title: Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations.
abstract: OBJECTIVE
  Rotigotine transdermal patch is approved for the treatment of early and advanced idiopathic Parkinson's disease (PD) and moderate-to-severe idiopathic restless legs syndrome (RLS). A cold chain manufacturing and distribution process was temporarily implemented in 2008, as this reduced the crystal formation reported within patches stored at room temperature. In order to overcome the crystallization issue and meet EMA and FDA requirements, a new room temperature stable formulation was developed. The three studies reported here were conducted to determine whether the new room temperature stable patch demonstrated similar bioavailability and adhesiveness to the original and intermediate patches.
  
  
  METHODS
  Data are reported from three cross-over studies that compared the original, cold chain and room temperature stable patch. Two open-label bioequivalence studies investigated the 2 mg/24 h dosage in healthy individuals (SP951, n = 52 [Clinicaltrials.gov: NCT00881894]; SP0987, n = 50 [NCT01059903]) and a double-blind patch adhesiveness study investigated the 8 mg/24 h dosage in patients with PD (SP1066, n = 56 [NCT01338896]).
  
  
  RESULTS
  Plasma concentration-time curves and geometric means for pharmacokinetic parameters were similar for the cold chain vs. original patch in SP951 (AUC(0-tz): 2.68 vs. 2.71 ng/mL*h; point estimate: 0.99 [90% confidence interval (CI): 0.91, 1.07]) (Cmax: 0.131 vs. 0.136 ng/mL; 0.96 [0.89, 1.04]) and for the room temperature stable vs. cold chain patch in SP0987 (AUC(0-tz): 4.51 vs. 4.87 ng/mL*h; 0.90 [0.84, 0.97]) (Cmax: 0.23 vs. 0.23 ng/mL; 0.95 [0.88, 1.02]). In both studies, 90% CIs for ratios of AUC(0-tz) and Cmax were within the bioequivalence acceptance range (0.8-1.25). In SP1066, overall median adhesiveness scores were similar for cold chain (0.5 [range: 0-4]) and room temperature stable (0 [0-4]) formulations.
  
  
  CONCLUSIONS
  These results demonstrated bioequivalence and indicated similar adhesiveness of the approved room temperature stable rotigotine patch with the original and cold chain patches. Potential limitations include the enrolment of healthy volunteers in the bioequivalence studies, as these individuals were likely to be younger than the general PD or RLS population.
authors.affiliation: UCB Pharma , Monheim am Rhein , Germany.
authors.forename: Jan-Peer
authors.initials: JP
authors.lastname: Elshoff
authors.forename: Lars
authors.initials: L
authors.lastname: Timmermann
authors.forename: Miriam
authors.initials: M
authors.lastname: Schmid
authors.forename: Christoph
authors.initials: C
authors.lastname: Arth
authors.forename: Michael
authors.initials: M
authors.lastname: Komenda
authors.forename: Marcus
authors.initials: M
authors.lastname: Brunnert
authors.forename: Lars
authors.initials: L
authors.lastname: Bauer
mesh_terms: D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy; D012148:Restless Legs Syndrome / Q000097:blood / Q000188:drug therapy; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D057968:Transdermal Patch
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine