Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study

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Abstract

OBJECTIVE: To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI).

DESIGN: Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden.

METHODS: Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires.

RESULTS: Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008).

CONCLUSIONS: In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.

Detaljer

Författare
  • Anna G. Nilsson
  • Ragnhildur Bergthorsdottir
  • Pia Burman
  • Per Dahlqvist
  • Bertil Ekman
  • Britt Edén Engström
  • Oskar Ragnarsson
  • Stanko Skrtic
  • Jeanette Wahlberg
  • Heinrich Achenbach
  • Sharif Uddin
  • Claudio Marelli
  • Gudmundur Johannsson
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
  • Göteborgs universitet
  • Umeå University
  • Linköping University
  • Uppsala University Hospital
  • Shire International GmbH
  • Shire
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes
Originalspråkengelska
Sidor (från-till)715-725
Antal sidor11
TidskriftEuropean Journal of Endocrinology
Volym176
Utgivningsnummer6
StatusPublished - 2017
PublikationskategoriForskning
Peer review utfördJa