ZOMIG(R) Nasal Spray Provides Total Relief From All Migraine Symptoms, Study Shows

Main Category: Headache / Migraine
Article Date: 14 Jan 2005 - 0:00 PDT

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Results of the first study ever to assess efficacy across all symptoms commonly experienced during a migraine attack found that treatment with ZOMIG(R) (zolmitriptan) Nasal Spray produced a significantly higher rate of total symptom relief, defined as freedom from pain, nausea, and sensitivity to light and sound, at one hour after the first dose compared to placebo.(1) The study, published this month in the American Headache Society's peer-reviewed journal Headache, examined patients in a setting closely resembling normal clinical practice where patients were free to treat an attack of any baseline intensity and at any time after onset.

"This is the first migraine study ever to look at total symptom relief at one hour compared to placebo," said Marek Gawel, MB BCh, FRCPC, consulting neurologist, Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada and lead investigator of the REALIZE (Real Life Intranasal Zolmitriptan Exposure) study. "Historically, migraine studies have looked only at reducing headache pain and not the range of equally debilitating symptoms that can disrupt daily life activities."

The total symptom relief rate one hour postdose was significantly higher in patients using ZOMIG Nasal Spray than those using placebo (14.5% vs 5.1%; P<0.0001). Within 30 minutes postdose, nearly three times as many treated patients experienced total symptom relief (6.1% vs 2.1% for placebo; P<0.01), and about one-third of the patients using ZOMIG Nasal Spray experienced total symptom relief by two hours after treatment (32.6% vs 8.5% for placebo; P<0.0001).

Almost half of patients treated with ZOMIG Nasal Spray reported the impact of migraine on normal activities was significantly reduced at two hours post-treatment (46.7% vs 18.7% for placebo; P<0.0001) and this result was consistent among subgroups of patients with mild (67.9% vs 21.2%), moderate (44.4% vs 18.5%) and severe (46.7% vs 18.4%; P<0.0001) baseline pain intensity. Most notably, one-third of ZOMIG Nasal Spray patients with headache of severe baseline intensity were able to perform normal activities 30 minutes postdose (32.5% vs 17.0% for placebo; P=0.0118).

STUDY RESULTS SUMMARY

Total Symptom Relief

Overall, the two-hour total symptom relief rates were higher in the ZOMIG Nasal Spray patients versus the placebo group among patients with a baseline headache intensity of mild (61.3% vs 15.8%), moderate (33.2% vs 9.0%) or severe (23.9% vs 4.8%).

Headache Response

In patients with moderate or severe baseline headache intensity, headache response, defined as a reduction in pain from moderate or severe intensity to mild or none, was assessed. ZOMIG Nasal Spray produced a significantly higher headache response rate than placebo from 10 minutes (15.1% vs 9.1%; P=0.0079).

The headache response rate with ZOMIG Nasal Spray reached a value of 64.8% by two hours postdose vs 23.9% for placebo (P<0.0001). High two-hour headache response rates were seen with ZOMIG Nasal Spray treatment among both patients with moderate (67.1% vs 28.0% for placebo) and severe (59.0% vs 12.4% for placebo) baseline headache intensity.

Pain-Free Status

At all timepoints, the proportion of patients who were pain-free was higher in the ZOMIG Nasal Spray group than in the placebo group. The difference between the ZOMIG Nasal Spray and placebo groups was significant from 30 minutes (7.7% vs 3.2%; P=0.0039). At two-hours postdose, over one-third of patients in the ZOMIG Nasal Spray group were pain-free (35.7%), compared with only 9% of patients in the placebo group (P<0.0001). Two-hour pain-free rates with ZOMIG Nasal Spray compared with placebo split by baseline headache intensity were 64.5% vs 15.8% for mild, 36.3% vs 9.3% for moderate and 27.4% vs 5.7% for severe. The corresponding rates at one hour were 43.8% vs 8.3%, 15.5% vs 5.6% and 14.5% vs 5.6%, respectively, and at 30 minutes were 25.8% vs 2.6%, 6.1% vs 3.4% and 6.9% vs 2.9%, respectively.

Sustained Pain-Free Status

Sustained pain-free status was defined as being pain-free at two hours postdose, with no worsening between 2 and 24 hours and no use of a second dose of study medication or escape medication within 24 hours. Sustained pain-free status at 24 hours was achieved in 23.9% of ZOMIG Nasal Spray recipients, compared with 7.4% of placebo recipients (P<0.0001). This substantial difference versus placebo was maintained for attacks with a baseline pain intensity of mild (32.3% vs 10.8% for placebo), moderate (24.9% vs 7.4% for placebo) or severe (19.3% vs 6.1% for placebo; P=0.0069).

Safety and Tolerability

ZOMIG Nasal Spray was generally well tolerated in study patients, and adverse events were transient and mostly mild or moderate in intensity. The most common adverse event reported was unusual taste (dysgeusia) by 15.9% of patients, which led to premature withdrawal from the study in only one patient. Other common adverse events reported included nasal passage irritation (6.3%), dizziness (6.0%), throat irritation (5.4%) and fatigue (5.2%).

About the REALIZE Study

The REALIZE study is an international, multicenter, two-phase study of ZOMIG 5 mg Nasal Spray in the acute treatment of migraine. Phase 1 of the study was a randomized, double-blind comparison of ZOMIG Nasal Spray versus placebo in the treatment of a single migraine attack, and enrolled 1,044 patients. The intent-to-treat population comprised 461 ZOMIG Nasal Spray patients and 451 placebo recipients.

