AVP-825 breath-powered intranasal delivery system in the acute treatment of migraines

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SCIENCE
AVP-825 breath-powered intranasal delivery system in the acute treatment of migraines
Key Take-Away: 

Although oral sumatriptan has been utilized as a common treatment for migraine but  AVP-825 Breath-Powered Intranasal Delivery System have supported the concept of a ‘treat while mild’ paradigm to achieve optimal patient outcomes.

Apart from the fact that migraine is prevalent, yet, studies directly comparing migraine medications have rarely been conducted. Sumatriptan is the most widely prescribed triptan for migraine and is available in different formulations including oral, subcutaneous injection, liquid nasal spray, and suppository.

ABSTRACT: 
Background: 

Apart from the fact that migraine is prevalent, yet, studies directly comparing migraine medications have rarely been conducted. Sumatriptan is the most widely prescribed triptan for migraine and is available in different formulations including oral, subcutaneous injection, liquid nasal spray, and suppository.

It is associated with variable absorption and delayed onset of efficacy, because of slowed gastric emptying during migraine and in migraineurs generally, as well as with triptan-related adverse effects such as tingling, and chest, jaw, or neck tightness. Despite the well established efficacy of triptans many patients remain dissatisfied with existing triptan options due to slow onset of efficacy with oral treatment. A novel intranasal delivery system, AVP-825 delivers sumatriptan more effectively than traditional liquid nasal spray which provides drug distribution across a significantly wider area of absorbent mucosa.

  • Rationale behind research
  1. Previous phases 2 and 3 placebo-controlled AVP-825 trials in acute treatment of migraine showed early onset of efficacy accompanied by sustained headache relief through 48 hours and a low level of triptan-related adverse effects.
  • Objective

To compare the efficacy, tolerability, and safety of AVP-825 an investigational bi-directional breath-powered intranasal delivery system containing low-dose (22 mg) sumatriptan powder, vs. 100 mg oral sumatriptan for acute treatment of migraine.

Methods: 

 

Study outcomes

  • Primary outcome: Headache severity score on a standard ordinal 4 point scale, before the intake of study medication (baseline) and at 30 minutes time points
  • Secondary outcomes: Headache severity score at 10, 15, 30, 45, 60, 90, and 120 minutes post-dose and included pain relief followed by no worsening of pain or second dose of medication.
  • Time-points
    • Efficacy: Baseline, 12 weeks  post intervention
    • Safety: Treatment emergent adverse events, laboratory measures and electrocardiograms was evaluated at 120 minutes post-dose

 

Results: 

 

Baseline: Completion rates for treatment period 1 were 79.7% (AVP-825) and 69.3% (oral sumatriptan) and 85.5% (AVP-825) and 84.2% (oral sumatriptan) for treatment period 2

  • Primary outcomes
  • The primary end-point showed better reduction in migraine pain intensity with AVP-825 vs. oral sumatriptan that was statistically significant over the first 30 minutes post-dose
  • Pain relief and pain freedom at 120 minutes through 24 and 48 hours, were achieved in a similar percentage of attacks for both treatments
  • Fig.1. Percentage of migraine attacks achieving pain relief and sustained pain relief

Fig.2. Pain freedom and sustained pain freedom 

  • Secondary outcomes
  • When pain was mild, moderate and severe, then reduction was greater in AVP-825 vs. sumatriptan at 30 and 45 post-dose
  • For patients treated ≥3 attacks, the efficacy of AVP-825 was greater than 100 mg oral sumatriptan
  • TEAEs were experienced by 53.9% of subjects with AVP-825 and 32% of subjects with oral sumatriptan and most were mild in severity
  • Nasal discomfort and abnormal taste were more common with AVP-825 vs. oral sumatriptan (16% vs. 1% and 26% vs. 4%, respectively), but ∼90% were mild, leading to only one discontinuation
Conclusion: 

This COMPASS study demonstrates that the investigational AVP-825 intranasal delivery system provides an earlier reduction of migraine pain intensity both statistically and clinically significant and higher rates of pain relief and pain freedom within 30 minutes, without loss of sustained efficacy, than the most effective oral sumatriptan (100 mg).

Moreover, AVP-825 showed fewer triptan-related adverse effects than 100 mg oral sumatriptan. The patients were questioned regarding treatment-emergent atypical sensations, and the incidence of these adverse events was significantly lower with AVP-825 than oral sumatriptan, indicating an important clinical difference between the treatments.

Headache 2015; 55:621-635
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