PK&tolerability of IV&inhaled Dihydroergotamine in smokers&non-smokers

• Research type

  Research Study

• Full title

  An Open-Label, 2-Period, Crossover Phase 2 Study Comparing the Pharmacokinetics and Tolerability of Dihydroergotamine Mesylate (DHE) Delivered Intravenously (DHE 45) and by Oral Inhalation (MAP0004) in Smoking and Non-Smoking Adult Volunteers

• IRAS ID

  36755

• Contact name

  Salvatore Febbraro

• Sponsor organisation

  MAP Pharmaceuticals, Inc.

• Eudract number

  2009-016732-12

• ISRCTN Number

  1

• Research summary

  According to International Headache Society (IHS) diagnostic criteria, the prevalence of migraine has been reported to be 17.6% of females and 5.7% of males within the adult population. An estimated 28 million Americans have acute migraine attacks. Less than half receive optimal medical care. There is still an important unmet need in treating migraine despite the availability in the last 15 years of numerous triptans that bind selectively to the 5 HT1B and 5 HT1D receptors. Triptans offer good efficacy and tolerability and, with several alternative formulations (intranasal and subcutaneous injection), they can overcome the gastric stasis, nausea, and vomiting that commonly accompany migraine. However, triptans have several short-comings including lack of universal efficacy (approximately 70%), inconsistency of response, slow onset of action when administered orally, high recurrence rate and potential for Medication Overuse Headache. Thus, despite the substantial market triptans command, alternative effective classes of anti migraine drugs remain necessary. DHE has been used for the treatment of migraine for over 60 years since it was first introduced in 1946. DHE binds with high affinity to 5 HT1B and 5 HT1D receptors as well as to serotonin 5 HT1A, 5 HT2A and 5 HT2C receptors, norepinephrine a2A, a2B and a1 receptors, and dopamine D2 and D3 receptors. The therapeutic activity of DHE in migraine is generally attributed to the agonist effect at 5 HT1B and 5 HT1D receptors on the intracranial blood vessels causing vasoconstriction of dural arterio venous anastomoses, on trigeminal system nerve endings, inhibiting release of pro inflammatory neuropeptide, and on trigeminal nucleus caudalis inhibiting pain transmission. MAP Pharmaceuticals, Inc., (hereafter, MAP) has developed MAP0004, an orally, inhaled formulation of dihydroergotamine mesylate (DHE) in hydfluroalkane [HFA] propellants, to be used with the proprietary, breath actuated Tempo?½ inhaler. The Tempo inhaler is expected to deliver most of the drug consistently to the deep lung while minimizing oropharyngeal deposition. MAP anticipates that the intrapulmonary DHE dosage form will allow consistent dosing with a limited number of actuations, fast onset of pain relief, and a sustained 24 hour migraine free period following administration. The ease of use and portability of the Tempo inhaler is expected to allow timely self administration of the MAP0004, with or without healthcare professional intervention.

• REC name

  Wales REC 2

• REC reference

  09/WSE02/55

• Date of REC Opinion

  13 Nov 2009

• REC opinion

  Favourable Opinion