title: Bioequivalence and adhesion evaluation of transdermal clonidine following a change in excipient supplier.
abstract: OBJECTIVE
  To evaluate the bioequivalence (BE), safety, tolerability, and adhesion of Oppanol® polyisobutylene (PIB)-containing transdermal therapeutic system (TTS) formulation (test treatment, T) with VistanexTM PIB-containing TTS formulation (reference treatment, R) of clonidine.
  
  
  METHODS
  This randomized, double-blind, 2-way crossover study comprised a 7-day treatment with 0.3 mg clonidine/24 h (T1/R1), a 7-day washout, and another 7-day treatment (R1/T1) period. After a 3-day washout period, subjects used T2 and R2 (each 0.1 mg clonidine/24 h) simultaneously in the 7-day adhesion phase. Primary endpoints were AUC0-168 and Cavg. Secondary endpoints were AUC0-∞ and Cmax. Additional endpoints included adhesion properties for all phases. For the primary endpoint, the geometric mean (gMean) ratios for test/reference treatment were calculated with BE defined as 90% confidence interval (CI) between 80 and 125%.
  
  
  RESULTS
  58 subjects (mean age, 41.3 years) received treatment (T1/R1, n = 29; R1/T1, n = 29); 55 completed the adhesion phase. BE criteria were met for the primary and secondary endpoints. Adjusted gMean ratios for T1/R1 were 102.3% (90% CI: 95.7%, 109.4%) for AUC0-168; 104.3% (90% CI: 98.4%, 110.5%) for Cavg; 102.8% (90% CI: 97.3%, 108.6%) for AUC0-∞; and 104.0% (90% CI: 98.2%, 110.3%) for Cmax. Mean adhesion was greater than 90% for all four patch types when data from all assessment times were included. Most frequently reported adverse events were general disorders and local irritation.
  
  
  CONCLUSIONS
  Clonidine Oppanol® PIB-containing TTS formulation was bioequivalent to VistanexTM PIB-containing TTS formulation and had similar adhesive properties. Both doses and formulations of clonidine-TTS were well tolerated.
authors.forename: Jerome
authors.initials: J
authors.lastname: Ehrlich
authors.forename: Bonnie
authors.initials: B
authors.lastname: Beck
authors.forename: Ralf
authors.initials: R
authors.lastname: Thiedmann
authors.forename: Kristell
authors.initials: K
authors.lastname: Marzin
authors.forename: Thomas
authors.initials: T
authors.lastname: MacGregor
mesh_terms: D000268:Adhesiveness; D000279:Administration, Cutaneous; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D003000:Clonidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011090:Polyenes / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013810:Therapeutic Equivalency; D057968:Transdermal Patch
chemical_list: D000959:Antihypertensive Agents; D005079:Excipients; D011090:Polyenes; D011108:Polymers; C008967:polyisobutylene; D003000:Clonidine