E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Endometrial glucocorticoid deficiency in Heavy Menstrual Bleeding |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027313 |
E.1.2 | Term | Menorrhagia |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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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 |
Work-up studies (Studies 1&2) To gather preliminary safety and efficacy data from first-in-Heavy Menstrual Bleeding use of oral dexamethasone, in women suffering from objectively verified Heavy Menstrual Bleeding (HMB) Adaptive RCT(Study 3): To identify the optimal dose of oral dexamethasone (Dex) for reduction of Heavy Menstrual Bleeding in women with objectively verified HMB |
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E.2.2 | Secondary objectives of the trial |
Work-up studies (1&2) - the secondary objectives are: 1. To collect information to enable development of the adaptive RCT design 2. To assess effect of Dexamethasone on co-occurring period pain 3. To explore differences in effect of Dexamethasone in those with MBL of 50-80mls, and for those with MBL >80mls 4. To relate diary assessment of treatment effect against measured MBL. 5. To explore whether Dexamethasone has a carry-over effect. In Workup study 1 only a. To establish whether endometrial biopsy is an indicator of MBL change and of Dexamethasone treatment effect b. To examine changes in blood flow in the womb lining before and after taking Dexamethasone c. To assess predictive value of MRI for endometrial biopsy findings and MBL d. To examine whether an assay can be developed for Dexamethasone concentration in endometrial biopsy Adaptive RCT The secondary objectives are: 1. To gather safety data for Dexamethasone in women with objectively verified |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Women will be invited to participate if they fulfil the following criteria: 1. with complaint of HMB, including women with fibroids 2. pre-menopausal 3. age 18 years and over 4. describing menstrual cycles every 21- 42 days 5. If of childbearing potential either agrees to practice a non-hormonal method of contraception for duration of study or has a partner with a vasectomy 6. Workup studies (1&2) – MBL for a single screening period is >= 50mL RCT (study 3) – average MBL for two screening menstrual collections is >= 50mL |
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E.4 | Principal exclusion criteria |
Main exclusion criteria are: 1. A history or current uterus, cervix, ovarian or breast reproductive tract cancer 2. A known severe coagulation disorder 3. Glucocorticoid treatment or sex steroid administration by any route in previous 1 month 4. Thyroid, renal or liver dysfunction 5. Diabetes mellitus 6. Treated moderate/severe hypertension 7. Women with rare hereditary galactose intolerance, lactase deficiency or glucose galactose malabsorption (due to Lactose content of trial medication). 8. A problem with alcohol or drug abuse 9. A mental condition rendering the participant unable to understand the nature and scope of the study 10.Psychotic depressive illness 11.The subject is currently enrolled in an investigational drug or device study or participated in such a study within the previous 30 days and is still in exclusion period 12. Participation in treatment phase in any earlier DexFEM study (1 or 2). 13. The subject has been taking prohibited medication as detailed in protocol section 6.7.3 14. Currently breastfeeding 15. For workup study 1 there will be an additional exclusion criterion of any contra-indication to MRI (eg claustrophobic feelings. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Workup Study 1: (Mechanistic) Change in mean Menstrual Blood Loss between baseline and Dexamethasone treatment cycles Workup Study 2: Difference in mean Meanstrual Blood Loss between placebo and Dexamethasone treatment cycles Adaptive trial: Change in mean MBL between baseline and cycles during randomised (Dexamethasone/placebo) treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Workup study 1- Individual MBL will be assessed for each patient, by laboratory assay, within one to two weeks of her 2nd treatment cycle with Dexamethasone. End point (mean MBL) will be evaluated once data for all 6 participants is complete. Workup study 2 (as for workup study 1) - End point (mean MBL) will be evaluated once data for all 14 participants is complete. Adaptive trial (as for workup study 1) - Overall Endpoint will be evaluated at regular intervals once data are available for sufficient numbers to determine which of the doses studied is optimal to take forward for further study. |
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E.5.2 | Secondary end point(s) |
Workup studies 1 & 2: 1. Menstrual diary score for volume of menstrual period 2. Satisfaction with treatment 3. Unacceptable side-effects 4. Period pain Mechanistic Workup study 1 only; 5. Assessment of the endometrial response to administration of Dexamethasone in a treated and untreated cycle (histological, molecular, and biochemical assays of tissue) Adaptive trial: 1. Menstrual diary score for volume of menstrual period 2. Satisfaction with treatment 3. Unacceptable side-effects 4. Period pain |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Workup studies 1&2 and Adaptive trial:- Individual End points will be evaluated once data are complete for each study participant ie approx 2-3 weeks after last study visit. Unacceptable side effects will be evaluated for each participant at regular intervals during each treatment cycle. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Study 3 will use adaptive randomisation |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Yes |
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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LVLSLast post treatment review visit of last subject in adaptive 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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |