Abstract
Objective: To better understand the utility of using pain freedom and most bothersome headache-associated symptom (MBS) freedom as co-primary endpoints in clinical trials of acute migraine interventions. Background: Adhesive dermally applied microarray (ADAM) is an investigational system for intracutaneous drug administration. The recently completed pivotal Phase 2b/3 study (ZOTRIP), evaluating ADAM zolmitriptan for the treatment of acute moderate to severe migraine, was one of the first large studies to incorporate MBS freedom and pain freedom as co-primary endpoints per recently issued guidance by the US Food and Drug Administration. In this trial, the proportion of patients treated with ADAM zolmitriptan 3.8 mg, who were pain-free and MBS-free at 2 hours post-dose, was significantly higher than for placebo. Methods: We undertook a post-hoc analysis of data from the ZOTRIP trial to examine how the outcomes from this trial compare to what might have been achieved using the conventional co-primary endpoints of pain relief, nausea, photophobia, and phonophobia. Results: Of the 159 patients treated with ADAM zolmitriptan 3.8 mg or placebo, prospectively designated MBS were photophobia (n=79), phonophobia (n=43), and nausea (n=37). Two-hour pain free rates in those with photophobia as the MBS were 36% for ADAM zolmitriptan 3.8 mg and 14% for placebo (P=.02). Corresponding rates for those with phonophobia as the MBS were 14% and 41% (P=.05). For those whose MBS was nausea, corresponding values were 56% and 16%, respectively (P=.01). Two-hour freedom from the MBS for active drug vs placebo were 67% vs 35% (P<.01) for photophobia, 55% vs 43% (P=.45) for phonophobia, and 89% vs 58% for nausea (P=.04). MBS freedom but not pain freedom was achieved in 28%. Only 1 patient (1%) achieved pain freedom, but not MBS freedom. The proportion with both pain and MBS freedom was highest (56%) among those whose MBS was nausea. Conclusion: In this study, the use of MBS was feasible and seemed to compare favorably to the previously required 4 co-primary endpoints.
| Original language | English (US) |
|---|---|
| Journal | Headache |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- Adhesive dermally applied microarray
- Drug delivery
- Headache
- Intracutaneous
- Migraine
- Triptan
- Zolmitriptan
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
Cite this
Use of Most Bothersome Symptom as a Coprimary Endpoint in Migraine Clinical Trials : A Post-Hoc Analysis of the Pivotal ZOTRIP Randomized, Controlled Trial. / Dodick, David William; Tepper, Stewart J.; Friedman, Deborah I.; Gelfand, Amy A.; Kellerman, Donald J.; Schmidt, Peter C.
In: Headache, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Use of Most Bothersome Symptom as a Coprimary Endpoint in Migraine Clinical Trials
T2 - A Post-Hoc Analysis of the Pivotal ZOTRIP Randomized, Controlled Trial
AU - Dodick, David William
AU - Tepper, Stewart J.
AU - Friedman, Deborah I.
AU - Gelfand, Amy A.
AU - Kellerman, Donald J.
AU - Schmidt, Peter C.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Objective: To better understand the utility of using pain freedom and most bothersome headache-associated symptom (MBS) freedom as co-primary endpoints in clinical trials of acute migraine interventions. Background: Adhesive dermally applied microarray (ADAM) is an investigational system for intracutaneous drug administration. The recently completed pivotal Phase 2b/3 study (ZOTRIP), evaluating ADAM zolmitriptan for the treatment of acute moderate to severe migraine, was one of the first large studies to incorporate MBS freedom and pain freedom as co-primary endpoints per recently issued guidance by the US Food and Drug Administration. In this trial, the proportion of patients treated with ADAM zolmitriptan 3.8 mg, who were pain-free and MBS-free at 2 hours post-dose, was significantly higher than for placebo. Methods: We undertook a post-hoc analysis of data from the ZOTRIP trial to examine how the outcomes from this trial compare to what might have been achieved using the conventional co-primary endpoints of pain relief, nausea, photophobia, and phonophobia. Results: Of the 159 patients treated with ADAM zolmitriptan 3.8 mg or placebo, prospectively designated MBS were photophobia (n=79), phonophobia (n=43), and nausea (n=37). Two-hour pain free rates in those with photophobia as the MBS were 36% for ADAM zolmitriptan 3.8 mg and 14% for placebo (P=.02). Corresponding rates for those with phonophobia as the MBS were 14% and 41% (P=.05). For those whose MBS was nausea, corresponding values were 56% and 16%, respectively (P=.01). Two-hour freedom from the MBS for active drug vs placebo were 67% vs 35% (P<.01) for photophobia, 55% vs 43% (P=.45) for phonophobia, and 89% vs 58% for nausea (P=.04). MBS freedom but not pain freedom was achieved in 28%. Only 1 patient (1%) achieved pain freedom, but not MBS freedom. The proportion with both pain and MBS freedom was highest (56%) among those whose MBS was nausea. Conclusion: In this study, the use of MBS was feasible and seemed to compare favorably to the previously required 4 co-primary endpoints.
AB - Objective: To better understand the utility of using pain freedom and most bothersome headache-associated symptom (MBS) freedom as co-primary endpoints in clinical trials of acute migraine interventions. Background: Adhesive dermally applied microarray (ADAM) is an investigational system for intracutaneous drug administration. The recently completed pivotal Phase 2b/3 study (ZOTRIP), evaluating ADAM zolmitriptan for the treatment of acute moderate to severe migraine, was one of the first large studies to incorporate MBS freedom and pain freedom as co-primary endpoints per recently issued guidance by the US Food and Drug Administration. In this trial, the proportion of patients treated with ADAM zolmitriptan 3.8 mg, who were pain-free and MBS-free at 2 hours post-dose, was significantly higher than for placebo. Methods: We undertook a post-hoc analysis of data from the ZOTRIP trial to examine how the outcomes from this trial compare to what might have been achieved using the conventional co-primary endpoints of pain relief, nausea, photophobia, and phonophobia. Results: Of the 159 patients treated with ADAM zolmitriptan 3.8 mg or placebo, prospectively designated MBS were photophobia (n=79), phonophobia (n=43), and nausea (n=37). Two-hour pain free rates in those with photophobia as the MBS were 36% for ADAM zolmitriptan 3.8 mg and 14% for placebo (P=.02). Corresponding rates for those with phonophobia as the MBS were 14% and 41% (P=.05). For those whose MBS was nausea, corresponding values were 56% and 16%, respectively (P=.01). Two-hour freedom from the MBS for active drug vs placebo were 67% vs 35% (P<.01) for photophobia, 55% vs 43% (P=.45) for phonophobia, and 89% vs 58% for nausea (P=.04). MBS freedom but not pain freedom was achieved in 28%. Only 1 patient (1%) achieved pain freedom, but not MBS freedom. The proportion with both pain and MBS freedom was highest (56%) among those whose MBS was nausea. Conclusion: In this study, the use of MBS was feasible and seemed to compare favorably to the previously required 4 co-primary endpoints.
KW - Adhesive dermally applied microarray
KW - Drug delivery
KW - Headache
KW - Intracutaneous
KW - Migraine
KW - Triptan
KW - Zolmitriptan
UR - http://www.scopus.com/inward/record.url?scp=85047637736&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047637736&partnerID=8YFLogxK
U2 - 10.1111/head.13327
DO - 10.1111/head.13327
M3 - Article
JO - Headache
JF - Headache
SN - 0017-8748
ER -