Effects of a Supratherapeutic Dose of Investigational Orally Inhaled Dihydroergotamine (MAP0004) on QT Interval: A Randomized, Double-Blind, Active- and Placebo-Controlled Crossover Study in Healthy Volunteers

Clinical Therapeutics

Volumn 34, Issue 9, 2012, Pages 1920-1928

  Kori, Shashidhar ^a   Kellerman, Donald J ^a   Voloshko, Polina ^b   Haugen, Gregory ^c  

^a MAP Pharmaceuticals Inc   (United States)

^b Cardiocore   (United States)

^c Cetero Research   (United States)

Author keywords

Dihydroergotamine; MAP0004; Moxifloxacin; Thorough QT interval

Indexed keywords

DIHYDROERGOTAMINE; MAP0004; MOXIFLOXACIN; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; BACKACHE; CONTACT DERMATITIS; CONTROLLED STUDY; COUGHING; DIARRHEA; DIZZINESS; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG INDUCED HEADACHE; DRUG TOLERABILITY; DYSMENORRHEA; ELECTROCARDIOGRAM; FEMALE; HUMAN; HUMAN EXPERIMENT; LIMB PAIN; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NORMAL HUMAN; PARESTHESIA; QT INTERVAL; TIME TO MAXIMUM PLASMA CONCENTRATION; VOMITING;

ADMINISTRATION, INHALATION; ADULT; AZA COMPOUNDS; CROSS-OVER STUDIES; DIHYDROERGOTAMINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; ELECTROCARDIOGRAPHY; FEMALE; HUMANS; LONG QT SYNDROME; MALE; MIDDLE AGED; QUINOLINES; VASOCONSTRICTOR AGENTS; YOUNG ADULT;

EID: 84866165263     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2012.08.001     Document Type: Article

References (14)

1. Silberstein S.D., McCrory D.C. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Headache 2003, 43:144-166.
2. Velentgas P., Cole J.A., Mo J., et al. Severe vascular events in migraine patients. Headache 2004, 44:642-651.
3. Wammes-van der Heijden E.A., Rahimtoola H., Leufkens H.G., et al. Risk of ischemic complications related to the intensity of triptan and ergotamine use. Neurology 2006, 67:1128-1134.
4. Guidance for Industry. E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Arrhythmic Drugs 2005, US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research.
5. Baron E.P., Tepper S.J. Orally inhaled dihydroergotamine. Future Neurol 2011, 6:327-333.
6. Aurora S.K., Rozen T.D., Kori S., Shrewsbury S.B. A randomized, double blind, placebo controlled study of MAP0004 in adult patients with migraine. Headache 2009, 49:826-837.
7. Aurora S.K., Silberstein S.D., Kori S.H., et al. MAP0004, orally inhaled DHE: a randomized, controlled study in the acute treatment of migraine. Headache 2011, 51:507-517.
8. Shrewsbury S.B., Stonerook M., Okikawa J.K. Intrapulmonary and intravenous administrations of dihydroergotamine mesylate (DHE) have similar cardiovascular effects in the conscious dog. Br J Pharmacol 2008, 154:1254-1265.
9. Berenberg E., Clemons D., Kellerman D., et al. A randomized, double-blind, placebo-controlled, three-period crossover study comparing the acute effects of LEVADEX (MAP0004, orally inhaled DHE) and intravenous DHE on pulmonary arterial systolic pressure. Headache 2011, 51:23.
10. Stovner L.j., Hagen K., Jensen R., et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia 2007, 27:193-210.
11. Shrewsbury S.B., Cook R.O., Taylor G., et al. Safety and pharmacokinetics of dihydroergotamine mesylate administered via a novel (Tempo) inhaler. Headache 2008, 48:355-367.
12. Shrewsbury S.B., Kori S., Miller S.D., et al. Randomized, double blind, placebo controlled study of the safety, tolerability and pharmacokinetics of MAP0004 (orally-inhaled DHE) in adult asthmatics. Curr Med Res Opin 2008, 24:1977-1985.
13. Forst A., Febbraro S., Kellerman D., et al. An open-label, two-period crossover study comparing the pharmacokinetics and tolerability of LEVADEX (MAP0004, orally inhaled DHE) and intravenous DHE (DHE45®) in smoking and non-smoking adult volunteers. Headache 2011, 51(Suppl 1):17. Abstract P31.
14. Armer T.A., Lynch M., Moutvic R., Singer A. Toxicological assessment of dihydroergotamine after chronic inhalation in dogs. Toxicol Pathol 2011, 39:544-552.