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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065540 |
E.1.2 | Term | Menstrual migraine |
E.1.2 | System Organ Class | 100000004852 |
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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 evaluate the effect of two different doses (10 mg and 16 mg) of sepranolone on number of menstrual migraine days compared with placebo in patients with menstrual migraine. |
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E.2.2 | Secondary objectives of the trial |
To investigate the treatment efficacy of Sepranolone as assessed by amount of symptomatic treatment needed
To evaluate the effect of two different doses (10 mg and 16 mg) of sepranolone on number of menstrual migraine days in patients with menstrual migraine.
To investigate the responder rate of Sepranolone on menstrual migraine
To investigate the effect of Sepranolone on auxiliary migraine symptoms
To evaluate the effect of Sepranolone on menstrual migraine related physical and functional impairment in women with menstrual migraine
To evaluate the effect of Sepranolone on the impact of menstrual migraine on everyday activities in patients with menstrual migraine
To evaluate the effect of Sepranolone on the impact of menstrual migraine on overall daily activities in women with menstrual migraine
To measure Sepranolone exposure
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main Inclusion Criteria
The woman must:
1. provide her informed consent prior to any study related procedures
2. be aged ≥18 and ≤45 years.
3. have a regular menstrual cycle of 24-35 days
4. use sufficient barrier contraception, non-hormonal IUD, be truly abstinent or the woman or her male sexual partner has been surgically sterilized (further described in Section 4.3.1).
5. have a history of migraine according to the IHS classification ICHD-3 with a history of at least 12 months with migraine in conjunction with menstruation and in at least 2 out of 3 ovulatory menstrual cycles.
6. for randomisation, have documented menstrual migraine attacks during at least two menstrual cycles out of the three-cycle screening and baseline period. A menstrual migraine attack is defined as starting at a time between Day -2 and Day +3 of full menstrual flow (limits inclusionary)
Further, the woman may
7. have a total of maximum ten (10) migraine or other headache days per month.
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E.4 | Principal exclusion criteria |
Main Exclusion Criteria
The woman must not have:
1. participated in a clinical study and received active drug in such a study within 30 days or 5 study drug half-lives, whichever the longest, prior to the first study visit.
2. in the investigator's opinion, evidence and/or history of any clinically significant neurological disease, other intracranial or systemic diseases or conditions potentially interfering with study assessments
3. a BMI >35 kg/m2.
4. or has had a malignant disease within the previous 5 years (except non-melanoma skin cancer, cervical or breast ductal carcinoma in situ)
5. HIV or ongoing hepatitis by history
6. have allergies to ingoing study drug components or a history of anaphylactic reactions.
7. have a less than 80% compliance with eDiary reporting during Days -7 until + 7 in each of the three-cycle baseline periods.
The woman must not be:
8. suffering any other medically significant and unstable disease potentially interfering with or being negatively affected by participation in the study, as judged by the investigator.
9. pregnant or breast-feeding, or planning pregnancy during the study period
10. taking any systemic steroid hormonal treatment (including hormonal IUD) during 3 months before the study visit. Topical corticosteroids and stable doses of inhalational treatment for asthma or seasonal allergy may be allowed. For injectable hormonal contraceptives, a 6-month washout is required.
11. previously been diagnosed with a major psychiatric disorder according to DSM 5® criteria, including drug abuse or dependency
12. taking disallowed medications or allowed with restrictions with respect to their use prior to or during the study (this list is not comprehensive). Disallowed medications include: corticosteroids, OCTs, over-the-counter or prescription drugs for PMS symptoms, including but not limited to, bioidentical hormones, St John’s wort, Evening primrose oil, Agnus castor.
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction in the menstrual cycle mean number of menstrual migraine Days.
The menstrual cycles need to be ovulatory as demonstrated by mid-luteal phase elevated progesterone levels.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During Day -2 to Day +5 of three menstrual cycles, compared to baseline. |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in the menstrual cycle number of doses of rescue symptomatic medication taken.
2. Change from baseline of the menstrual cycle mean number of migraine Days.
3. Change from baseline of the menstrual cycle mean number of days with moderate or severe migraine.
4. Change from baseline of number of days with moderate or severe migraine.
5. Proportion of women having 30%-50%-75%-100% or more reduction in number of migraine Days.
6. Change from baseline in the menstrual cycle auxiliary migraine symptoms in patients’ reporting of associated symptoms (nausea, vomiting, photophobia, phonophobia)
7. Change from baseline in the menstrual cycle on the Migraine Physical Function Impact Diary score during Day –2 – Day +5.
8. Change from baseline in the menstrual cycle on the composite functional endpoint/ MM scale Change from baseline in Migraine Physical Function Impact Diary score.
9. Change from baseline in the menstrual cycle on the global impact on daily activities endpoint/ MM scale Change from baseline in Migraine Physical Function Impact Diary score.
10. Plasma levels of isoallopregnanolone. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 and 9 During Day -2 to Day +5 during three consecutive menstrual cycles.
2. Between Day -2 to Day +5 during the last two out of three consecutive menstrual cycles.
3. Between Day -2 to Day +5 during three consecutive menstrual cycles.
4. Between Day -2 to Day +5 during the last two out of three consecutive menstrual cycles.
5. During Days -2 to Day +5 vs. baseline.
8. 6, 7 and 9 During three consecutive menstrual cycles
6, 7 and 9 During the last two out of three consecutive menstrual cycles.
8. During Day –2 – Day +5 during the last two out of three consecutive menstrual cycles.
10. Blood sampling done on Day -7 ±2 during screening and 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 | 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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |