E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Hot flushes during the menopause |
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E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027311 |
E.1.2 | Term | Menopause flushing |
E.1.2 | System Organ Class | 100000004872 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate if AZD4901 is effective in reducing the frequency of menopausal hot flushes by mean Hot Flush (HF) frequency per day (HF/day). |
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E.2.2 | Secondary objectives of the trial |
average mean HF frequency
HF severity
HF bother
HF interference
A general menopausal symptom scale score (MENQOL questionnaire, Hilditch 1996) will be recorded daily on waking
Skin conductance monitor data.
Modified Medication Adherence Questionnaire to assess compliance (Morisky 1986) will be recorded twice daily.
Gonadotrophins & Oestradiol. Blood will be taken at each weekly visit throughout entire study period to measure gonadotrophins & Oestradiol.
Mean LH ±FSH during 8h blood sampling studies. These visits will be voluntary and subject to patient’s consent and availability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Menopausal women (≥12 months since last menstrual period or bilateral oophorectomy or with an FSH level ≥20 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 >7HF/day some of which are reported as severe or bothersome who have not been on treatment for menopausal symptoms for the preceding 8 weeks. |
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E.4 | Principal exclusion criteria |
1.Significant illness, as judged by the Investigator, within 2 weeks of first study visit.
2.Volunteer has clinical, laboratory, or 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.Patient 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.Patient 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/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 enrolment) 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.Patient 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.Patient is legally or mentally incapacitated
14.Patient has significant psychiatric disease or treatment for psychiatric disease e.g. SSRI’s which in the opinion of the Investigator may influence the results of the study.
15.Patient 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 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.Patient 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. Patient has a history of hypersensitivity to more than 2 chemical classes of drugs, including prescription and over-the-counter medications.
19.Patient has taken any potent or moderate CYP3A4 or CYP2C9 inhibitors, potent or moderate CYP3A4 or CYP2C9 inducers, hormonal contraceptives, antiandrogenic drugs, or other medications for the time frame specified in Table 1 in the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean HF frequency per day (HF/day). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
average mean HF frequency
HF severity
HF bother
HF interference
A general menopausal symptom scale score (MENQOL questionnaire, Hilditch 1996) will be recorded daily on waking
Skin conductance monitor data.
Modified Medication Adherence Questionnaire to assess compliance (Morisky 1986) will be recorded twice daily.
Gonadotrophins & Oestradiol. Blood will be taken at each weekly visit throughout entire study period to measure gonadotrophins & Oestradiol.
Mean LH ±FSH during 8h blood sampling studies. These visits will be voluntary and subject to patient’s consent and availability |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |