Intranasal Delivery of Sumatriptan Powder for Migraine Relief

The novel delivery method may have a more rapid effect on trigeminal nerve pathways, researchers theorize.

LOS ANGELES—Intranasal delivery of sumatriptan powder offers rapid and lasting migraine relief, according to research presented at the 52nd Annual Scientific Meeting of the American Headache Society. The data presented compared sumatriptan delivery via OptiNose, a bi-directional delivery device, with other routes of sumatriptan delivery, including transdermal patch, oral tablets and sprays, nasal sprays, and subcutaneous (SC) injections.

“The OptiNose nasal powder maximizes the clinical effects [of sumatriptan], while minimizing systemic exposure and adverse events,” Per Djupesland, MD, PhD, told Neurology Reviews. “It offers a unique combination of rapid onset of pain relief and long duration of pain freedom, with minimal rate of side effects.”

The OptiNose device (OptiNose AS; Oslo) involves two aspects of nasal anatomy to improve medicine delivery and prevent lung inhalation. To use the device, the patient inserts a disposable unit-dose with a capsule of powdered sumatriptan into the reusable OptiNose body and presses the button, which pierces the capsule. The patient then exhales through the mouth into the device, which releases the particles into one nostril. The positive airway pressure created during exhalation into the device closes off the soft palate, separating the nasal and oral cavities. This allows the use of smaller particles in the nasal passageway, without the risk of lung inhalation. In addition, the closing of the soft palate creates a communication pathway between the two nostrils, allowing air to enter through one nostril and exit through the other after depositing the drug particles.

Rapid and Sustained Relief

A phase II study of OptiNose delivery of sumatriptan published in the August issue of Cephalalgia found that it was “highly effective in treating a single migraine attack.” The randomized, placebo-controlled trial of 117 migraneurs reported that 54% of subjects receiving 10 mg and 57% of subjects receiving 20 mg of intranasal sumatriptan were pain-free at 120 minutes, compared with 25% of the placebo group.

The investigators also noted significant benefits of pain relief, with 84% of the 10-mg group and 80% of the 20-mg group reporting pain relief at 120 minutes compared with 44% of the placebo group, and 73% of the 10-mg group and 74% of the 20-mg group reporting relief at 60 minutes compared with 38% of the placebo group.

The median time to meaningful relief was 54 minutes for the 10-mg group and 50 minutes for the 20-mg group, both of which were significantly faster than the median time of 120 minutes for the placebo group. Sustained pain freedom rates were also high for the sumatriptan groups, with 47% of the 10-mg group and 49% of the 20-mg group reporting freedom from pain at the 48-hour mark.

Intersecting Pain Pathways

The researchers then compared their study results to prior published reports of sumatriptan delivery methods and found that SC injection was the only formulation with similar one-hour pain relief rates.

“Next to SC injection, the OptiNose sumatriptan powder has the most rapid initial rate of absorption,” Dr. Djupesland said. “Delivery of OptiNose sumatriptan powder offers a much broader distribution of the drug to a larger surface of the nasal mucosa (upper posterior segments) than achieved with a spray pump like the one used for the marketed sumatriptan liquid spray.”

Dr. Djupesland noted that sumatriptan absorption in the nasal mucosa was three times greater with OptiNose compared to historical data for the marketed liquid spray. In addition, unlike oral formulations, nasal absorption is not affected by gastric stasis during a migraine. The researchers also noted that although an oral spray has a similar rate of absorption as intranasal delivery, the onset of pain relief is much slower. They speculate that direct actions of nasal sumatriptan on or via branches of the trigeminal nerve may contribute to its rapid efficacy.

“The first branch of the trigeminal nerve (fifth cranial nerve) plays a crucial role as a signaling pathway in migraine,” said Dr. Djupesland. “In the initial phases of migraine, inflammatory mediators in the meningeal nerves cause pain signals to be transported along the first branch of the trigeminal nerve to the brain stem and other more central CNS structures. Following modulation and processing in the CNS, signals are transported in the opposite direction, also through branches of the trigeminal nerve through feedback loops. These cause the typical location of throbbing pain and associated symptoms of migraine typically related to the anatomic locations of trigeminal nerve, and in particular, the first branch.”

 —Rebecca K. Abma

The novel delivery method may have a more rapid effect on trigeminal nerve pathways, researchers theorize.

LOS ANGELES—Intranasal delivery of sumatriptan powder offers rapid and lasting migraine relief, according to research presented at the 52nd Annual Scientific Meeting of the American Headache Society. The data presented compared sumatriptan delivery via OptiNose, a bi-directional delivery device, with other routes of sumatriptan delivery, including transdermal patch, oral tablets and sprays, nasal sprays, and subcutaneous (SC) injections.

“The OptiNose nasal powder maximizes the clinical effects [of sumatriptan], while minimizing systemic exposure and adverse events,” Per Djupesland, MD, PhD, told Neurology Reviews. “It offers a unique combination of rapid onset of pain relief and long duration of pain freedom, with minimal rate of side effects.”

The OptiNose device (OptiNose AS; Oslo) involves two aspects of nasal anatomy to improve medicine delivery and prevent lung inhalation. To use the device, the patient inserts a disposable unit-dose with a capsule of powdered sumatriptan into the reusable OptiNose body and presses the button, which pierces the capsule. The patient then exhales through the mouth into the device, which releases the particles into one nostril. The positive airway pressure created during exhalation into the device closes off the soft palate, separating the nasal and oral cavities. This allows the use of smaller particles in the nasal passageway, without the risk of lung inhalation. In addition, the closing of the soft palate creates a communication pathway between the two nostrils, allowing air to enter through one nostril and exit through the other after depositing the drug particles.

Rapid and Sustained Relief

A phase II study of OptiNose delivery of sumatriptan published in the August issue of Cephalalgia found that it was “highly effective in treating a single migraine attack.” The randomized, placebo-controlled trial of 117 migraneurs reported that 54% of subjects receiving 10 mg and 57% of subjects receiving 20 mg of intranasal sumatriptan were pain-free at 120 minutes, compared with 25% of the placebo group.

The investigators also noted significant benefits of pain relief, with 84% of the 10-mg group and 80% of the 20-mg group reporting pain relief at 120 minutes compared with 44% of the placebo group, and 73% of the 10-mg group and 74% of the 20-mg group reporting relief at 60 minutes compared with 38% of the placebo group.

The median time to meaningful relief was 54 minutes for the 10-mg group and 50 minutes for the 20-mg group, both of which were significantly faster than the median time of 120 minutes for the placebo group. Sustained pain freedom rates were also high for the sumatriptan groups, with 47% of the 10-mg group and 49% of the 20-mg group reporting freedom from pain at the 48-hour mark.

Intersecting Pain Pathways

The researchers then compared their study results to prior published reports of sumatriptan delivery methods and found that SC injection was the only formulation with similar one-hour pain relief rates.

“Next to SC injection, the OptiNose sumatriptan powder has the most rapid initial rate of absorption,” Dr. Djupesland said. “Delivery of OptiNose sumatriptan powder offers a much broader distribution of the drug to a larger surface of the nasal mucosa (upper posterior segments) than achieved with a spray pump like the one used for the marketed sumatriptan liquid spray.”

Dr. Djupesland noted that sumatriptan absorption in the nasal mucosa was three times greater with OptiNose compared to historical data for the marketed liquid spray. In addition, unlike oral formulations, nasal absorption is not affected by gastric stasis during a migraine. The researchers also noted that although an oral spray has a similar rate of absorption as intranasal delivery, the onset of pain relief is much slower. They speculate that direct actions of nasal sumatriptan on or via branches of the trigeminal nerve may contribute to its rapid efficacy.

“The first branch of the trigeminal nerve (fifth cranial nerve) plays a crucial role as a signaling pathway in migraine,” said Dr. Djupesland. “In the initial phases of migraine, inflammatory mediators in the meningeal nerves cause pain signals to be transported along the first branch of the trigeminal nerve to the brain stem and other more central CNS structures. Following modulation and processing in the CNS, signals are transported in the opposite direction, also through branches of the trigeminal nerve through feedback loops. These cause the typical location of throbbing pain and associated symptoms of migraine typically related to the anatomic locations of trigeminal nerve, and in particular, the first branch.”

