STOP 301: A Phase 3, open-label study of safety, tolerability, and exploratory efficacy of INP104, Precision Olfactory Delivery (POD® ) of dihydroergotamine mesylate, over 24/52 weeks in acute treatment of migraine attacks in adult patients

Abstract

Objective: To report the safety, tolerability, exploratory efficacy, and patient acceptability of INP104 for the acute treatment of migraine from the Phase 3 STOP 301 trial.

Background: Dihydroergotamine (DHE) has long been used to treat migraine, but intravenous administration is invasive, frequently associated with adverse events (AEs), and not suitable for at-home administration. INP104 is an investigational drug device that delivers DHE mesylate to the upper nasal space using a Precision Olfactory Delivery technology and was developed to overcome the shortcomings of available DHE products.

Methods: STOP 301 was an open-label, 24-week safety study, with a 28-week extension period. After a 28-day screening period where patients used their "best usual care" to treat migraine attacks, patients were given INP104 (1.45 mg) to self-administer nasally with self-recognized attacks. The primary objective of this study was to assess safety and tolerability, with a specific focus on nasal mucosa and olfactory function. Exploratory objectives included efficacy assessments of migraine measures and a patient acceptability questionnaire.

Results: A total of 360 patients entered the 24-week treatment period, with 354 patients dosing at least once. INP104-related treatment-emergent AEs were reported by 36.7% (130/354) of patients, and 6.8% (24/354) discontinued treatment due to AEs over 24 weeks. No new safety signals were observed following delivery to the upper nasal space. Pain freedom, the most bothersome symptom freedom, and pain relief at 2 h post-INP104 were self-reported by 38.0% (126/332), 52.1% (173/332), and 66.3% (167/252) of patients, respectively. A low recurrence rate at 24 and 48 h was observed (7.1% [9/126] and 14.3% [18/126], respectively). Most patients found INP104 easy to use and preferred it over their current therapy.

Conclusions: INP104 has the potential to deliver rapid symptom relief, without injection, that is well tolerated and suitable for outpatient use. Results suggest INP104 may be a promising treatment for patients with migraine.

Keywords: Precision Olfactory Delivery; dihydroergotamine; efficacy; migraine; safety/tolerability; upper nasal space.

FIGURE 1

Study design. HIT‐6, Headache Impact Test‐6; MIDAS, Migraine Disability Assessment; UPSIT, University of Pennsylvania Smell Identification Test; wk, week

FIGURE 2

Patient disposition. ^aA patient is counted multiple times if multiple inclusion/exclusion criteria failed. ^bIncluded all patients who signed the ICF and were provided INP104. ^cIncluded all patients who were enrolled and received at least one dose of INP104. ^dIncluded all patients who signed the extension ICF at the Week 24 visit to continue into the extension and were provided with INP104. ^eIncluded all patients who were enrolled, received at least one dose of INP104 in the additional 28‐week treatment period, and signed the extension ICF. ^fIncluded patients who continued INP104 treatment throughout the study period. ICF, informed consent form

FIGURE 3

Two‐hour pain and most bothersome symptom (MBS) freedom from the first migraine attack treated with INP104 and the last migraine attack treated with best usual care at baseline (full safety set). ^aTwenty‐one patients did not provide data and were excluded from the analysis. ^bFifteen patients did not provide data and were excluded from the analysis

FIGURE 4

Pain and most bothersome symptom (MBS) freedom by INP104 treatment time for the first INP104‐treated migraine attack (full safety set). Although 354 patients treated at least one migraine with INP104, only 332 patients treated their first migraine with INP104, of whom 244 treated within 2 h and are therefore not represented in this figure

FIGURE 5

Pain relief for the first INP104‐treated migraine attack (full safety set). Only patients with Time 0 pain assessments and pain assessments at the posttreatment time points are included in the analysis

FIGURE 6

Recurrence rates for the first INP104‐treated migraine attack (full safety set). The eDiary did not capture 24‐ and 48‐h pain measurements if a patient was pain free at 2 h. Hence, a migraine is considered as having recurred if it was pain free at 2 h after INP104 administration and there was onset of a new headache prior to 24 or 48 h after INP104 administration