Intervention: Timolol
Trial phase: Phase 2
ATC code: C07AA06 | C07BA06 | C07DA06 | S01ED01 | S01ED51
SMILES: [H][C@](O)(CNC(C)(C)C)COc1nsnc1N1CCOCC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 19
Group description: Participants will be given 0.5% timolol ophthalmic solution to use after migraine onset. Participants will put 2 drops of solution in each eye after migraine and then again 2 hours later if needed or headache persists.

Timolol: Timolol is a clear solution supplied in a plastic ophthalmic dispenser.
Eligibility criteria:
Inclusion Criteria:

Diagnosis of migraine, with or without aura, according to ICHD-2 criteria (Appendix A) for at least 1 year prior to screening; experience an average of 1 to 8 migraines per month.
Females must be practicing an effective method of birth control before entry and throughout the study, or be surgically sterile, or be postmenopausal
Females of child-bearing potential must have a negative urine pregnancy test
Subjects should be able to demonstrate the ability to properly administer study medication
Subjects should be able and willing to read and comprehend written instructions and complete the diary information required by the protocol
Subjects must be capable, in the opinion of the Investigator, of providing informed consent or assent to participate in the study
Subjects (and their legally acceptable representatives, if applicable) must provide an informed consent indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

Inability to distinguish other headaches from migraine
Experiences headache of any kind at a frequency greater than or equal to 15 days per month
Current use of medication for migraine prophylaxis that has not been stable (no dose adjustment) for 30 days prior to screening
Chronic opioid therapy for headaches (> 3 consecutive days in the 30 days prior to screening)
Hemiplegic migraine
History, symptoms or signs of ischemic cardiac, cerebrovascular or peripheral vascular syndromes
History of glaucoma and/or current treatment with prescription eye drops
History of naso-lacrimal duct ("tear duct problem" to patients) obstruction or surgery for such
Active treatment by ophthalmologist or optometrist for any severe ophthalmic disease or problem
Any physical problems or co-ordination difficulty or eye avoidance sensitivity ("squeezer") that would preclude proper installation of eye drops in either or both eyes
History of uncontrolled asthma, COPD, or reversible airway disease which in the opinion of the investigator would be worsened by the use of beta blockers
History of clinically symptomatic bradycardia, congestive heart failure, or hypotension
Uncontrolled Diabetes Mellitus
Uncontrolled Hyperthyroidism
History (within 2 years) of drug or alcohol abuse
Systemic disease, which in the opinion of the Investigator, would contraindicate participation
History of a neurological or psychiatric condition, which in the opinion of the Investigator would contraindicate participation
History of hypersensitivity or intolerance to beta-blockers eye drops
Pregnant or lactating women
Have taken any investigational medication within 12 weeks before randomization, or are scheduled to receive an investigational drug
Subjects, who in opinion of the Investigator, should not be enrolled in the study because of the precautions, warnings or contra-indications sections of the timolol Package Insert