active, not recruitingPhase 2
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All Menopausal Flushing trials

Study at a glance

From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Neurokinin 3 Receptor Antagonism as a Novel Treatment for Menopausal Hot Flushes
ClinicalTrials.gov ID: NCT02668185
Acronym / sponsor ID: NK3R / 15HH2867
Conditions: Menopausal Flushing
Keywords: Menopausal flushing
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: Imperial College LondonUniversity, hospital or other
Collaborators: Medical Research Council, AstraZeneca, National Institute for Health Research, United Kingdom
Study start: 1 Feb 2016 (actual)
Primary completion: 1 Jan 2017 (actual)
Study completion: 1 Jan 2017 (actual)
First posted: 29 Jan 2016 (estimated)
Results: Posted 3 May 2021

Clinical summary

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

Placebo-controlled, double-blinded, cross-over clinical trial of a new investigational product

Detailed description

Double-blinded, placebo-controlled, 2-way crossover study in 30 menopausal women with untreated hot flushes treated with a neurokinin 3 receptor (NK3R) antagonist

Aims:

To investigate whether an NK3R antagonist can reduce menopausal flushing

Treatment:

4 weeks administration of active drug and placebo in random order

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Active drug first	Experimental	Drug: NK3R antagonist - AZD4901Baseline period - 2 weeks NK3R antagonist - AZD4901 - 40mg bd - 4 weeks Washout period - 2 weeks Matched placebo orally bd - 2 weeks Monitoring period - 2 weeks
Placebo	Placebo comparator	Drug: PlaceboBaseline period - 2 weeks Matched placebo orally bd - 2 weeks Washout period - 2 weeks NK3R antagonist - AZD4901 - 40mg bd - 4 weeks Monitoring period - 2 weeks

Who may qualify

Ages: 40 to 62 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

Menopausal women (≥12 months since last menstrual period or bilateral oophorectomy or with a follicle stimulating hormone (FSH) level ≥20 milli-international units/millilitre (mIU/mL) and an estradiol level <190pmol/l in the absence of a reliable menstrual marker (hysterectomy with ovarian preservation or endometrial ablation)) aged 40-62 years with >7 hot flushes/day some of which are reported as severe or bothersome who have not been on treatment for menopausal symptoms for the preceding 8 weeks.

Key exclusion criteria (24 listed)

Significant illness, as judged by the Investigator, within 2 weeks of first study visit.
Volunteer has clinical, laboratory, or electrocardiogram (ECG) evidence of uncontrolled hypertension (defined as systolic blood pressure of ≥ 160 mmHg and/or diastolic blood pressure of ≥100 mmHg); uncontrolled diabetes; or significant pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator.
Participant has a history of Gilbert's syndrome, infectious hepatitis, or other significant hepatic disease (e.g. chronic hepatitis, cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis, non-alcoholic steatohepatitis, or hereditary liver disease) in the opinion of the Investigator.
Participant has a history of surgery which in the opinion of the investigator could cause malabsorption (e.g. gastric or small intestinal surgery or gastric bypass surgery or banding), or patient has a disease that causes malabsorption.
Clinically significant abnormal ECG and/or abnormalities in ECG at screening as judged by 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
NK3R antagonist - AZD4901Also: nil othersNeurokinin 3 receptor antagonist	Drug	Active drug first
PlaceboAlso: nil othersPlacebo	Drug	Placebo

Primary outcome

Total Number of Hot Flushes During the Final Week of Each 4 Weeks Treatment Period
Time frame: Final week of each 4 week treatment period
To ensure accurate records, participants recorded their flushes in real time using either a tally chart on a piece of paper (n=34) or an application on their smartphone such as Tally Counter (Pixel Research Labs, Minneapolis-Saint Paul, MN, USA; n=3), and then collated their total number of flushes twice daily on waking to record previous overnight symptoms and before bed to record daytime symptoms.

4 secondary outcomes

Hot Flush Severity
Time frame: Twice daily, morning and night for 14 weeks
Hot Flush Bother
Time frame: twice daily (day/night) for 14 weeks
Hot Flush Interference
Time frame: Daily at bedtime for 14 weeks
Skin Conductance Monitor Data.
Time frame: Once per week for 48 hours over 14 weeks

Results and safety

Results posted to the registry on 3 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active Drug First Then Placebo	20	20
Placebo First Then Active Drug	17	17

Primary outcome: Total Number of Hot Flushes During the Final Week of Each 4 Weeks Treatment Period

Time frame: Final week of each 4 week treatment period. Mean (95% Confidence Interval). Unit: hot flushes

Measure	Active Drug n = 28	Placebo n = 28
Value	19.35 (15.99 to 23.42)	49.01 (40.81 to 58.56)

Active Drug vs Placebo: Mean Difference (Net): 29.66 (95% CI 17.39 to 42.87), p <0.0001, generalised linear mixed model with a Po

Population analysed: Whole group intention to treat analysis irrespective of treatment assignment order, adjusted means from crossover analysis with 95% CIs: percentage change in total no. hot flush frequency during final week of 4 week treatment period with MLE4901 and placebo vs with total no. hot flush frequency during the final week of the 2 week baseline period.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 10 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Active Drug First Then Placebo	0 of 28 (0%)	3 of 28 (10.7%)	0 of 28
Placebo First Then Active Drug	0 of 28 (0%)	0 of 28 (0%)	0 of 28

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32318647Prague JK, Abbara A, Comninos AN, Jayasena CN, Higham CE, Adaway J, Keevil BG, Veldhuis JD, Dhillo WS. Neurokinin 3 Receptor Antagonists Do Not Increase FSH or Estradiol Secretion in Menopausal Women. J Endocr Soc. 2019 Nov 14;4(2):bvz009. doi: 10.1210/jendso/bvz009. eCollection 2020 Feb 1.
Derived from this study: PubMed 29533369Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Mohideen P, Lin VH, Stern TP, Panay N, Hunter MS, Webber LC, Dhillo WS. Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action. Menopause. 2018 Aug;25(8):862-869. doi: 10.1097/GME.0000000000001090.
Derived from this study: PubMed 28385352Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Nash Z, Doyle C, Papadopoulou DA, Bloom SR, Mohideen P, Panay N, Hunter MS, Veldhuis JD, Webber LC, Huson L, Dhillo WS. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May 6;389(10081):1809-1820. doi: 10.1016/S0140-6736(17)30823-1. Epub 2017 Apr 3.
Individual participant dataSharing planned: No

Related trials for Menopausal Flushing

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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.

Waljit S Dhillo, MBBS PhD principal investigator

Imperial College and NHS Trust

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NK3R antagonist - AZD4901 in people with Menopausal Flushing, run by Imperial College London at 1 site in United Kingdom.

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 1 inclusion and 24 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 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 3 May 2021). 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?

Total Number of Hot Flushes During the Final Week of Each 4 Weeks Treatment Period (time frame: Final week of each 4 week treatment period). 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 NCT02668185, which also lists 3 linked publications.

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 3 May 2021.