E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Premenstrual dysphoric disorder |
Premenstruell dysfori |
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E.1.1.1 | Medical condition in easily understood language |
Premenstrual dysphoric disorder |
Premenstruell dysfori |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
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 |
The primary objective is to establish if a ulipristal acetate (esmya®) can be used for treatment of PMDD.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include the investigation of neural correlates of symptom relief during SPRM treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
– be essentially healthy – be a woman between 20-45 years of age (i.e. >19 and <46 years) – have a regular menstrual cycle (25-31 days) in the opinion of the investigator – have Caucasian origin and speak Swedish – have PMDD according to DSM-V criteria – willingness to use barrier contraception or cupper intrauterine device, or being sterilized (or partner being sterilized).
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E.4 | Principal exclusion criteria |
– has or has had any steroid hormonal treatment during the previous 3 months – treatment with antidepressive or antipsychotic drugs or other psychopharmaceuticals during the previous 3 months (including over-the-counter or prescription drugs for PMS symptoms) – ongoing psychiatric disease – prior history of severe depression requiring hospitalization – prior history of suicide attempts – Severe medical conditions in the opinion of the investigator that may interfere with compliance to treatment or study procedures – history of drug or alcohol abuse, or use more than 30 g of alcohol per day (corresponds to ~2 glasses of wine/day) – breast-feeding, pregnancy or plans of a pregnancy during the study period – has a clinically relevant finding on the physical examination or blood testing – is working night shifts on a regular basis (rare occasions of night work may be acceptable) – participate concurrently in any other clinical trial – hearing impairments or visual impairment (> 5 degrees myopic/hyperopic or profound astigmatism) – profound fear of confined spaces – Other contraindications for magnetic resonance imaging |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point for measuring the treatment effect will be symptom assessment using a validated daily rating scale, the Daily Record of Severity of Problems (DRSP)
Primary outcome variables
• The primary variable will comprise the change in sum of scores for irritability, depression, tension and lability (DRSP items 1a-4b), i.e. a maximal of 8 x 6 = 48 points possible. • The proportion of women with remission of PMDD will be compared between treatments. Remission is defined as a decrease in severity of symptoms (items 1a-4b) of 75% or more during the late luteal phase days in the treatment cycle compared to the corresponding days during the qualification period.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final 5 days of the luteal phase in treatment cycle 2 and 3. |
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E.5.2 | Secondary end point(s) |
Change in scores for the individual symptoms in the DRSP. Change in total score of all 21 items in the DRSP will be compared between treatments (e.g. Cohen et al 2002; Yonkers et al 2005). Quality of Life, by the EQ-50, will be compared between the two treatments. Brain emotional stimuli processing assessed using functional magnetic resonance imaging (fMRI); Brain resting state activity (rsMRI); Brain morphology measured by MRI. The Montgomery-Asberg Depression Rating Scale (MADRS), the State Anxiety Inventory (STAI), |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The final 7 days of treatment cycle 3. |
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.8.1.6 | Cross over | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |