Effect of Ivabradine on Levcromakalim-Induced Symptoms in Individuals With Migraine Without Aura (ILIM)

Inclusion Criteria:

• Be able to give voluntary written informed consent to participate.

• Have a diagnosis of episodic migraine without aura according to The InternationalClassification of Headache Disorders 3rd Edition.

• Be in good general health and without any cardio- or cerebrovascular diseases,psychiatric disorders or other severe comorbidities.

• Be 18-60 years of age.

• Have a weight between 50-100 kg.

• Have a normal standard resting 12-lead ECG at the screening visit with heart rate (HR) ≥ 60 bpm (the inclusion criterium of HR ≥ 60 bpm at screening has previouslybeen used in studies with dosages of ivabradine up to 20 mg as single and multipledoses with no significant adverse events).

• Be without any chronic use of medicine.

• Have a negative urine-human chorionic gonadotropin (hCG) test at the screening visitif they are female of childbearing potential.

Exclusion Criteria:

• Suffer from tension type headache, as defined by the The InternationalClassification of Headache Disorders 3rd Edition, more than five days a month onaverage in the last year.

• Are diagnosed with any primary headache disorder apart from migraine without aura asde-fined in The International Classification of Headache Disorders 3rd Edition (relating to tension type headache, see above).

• Suffer from any headache 48 hours prior to the start of the experiment or anymigraine 72 hours prior to the start of the experiment.

• Are allergic to ivabradine or levcromakalim.

• Are lactose intolerant (due to Ivabradine tablets containing lactose).

• Have a daily intake of any medicine other than oral contraception or use of drugs orother ed-ibles/beverages with potential serious interactions with ivabradine

• Have a history of personal/familial or clinical signs of: cardiovascular andcerebrovascular disease (Long QT Syndrome, Cardiac dysrhythmia, Bradycardia, i.e. aresting heart rate of < 60 bpm at screening, Amnestic information or clinical signsof hyper- or hypotension (Hypertension (systolic blood pressure > 150 mmHg and / ordiastolic blood pressure > 100 mmHg)/Hypotension (systolic blood pressure < 90 mm Hgand / or diastolic blood pressure < 50 mmHg)), Heart failure (NYHA II or higher));Psychiatric conditions; Drug abuse of any kind; Smoking; Other comorbidities orclinical signs of diseases of any kind considered by the investigating physician tomake the participant ineligible because of safety concerns).

• Are pregnant, breastfeeding or not using appropriate contraception.

• Do not want any information on significant pathological findings in the study.