Effect of Riocigaut on Migraine Attack Induction in People With Migraine

Prior treatment

• Any current or previous history of other primary or secondary headache disorder(s) apart from tension type headache ≤ 5 days per month.
• Any daily medication apart from contraceptives.
• Intake of any pro necessitate medication later than 4 times plasma half-life for the specific drug before study start.
• Women of child-bearing potential not currently using safe contraceptives. Women of child-bearing potential does not include hysterectomized women and women who have been in menopause for at least 2 years. Safe contraceptives include either IUD, birth control pills, surgical sterilization of the woman, depositary gestagen, barrier prevention or sexual abstinence.

Other illness

• Use of any antihypertensive, nitrates or nitric oxide donors or phosphodiesterase inhibitors, CYP3A4 and P-glycoprotein inhibitors, HIV-proteaseinhibitors, ciclosporin A or CYP1A1-inhibitors, antacida and acid-neutreulizing agents (such as aluminium-/magnesiumhydroxid), CYP3A4-inductors (such as bosentan, phenytoin, carbamazepin, phenobarbital and herbal remedies with perikon).
• A medical history or clinical signs of
  • Hypertension (systolic blood pressure \>150mmHg and/or diastolic blood pressure \>100mmHg)
  • Hypotension (systolic blood pressure \<100mmHg and/or diastolic blood pressure \<50mmHg)
• A medical history or clinical signs of pulmo-/cardiovascular disease including cerebrovascular disease.
• A family history of severe cardiac disease.
• A medical history or clinical signs of clinically significant psychiatric illness per investigator opinion.
• A medical history or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion.
• Any history of hypersensitivity to riociguat.

Lab values

• Electrocardiogram (ECG) with any clinically significant abnormalities at screening determined by the investigator, including but not limited to, prolonged PQ or QTc interval, signs of arrythmias, ischemia or left/right ventricle dysfunction/hypertrophy.

Other

• Lack of ability to differentiate migraine from other headaches
• Headache within 24 hours before any study related procedures (Provocation Day 1 and Provocation Day 2) - Subjects are however allowed to be re-booked for provocation days according to allowed timelines.
• Pregnant or breastfeeding women
• Positive pregnancy urine screening on screening day or provocation days.
• The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior.
• A medical history or clinical signs of substance or alcohol abuse
• Subjects who do not want information about crucial pathological findings during the study
• Subject likely to not be available to complete all protocol-required study visits or procedures, and/or comply with all required study procedures to the best of the subject and study investigator's knowledge.

• A history of migraine without aura for ≥ 12 months according to the classification criteria of the International Classification of Headache Disorders 3rd Edition (ICHD-3) criteria.
• An estimated average of between 1-5 migraine attacks per month.
• Ability to provide written informed consent and receive participant privacy and rights information prior to initiation of any study-specific activities.
• Male or female participants aged 18-45 years at screening.
• No migraine preventive treatment at screening or during study conduction.
• Non-smokers