PMID- 38413540
OWN - NLM
STAT- MEDLINE
DCOM- 20240321
LR  - 20240401
IS  - 1526-4610 (Electronic)
IS  - 0017-8748 (Linking)
VI  - 64
IP  - 3
DP  - 2024 Mar
TI  - A randomized, open-label, 5-period crossover study evaluating the 
      pharmacokinetics and safety of a single dose of intranasal dihydroergotamine 
      (DHE) powder (STS101), intramuscular DHE mesylate, and liquid nasal spray DHE in 
      healthy adults.
PG  - 266-275
LID - 10.1111/head.14685 [doi]
AB  - OBJECTIVE: To compare the safety and pharmacokinetics (PK) of dihydroergotamine 
      (DHE) after administration of intranasal DHE powder (STS101), liquid nasal spray 
      (LNS) DHE mesylate, and intramuscular (IM) DHE mesylate injection in healthy 
      participants. BACKGROUND: DHE is an effective acute migraine treatment; however, 
      self-administration difficulties have prevented its broader role in the 
      management of migraine. METHODS: This randomized, active-controlled, five-period 
      crossover study was conducted over 5 weeks separated by 1-week washout periods. 
      Three STS101 dosage strengths (5.2, 7.0, 8.6 mg), and one dose each of LNS DHE 
      2.0 mg, and IM DHE 1.0 mg, were administered to 36 healthy participants. Liquid 
      chromatography, tandem mass spectrometry was used to determine DHE (including its 
      8'OH-DHE metabolite) plasma levels and to calculate PK parameters (C(max) , 
      T(max) , AUC(0-2h) , AUC(0-last) , AUC(0-inf) , and t(1/2) ). Safety was 
      evaluated by monitoring adverse events (AEs), vital signs, electrocardiograms, 
      nasal examinations, and laboratory parameters. RESULTS: Thirty-six participants 
      (mean age 36 years; 19% Hispanic Black and 81% Hispanic White) were enrolled. DHE 
      plasma concentrations rose rapidly after STS101 5.2, 7.0, and 8.6 mg and IM DHE 
      injection, with mean concentrations greater than 2000 pg/mL for all STS101 dose 
      strengths at 20 min. All STS101 dose strengths showed approximately 3-fold higher 
      C(max) , AUC(0-2h) , and AUC(0-inf) , than the LNS DHE. The mean AUC(0-inf) of 
      STS101 7.0 and 8.6 mg were comparable to IM DHE (12,600 and 13,200 vs. 13,400 h x 
      pg/mL). All STS101 dose strengths showed substantially lower variability (CV%) 
      compared to LNS DHE for C(max) (35%-41% vs. 87%), and AUC(0-inf) (37%-46% vs. 
      65%). STS101 was well tolerated, and all treatment-emergent AEs were mild and 
      transient. CONCLUSION: STS101 showed rapid absorption and was well tolerated with 
      mild and transient treatment-emergent AEs. Achieving effective DHE plasma 
      concentrations within 10 min, STS101 displayed a favorable PK profile relative to 
      the LNS with higher C(max) , AUC(0-2h) , and AUC(0inf) , and with greater 
      response consistency. The AUC(0-inf) was comparable to IM DHE.
CI  - (c) 2024 Satsuma Pharmaceuticals. Headache: The Journal of Head and Face Pain 
      published by Wiley Periodicals LLC on behalf of American Headache Society.
FAU - Lipton, Richard B
AU  - Lipton RB
AUID- ORCID: 0000-0003-2652-2897
AD  - Department of Neurology Montefiore Headache Center, Albert Einstein College of 
      Medicine, Bronx, New York, USA.
FAU - Albrecht, Detlef
AU  - Albrecht D
AD  - Satsuma Pharmaceuticals Inc., Durham, North Carolina, USA.
FAU - Bermudez, Maria
AU  - Bermudez M
AD  - Quotient Sciences, Miami, Florida, USA.
FAU - Hu, Jerry
AU  - Hu J
AD  - Allucent, Gary, North Carolina, USA.
FAU - Hussey, Elizabeth
AU  - Hussey E
AD  - Allucent, Gary, North Carolina, USA.
FAU - Levy, Jeff
AU  - Levy J
AD  - Quotient Sciences, Miami, Florida, USA.
LA  - eng
GR  - Satsuma Pharmaceuticals, Inc/
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20240227
PL  - United States
TA  - Headache
JT  - Headache
JID - 2985091R
RN  - 436O5HM03C (Dihydroergotamine)
RN  - 0 (Mesylates)
RN  - 0 (Nasal Sprays)
RN  - 0 (Powders)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Cross-Over Studies
MH  - *Dihydroergotamine
MH  - *Mesylates/adverse effects
MH  - *Migraine Disorders/drug therapy
MH  - Nasal Sprays
MH  - Powders
OTO - NOTNLM
OT  - DHE
OT  - dihydroergotamine mesylate
OT  - intranasal
OT  - migraine
OT  - pharmacokinetics
EDAT- 2024/02/28 00:43
MHDA- 2024/03/21 12:42
CRDT- 2024/02/27 23:19
PHST- 2023/12/19 00:00 [revised]
PHST- 2023/10/18 00:00 [received]
PHST- 2023/12/21 00:00 [accepted]
PHST- 2024/03/21 12:42 [medline]
PHST- 2024/02/28 00:43 [pubmed]
PHST- 2024/02/27 23:19 [entrez]
AID - 10.1111/head.14685 [doi]
PST - ppublish
SO  - Headache. 2024 Mar;64(3):266-275. doi: 10.1111/head.14685. Epub 2024 Feb 27.