Neuropeptide Treatment for Hot Flushes During the Menopause
Condition: Menopausal Flushing
MeSH terms: Flushing; Hot Flashes
Intervention: NK3R antagonist - AZD4901; Placebo
Intervention description: Neurokinin 3 receptor antagonist; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 37.0
Sex: Female
Minimum age: 40 Years
Maximum age: 62 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Menopausal flushing

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

Eligibility 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