title: A Phase I, Open-Label, Single-Dose Safety, Pharmacokinetic, and Tolerability Study of the Sumatriptan Iontophoretic Transdermal System in Adolescent Migraine Patients.
abstract: OBJECTIVE
  To evaluate the safety, tolerability, and pharmacokinetics of sumatriptan delivered by the iontophoretic transdermal system (TDS) in adolescent patients.
  
  
  BACKGROUND
  Since nausea can be a prominent and early symptom of migraine, nonoral treatment options are often required. Sumatriptan iontophoretic TDS is approved for the acute treatment of migraine in adults. The present study evaluates the pharmacokinetics of sumatriptan administered via the iontophoretic TDS in adolescents, contrasting the findings with historical data from adults.
  
  
  METHODS
  Patients aged 12-17 years (inclusive) with acute migraine were treated with sumatriptan iontophoretic TDS for 4 hours. Blood samples for pharmacokinetic profiling of sumatriptan were obtained prior to dosing and at predetermined time points covering the 12 hours postonset of treatment. Key pharmacokinetic endpoints included Cmax (peak plasma drug concentration), tmax (time to Cmax ), AUC0-∞ (area under the plasma concentration-time curve from time 0 to infinity), and t½ (terminal elimination half-life). Safety was evaluated by monitoring of adverse events in addition to laboratory and clinical assessments.
  
  
  RESULTS
  The sample consisted of 37 patients, and 36 were included in the PK evaluable population. Cmax , tmax , AUC0-∞ , and t½ values were all similar between male and female patients and between younger (12-14 years) and older (15-17 years) adolescents. When compared with historical adult data, adolescent patients demonstrated similar systemic exposures to those observed in adults (mean Cmax 20.20 (±6.43) ng/mL in adolescents vs 21.89 (±6.15) ng/mL in adults; mean AUC0-∞ 98.1 (±28.1) ng·h/mL in adolescents vs 109.7 (±26.1) ng·h/mL in adults). All adverse events were mild or moderate, with application-site paresthesia being the most common (32%). No clinically relevant changes in laboratory values, vital signs, or electrocardiogram findings were observed.
  
  
  CONCLUSIONS
  The iontophoretic TDS produced mean systemic exposures to sumatriptan in younger and older adolescents, in line with what was seen in adult subjects. It was generally well tolerated.
authors.affiliation: Research and Development, Teva Pharmaceutical Industries, Netanya, Israel.
authors.forename: Dikla
authors.initials: D
authors.lastname: Gutman
authors.affiliation: Research and Development, Teva Pharmaceutical Industries, West Chester, PA, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Hellriegel
authors.affiliation: Clinical Development, Teva Pharmaceutical Industries, Frazer, PA, USA.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Aycardi
authors.affiliation: Clinical Development, Teva Pharmaceutical Industries, Frazer, PA, USA.
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Bigal
authors.affiliation: Research and Development, Teva Pharmaceutical Industries, West Chester, PA, USA.
authors.forename: Jeevan
authors.initials: J
authors.lastname: Kunta
authors.affiliation: Clinical Development, Teva Pharmaceutical Industries, Frazer, PA, USA.
authors.forename: Rohini
authors.initials: R
authors.lastname: Chitra
authors.affiliation: Children's Health Center, Duke University Medical Center, Durham, NC, USA.
authors.forename: Sujay
authors.initials: S
authors.lastname: Kansagra
authors.affiliation: Research and Development, Teva Pharmaceutical Industries, Netanya, Israel.
authors.forename: Orna Srur
authors.initials: OS
authors.lastname: Kidron
authors.affiliation: Patient Safety & Pharmacovigilance, Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Helena
authors.initials: H
authors.lastname: Knebel
authors.affiliation: Dallas Pediatric Neurology Associates, Dallas, TX, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Linder
authors.affiliation: Clinical Development, Teva Pharmaceutical Industries, Frazer, PA, USA.
authors.forename: Yuju
authors.initials: Y
authors.lastname: Ma
authors.affiliation: NuPathe Inc, Conshohocken, PA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Pierce
authors.affiliation: Palm Beach Neurology - Premiere Research Institute, West Palm Beach, FL, USA.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Winner
authors.affiliation: Research and Development, Teva Pharmaceutical Industries, Netanya, Israel. Ofer.Spiegelstein@teva.co.il.
authors.forename: Ofer
authors.initials: O
authors.lastname: Spiegelstein
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007478:Iontophoresis / Q000009:adverse effects / Q000379:methods; D008297:Male; D008881:Migraine Disorders / Q000097:blood / Q000188:drug therapy*; D018170:Sumatriptan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D014662:Vasoconstrictor Agents; D018170:Sumatriptan
keywords: Zecuity; adolescents; iontophoretic transdermal system; migraine; pharmacokinetics; sumatriptan