MTR-106 - Migraine

Migraine Headaches

Migraine headaches are one of the most common problems seen in emergency departments and doctors' offices. The condition is believed to be caused by changes in the brain and the surrounding blood vessels.

Some Migraine Facts and Figures

· Migraine is the most common neurological condition in the developed world, more prevalent than diabetes, epilepsy and asthma combined.

· About 15% of the world's population (including more than 37 million Americans) suffer from migraine symptoms such as headache pain, photophobia, phonophobia and nausea. It is the 3rd most prevalent illness in the world.

· Healthcare and lost productivity costs associated with migraine are estimated to be as high as $36 billion annually in the U.S. alone.

· Living with migraine is a challenge to both the patient's health and his or her social well-being. TrioxBio's Ravimig is expected to reduce this widespread health problem by becoming a global leading therapy for migraine.

Migraine headaches typically last from 4-72 hours and vary in frequency from daily to less than one per year. According to the National Headache Foundation, over 37 million Americans suffer from migraines, and it affects three times as many women as men. About 70-80% of migraine sufferers (called migraineurs) share the condition with other family members.

There are different types of migraines:

· Common migraines, accounting for 80% of all occurrences. There is no "aura" before a common migraine.

· Classic migraines, where the patient experiences an "aura" before the headache. Most often, an aura is a visual disturbance, such as outlines of lights or jagged light images. Classic migraines are usually much more severe than common migraines.

· Status migrainosus is a migraine attack that lasts more than 72 hours.

The exact causes of migraine headaches are not clearly understood, although experts believe they are due to a combination of the expansion of blood vessels and the release of certain chemicals which cause inflammation and pain.

Perivascular nerve activity results in the release of substances such as substance P, neurokinin A, calcitonin gene-related peptide, and nitric oxide, which interact with the blood vessel wall to produce dilation protein extravasation and sterile inflammation. This stimulates the trigeminocervical complex, as shown by the induction of c-fos antigen via a PET scan. Information is then relayed to the thalamus and cortex for registering the pain. Involvement of other centers may explain the associated autonomic systems and affective aspects of this pain.

Induction of migraine attacks by NO-donors isosorbide mononitrate (ISMN), and glyceryl trinitrate (GTN), a pro-drug for NO:

 

2001-2002:Exploratory study on the safety ofMTR-106 for the treatment of acute migraine attacks, Moldova (Eastern Europe), (GMP)

·       68% of the patients treated with MTR-106 (77%) if excluding the lowest dose of 10 mg.) versus 50% of the patients treated with Sumatriptan responded within 2 hours. (Response was measured as moving from severe or moderate headache pain to mild or no pain.)

·       No dose-response relationship could be established. MTR-106 was efficacious at all dosage amounts from 20-100 mg.

·  No dangerous side effects were observed. A mild increase in blood pressure and a mild decrease in heart rate were noted, but were not accompanied by clinical symptoms.

 

2006-2007:Phase II study, (GCP-like, GMP, GLP) A Phase II randomized, double-blind, placebo-controlled, dose-escalating study to assess the pharmacokinetics and pharmacodynamics of MTR-106 tablets for the treatment of Acute Migraine Attack (AMA) without aura in females.

• Safety – No serious adverse events were reported during the study.

• Efficacy – Primary endpoint of pain relief * within 2 hours was achieved and a clear signal of efficacy was obtained.

·       Patients treated with 25 mg. of Ravimig®showed significantly more pain relief than those treated with a placebo (87.5% and 25.0%, respectively; p=0.041)

·       Patients treated with 25 mg. of Ravimig® also showed more sustained pain relief after 24 hours than those treated with a placebo (62.5% and 37.5%, respectively)

• Efficacy – Conclusion Ravimig® was safe, well-tolerated and efficacious in the treatment of acute migraine headaches, attained efficacy rates more elevated than currently used migraine medication (Triptans), and displayed its improved safety profile.

*Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001;358(9294):1668-75

**Tfelt-Hansen PC and Jes Olesen J. The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials.  J Headache Pain. 2012 Jun; 13(4): 271–275.

2007-2008:Post-marketing study