There was a numerically superior benefit for subjects in group B vs group A at 2 hours and a statistically significant benefit in favor of naproxen sodium at 8 hours vs SumaRT/Nap during the first month of the study when subjects were taking their study medication daily as a preventative. Subjects who withdrew prematurely from the study did not experience significant

relief of headache until 8 hours post-dose, and at 8 hours their level of relief was inferior to those subjects completing the study per protocol. During months 2 and 3, SumaRT/Nap was statistically superior to naproxen sodium (Fig. 4 —). At baseline, all doses of acute medication used during the 1-month run-in period were recorded and compared to study medications used in CB-839 chemical structure months 1 see more through 3. During baseline, subjects used their usual preferred medications, and nearly all subjects used more than one acute medication during the baseline period. The most common medications used were triptans and NSAIDs. Of the subjects randomized into the study, 12/20

(60%) subjects were using a triptan greater than 10 days and 2/20 (10%) were using an NSAID greater than 15 days during the baseline period. These subjects were technically in MO, but not experiencing a worsening of migraine and thus not considered to be in MOH. One subject was using an opioid for 8 days during that month. During month 1, subjects were required to take study medication daily as a preventative, which increased the number of doses of medication used compared to baseline. Per protocol, subjects were permitted to take a second dose of study medication as needed for acute treatment. Subjects in group A took

a second dose of medication more often than those in group B. During months 2 and 3, there was a reduction in doses of acute medication for both groups compared to baseline and month 1. The reduction in acute medication for group B was superior to group A for months 2 and 3 for subjects completing the study per protocol (Fig. 5 —). The percentage of subjects who fell under the definition MCE of MO at the end of 3 months was 14/15 (93%) in group A (using a triptan 10 or more days per month) and 1/5 (20%) in group B (using a naproxen greater than 15 days per month). Of the 26 subjects in the baseline population that were randomized, 3 had an increase in headache days in month 1 over baseline; 2 of these subjects decreased in headache days in months 2 and 3; the third persisted with daily headaches through baseline and all 3 months of active study and used study drug twice daily from randomization through month 3. The subject reported via diary that she was doing better and finding the medication helpful with her daily migraine. Post hoc review of this specific subject revealed use of any acute medication on only 4 days during baseline to treat daily CM. However, during the 3-month active phase of the study, this subject used SumaRT/Nap twice daily.