Neuropeptide Treatment for Hot Flushes During the Menopause

NCT02668185 | Completed Phase 2 Results DMC

• 1 other identifier: 15HH2867
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Menopausal Flushing

Keywords

Menopausal flushing

Outcome Measures

Primary Outcomes (1)

• 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.

  Final week of each 4 week treatment period

Secondary Outcomes (4)

• Hot Flush Severity

  Twice daily, morning and night for 14 weeks

• Hot Flush Bother

  twice daily (day/night) for 14 weeks

• Hot Flush Interference

  Daily at bedtime for 14 weeks

• Skin Conductance Monitor Data.

  Once per week for 48 hours over 14 weeks

Study Arms (2)

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

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

Drug: Placebo

Interventions

NK3R antagonist - AZD4901 DRUG

Neurokinin 3 receptor antagonist

Also known as: nil others

Active drug first

Placebo DRUG

Placebo

Also known as: nil others

Placebo

Eligibility Criteria

• Age: 40 Years - 62 Years
• Gender Eligibility Details: 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.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• Confirmed history of ischaemic heart disease.
• Past (within 1 year of enrollment) or present alcohol or substance abuse
• 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)

Sponsors & Collaborators

• Imperial College London: lead
• Medical Research Council: collaborator
• AstraZeneca: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

NIHR/Wellcome Trust Imperial CRF

London, W12 0HS, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 32318647 DERIVED

• 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.

  PMID: 29533369 DERIVED

• 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.

  PMID: 28385352 DERIVED

MeSH Terms

Conditions

Hot Flashes

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Professor Wajit Dhillo
• Organization: Imperial College London

w.dhillo@imperial.ac.uk

+44 (0)20 7594 2489

Study Officials

• Waljit S Dhillo, MBBS PhD

  Imperial College and NHS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: January 29, 2016
• Study Start: February 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: May 3, 2021
• Results First Posted: May 3, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)