 —Rebecca K. Abma

The novel delivery method may have a more rapid effect on trigeminal nerve pathways, researchers theorize.

LOS ANGELES—Intranasal delivery of sumatriptan powder offers rapid and lasting migraine relief, according to research presented at the 52nd Annual Scientific Meeting of the American Headache Society. The data presented compared sumatriptan delivery via OptiNose, a bi-directional delivery device, with other routes of sumatriptan delivery, including transdermal patch, oral tablets and sprays, nasal sprays, and subcutaneous (SC) injections.

“The OptiNose nasal powder maximizes the clinical effects [of sumatriptan], while minimizing systemic exposure and adverse events,” Per Djupesland, MD, PhD, told Neurology Reviews. “It offers a unique combination of rapid onset of pain relief and long duration of pain freedom, with minimal rate of side effects.”

The OptiNose device (OptiNose AS; Oslo) involves two aspects of nasal anatomy to improve medicine delivery and prevent lung inhalation. To use the device, the patient inserts a disposable unit-dose with a capsule of powdered sumatriptan into the reusable OptiNose body and presses the button, which pierces the capsule. The patient then exhales through the mouth into the device, which releases the particles into one nostril. The positive airway pressure created during exhalation into the device closes off the soft palate, separating the nasal and oral cavities. This allows the use of smaller particles in the nasal passageway, without the risk of lung inhalation. In addition, the closing of the soft palate creates a communication pathway between the two nostrils, allowing air to enter through one nostril and exit through the other after depositing the drug particles.

Rapid and Sustained Relief

A phase II study of OptiNose delivery of sumatriptan published in the August issue of Cephalalgia found that it was “highly effective in treating a single migraine attack.” The randomized, placebo-controlled trial of 117 migraneurs reported that 54% of subjects receiving 10 mg and 57% of subjects receiving 20 mg of intranasal sumatriptan were pain-free at 120 minutes, compared with 25% of the placebo group.

The investigators also noted significant benefits of pain relief, with 84% of the 10-mg group and 80% of the 20-mg group reporting pain relief at 120 minutes compared with 44% of the placebo group, and 73% of the 10-mg group and 74% of the 20-mg group reporting relief at 60 minutes compared with 38% of the placebo group.

The median time to meaningful relief was 54 minutes for the 10-mg group and 50 minutes for the 20-mg group, both of which were significantly faster than the median time of 120 minutes for the placebo group. Sustained pain freedom rates were also high for the sumatriptan groups, with 47% of the 10-mg group and 49% of the 20-mg group reporting freedom from pain at the 48-hour mark.

Intersecting Pain Pathways

The researchers then compared their study results to prior published reports of sumatriptan delivery methods and found that SC injection was the only formulation with similar one-hour pain relief rates.

“Next to SC injection, the OptiNose sumatriptan powder has the most rapid initial rate of absorption,” Dr. Djupesland said. “Delivery of OptiNose sumatriptan powder offers a much broader distribution of the drug to a larger surface of the nasal mucosa (upper posterior segments) than achieved with a spray pump like the one used for the marketed sumatriptan liquid spray.”

Dr. Djupesland noted that sumatriptan absorption in the nasal mucosa was three times greater with OptiNose compared to historical data for the marketed liquid spray. In addition, unlike oral formulations, nasal absorption is not affected by gastric stasis during a migraine. The researchers also noted that although an oral spray has a similar rate of absorption as intranasal delivery, the onset of pain relief is much slower. They speculate that direct actions of nasal sumatriptan on or via branches of the trigeminal nerve may contribute to its rapid efficacy.

“The first branch of the trigeminal nerve (fifth cranial nerve) plays a crucial role as a signaling pathway in migraine,” said Dr. Djupesland. “In the initial phases of migraine, inflammatory mediators in the meningeal nerves cause pain signals to be transported along the first branch of the trigeminal nerve to the brain stem and other more central CNS structures. Following modulation and processing in the CNS, signals are transported in the opposite direction, also through branches of the trigeminal nerve through feedback loops. These cause the typical location of throbbing pain and associated symptoms of migraine typically related to the anatomic locations of trigeminal nerve, and in particular, the first branch.”

 —Rebecca K. Abma