title: [Assessment of the efficacy, safety and pharmacokinetics of SKG-02 (recombinant human TSH) in postoperative diagnosis of well-differentiated thyroid cancer--a Japanese prospective, controlled, multicenter open-label study].
abstract: OBJECTIVE
  This study sought to assess the safety, efficacy, impact on hypothyroid symptoms, and pharmacokinetics of SKG-02 (rhTSH, thyrotropin alfa) in the diagnostic follow-up of Japanese patients with well-differentiated thyroid carcinoma (WDTC).
  
  
  METHODS
  Ten Japanese adults with WDTC were enrolled into a prospective, multicenter, open-label trial comparing diagnostic whole-body scintigraphy (dxWBS) and serum thyroglobulin (Tg) testing aided by SKG-02 versus these procedures aided by thyroid hormone withdrawal (THW). Patients were their own controls. Variables compared included scan set ability to detect radioiodine uptake by remnant or malignant thyroid tissue, scan set quality, diagnostic sensitivity of dxWBS and Tg testing alone or combined, frequency of hypothyroid signs/symptoms, and adverse events (AEs). SKG-02 pharmacokinetic variables including maximum concentration (Cmax), time to Cmax (Tmax) and the area under the time-concentration curve (AUC) were calculated.
  
  
  RESULTS
  In a blinded evaluation by an independent committee of 3 nuclear medicine experts, 70% of SKG-02 dxWBS scan sets were rated "equivalent" (n = 7) or "superior" (n = 0) to their THW counterparts in ability to detect radioiodine uptake in healthy or malignant thyroid tissue. Therefore the study exceeded its primary endpoint of a 60% equivalence/superiority rate. SKG-02 Tg testing identified 3/3 cases of disease. Hypothyroid signs/symptoms were substantially more frequent during THW than during euthyroidism permitted by SKG-02 use. SKG-02 was well-tolerated, with no severe or serious drug-related AEs. Cmax was 240.8 +/- 65.9 microIU/ml, Tmax was 28.75 +/- 14.21 hr after the first SKG-02 injection, and AUC was 11,414 +/- 3,462 microIU hr/ml in 9 patients evaluable for pharmacokinetics.
  
  
  CONCLUSIONS
  SKG-02 was safe and effective in the diagnostic follow-up of Japanese patients with WDTC, avoiding hypothyroid morbidity relative to THW. These and the pharmacokinetic findings were similar to those of overseas Phase III studies.
authors.affiliation: Sugita Genpaku Memorial Obama Municipal Hospital.
authors.forename: Junji
authors.initials: J
authors.lastname: Konishi
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Nakada
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kusakabe
authors.forename: Masako
authors.initials: M
authors.lastname: Maki
authors.forename: Masako
authors.initials: M
authors.lastname: Kanbe
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Higashi
authors.forename: Keigo
authors.initials: K
authors.lastname: Endo
authors.forename: Katsuji
authors.initials: K
authors.lastname: Ikekubo
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kubo
authors.forename: Naofumi
authors.initials: N
authors.lastname: Ishikawa
mesh_terms: D000368:Aged; D044466:Asian People; D002277:Carcinoma / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D011877:Radionuclide Imaging; D013954:Thyroglobulin / Q000097:blood; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging*; D013965:Thyroidectomy; D057073:Thyrotropin Alfa / Q000493:pharmacokinetics / Q000494:pharmacology*; D051598:Whole Body Imaging
chemical_list: D007457:Iodine Radioisotopes; D057073:Thyrotropin Alfa; D013954:Thyroglobulin