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Neuropeptide Treatment for Hot Flushes During the Menopause (NK3R)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Medical Research Council
AstraZeneca
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT02668185
First received: January 26, 2016
Last updated: March 27, 2017
Last verified: March 2017
  Purpose
Placebo-controlled, double-blinded, cross-over clinical trial of a new investigational product

Condition Intervention Phase
Menopausal Flushing
Drug: NK3R antagonist - AZD4901
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: Neurokinin 3 Receptor Antagonism as a Novel Treatment for Menopausal Hot Flushes

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Mean hot flush (HF) frequency [ Time Frame: 4 weeks ]
    Mean HF frequency (HF/day) per participant during the 4th week of a 4-week treatment period with placebo or AZD4901


Secondary Outcome Measures:
  • Mean hot flush (HF) frequency [ Time Frame: 1 week ]
    average mean HF frequency (HF/day) during the 1st week of a 4-week treatment period (days 1-7) will be compared when the patients receive AZD4901 versus placebo and also compared to the average HF frequency data during the 2nd week of the baseline period

  • Mean hot flush frequency [ Time Frame: 5 weeks ]
    average mean HF frequency (HF/day) during the 2nd week of a 4-week treatment period (days 8-14) will be compared when the patients receive AZD4901 versus placebo and also compared to the average HF frequency data during the 2nd week of the baseline period

  • Mean hot flush frequency [ Time Frame: 6 weeks ]
    average mean HF frequency (HF/day) during the 3rd week of a 4-week treatment period (days 15-21) will be compared when the patients receive AZD4901 versus placebo and also compared to the average HF frequency data during the 2nd week of the baseline period

  • Hot flush severity [ Time Frame: 14 weeks ]
    HF severity (rated as 1-nil, 2-mild, 3-moderate, 4-severe, 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

  • Hot flush bother [ Time Frame: 14 weeks ]
    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.

  • Hot flush interference [ Time Frame: 14 weeks ]
    HF interference (Hot Flash Related Daily Interference Scale, as per Carpenter 2001) will be recorded daily at bedtime. The data will be analysed as detailed above for the HF frequency.

  • Gonadotrophins & Oestradiol. [ Time Frame: 14 weeks ]
    Blood will be taken at each weekly visit throughout entire study period to measure gonadotrophins & Oestradiol.

  • Skin conductance monitor data. [ Time Frame: 14 weeks ]
    This will be measured for 48 hours non-invasively using a monitor placed on the sternal skin surface following each weekly visit. 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 and also compared to the skin conductance monitor data during the 2nd week of the baseline period


Estimated Enrollment: 30
Actual Study Start Date: February 2016
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active drug
NK3R antagonist - AZD4901 - 40mg bd - for 4 weeks
Drug: NK3R antagonist - AZD4901
Neurokinin 3 receptor antagonist
Other Name: nil others
Placebo Comparator: Placebo
Placebo - 40mg bd - for 4 weeks
Drug: Placebo
Placebo
Other Name: nil others

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

  Eligibility

Ages Eligible for Study:   40 Years to 62 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  1. Significant illness, as judged by the Investigator, within 2 weeks of first study visit.
  2. 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.
  3. 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.
  4. 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.
  5. Clinically significant abnormal ECG and/or abnormalities in ECG at screening as judged by the Investigator.
  6. A marked prolongation of QT/corrected QT (QTc) interval (e.g. repeated demonstration of a QTc interval > 450 ms).
  7. Confirmed history of ischaemic heart disease.
  8. Past (within 1 year of enrollment) or present alcohol or substance abuse
  9. 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.)
  10. 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.
  11. 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)
  12. Inability to understand or cooperate with the requirements of the study
  13. Participant is legally or mentally incapacitated
  14. 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.
  15. 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
  16. 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.
  17. 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.
  18. Participant has seizures, patients with history of seizures or with conditions that increase the risk of seizures.
  19. Participant has a history of hypersensitivity to more than 2 chemical classes of drugs, including prescription and over-the-counter medications.
  20. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02668185

Locations
United Kingdom
NIHR/Wellcome Trust Imperial CRF
London, United Kingdom, W12 0HS
Sponsors and Collaborators
Imperial College London
Medical Research Council
AstraZeneca
National Institute for Health Research, United Kingdom
Investigators
Principal Investigator: Waljit S Dhillo, MBBS PhD Imperial College and NHS Trust
  More Information

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT02668185     History of Changes
Other Study ID Numbers: 15HH2867
Study First Received: January 26, 2016
Last Updated: March 27, 2017
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Flushing
Hot Flashes
Signs and Symptoms

ClinicalTrials.gov processed this record on April 21, 2017