The primary efficacy endpoint was total symptom relief (freedom from pain, nausea, photophobia and phonophobia) one hour after the first dose, irrespective of baseline pain intensity. Secondary efficacy endpoints included total symptom relief at other timepoints, as well as headache response (in patients with moderate or severe baseline intensity), pain-free status and sustained pain-free status, reduction in impact on normal activities and ability to perform normal activities.

Patients were permitted to treat a single attack with any baseline intensity, at any time after onset, but could only treat an attack with the study drug if at least 24 hours had passed since the previous attack, regardless of whether medication had been taken for the previous attack.

Patients were permitted to use a second dose of study medication or an agreed escape medication if adequate pain relief had not been obtained two hours after the initial dose. Diary cards were used to record efficacy data relating to the attack treated with the study medication and were reviewed with the investigator within seven days of treating a migraine attack.

This study was supported by a grant from AstraZeneca.

About ZOMIG(R) (zolmitriptan)

ZOMIG (zolmitriptan) Nasal Spray was approved by the U.S. Food and Drug Administration in September 2003. ZOMIG Nasal Spray is an effective and fast-acting noninjectable triptan therapy. Pharmacokinetic studies show that ZOMIG is detectable in the plasma 5 minutes postdose and in the brain in 5 minutes.(2) This nonoral route of administration and direct absorption from within the nasal cavity are potential benefits for patients requiring rapid relief and for those with nausea, vomiting, or who prefer not to administer an injection. In addition, ZOMIG Nasal Spray is well tolerated(3) and is supplied in an easy-to-use, convenient device.

Zolmitriptan belongs to the class of medications known as triptans, which are selective serotonin receptor agonists. ZOMIG is also available in two other formulations: ZOMIG(R) (zolmitriptan) Tablets and ZOMIG-ZMT(R) (zolmitriptan) Orally Disintegrating Tablets. ZOMIG is available in more than 80 countries and is the most prescribed triptan in the top five European markets (France, Germany, Italy, Spain and the UK).(4)

ZOMIG(R) Tablets, ZOMIG-ZMT(R) Orally Disintegrating Tablets, and ZOMIG(R) Nasal Spray are indicated for the acute treatment of migraine with or without aura in adults. ZOMIG is not intended to prevent migraine attacks but to relieve pain regardless of when the migraine attack occurs.

ZOMIG is contraindicated for patients with uncontrolled hypertension, ischemic heart disease, or other significant underlying heart disease. In addition, ZOMIG should not be administered to patients who are hypersensitive to zolmitriptan or any of the inactive ingredients of ZOMIG. ZOMIG is not intended for the prophylactic therapy of migraine or for the management of hemiplegic or basilar migraine.

ZOMIG should not be taken by patients who have certain types of heart disease or uncontrolled high blood pressure. Very rarely, some people without recognized heart disease may have serious heart-related problems. Patients who think they may have risk factors for heart disease such as smoking, high blood pressure, high cholesterol, or a family history of heart disease, or if they are pregnant, nursing, or taking medications should talk to their healthcare provider. Phenylketonuric patients should be informed that ZOMIG-ZMT contains phenylalanine, a component of aspartame.

The most common side effects associated with taking oral ZOMIG include dizziness; tightness, pressure or pain in the neck, throat, or jaw; fatigue; tingling sensations; drowsiness; and nausea. The most common side effects of ZOMIG Nasal Spray are unusual taste, dry mouth, tingling sensation, skin sensitivity, especially around the nose, pain, pressure, and tightness sensations (e.g., in the nose, throat, or chest), drowsiness, weakness, dizziness and nausea.

For full prescribing information, please visit http://www.zomig.com.

About MedPointe Pharmaceuticals

MedPointe Pharmaceuticals is a privately held specialty pharmaceutical company located at 265 Davidson Avenue, Suite 300, Somerset, New Jersey, 08873-4120; 732-564-2200. MedPointe specializes in respiratory, allergy, central nervous system, cough-cold, and pediatric products. The company maintains a manufacturing facility in Decatur, Illinois. For more information on MedPointe, visit www.medpointepharma.com.

ZOMIG(R) and ZOMIG-ZMT(R) are registered trademarks of the AstraZeneca group of companies. MedPointe markets and sells ZOMIG in the U.S. in accordance with a marketing distributorship with AstraZeneca Pharmaceuticals.

Contact Information: MCS Public Relations

800-477-9626
Carol Cartwright: carolc@mcspr.com
Noelle Piscitelli: noellep@mcspr.com,

(1) Gawel M, Aschoff J, May A, Charlesworth B. Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute treatment of migraine: results from phase 1 of the REALIZE study. Headache. 2005;45:7-16.

(2) Wall A, Kagedal M, Nilsson D., Yates R, Langstrom B, Bergstrom M. An open-label positron emission tomography study to investigate the distribution of intranasally administered 11-C zolmitriptan into the CNS. European Journal of Neurology. 2003;10(Suppl 1):S36. (Abstract).

(3) Dowson AJ, Charlesworth BR, Purdy A, Becker WJ, Boes-Hansen S, Farkkila M. Tolerability and consistency of effect of zolmitriptan nasal spray in a long-term migraine treatment trial. CNS Drugs. 2003;17(11);839-851.

(4) IMS Health MIDAS data, 2004.

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