Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE®-PK) in healthy subjects

Expert Opin Investig Drugs. 2016 Dec;25(12):1361-1370. doi: 10.1080/13543784.2016.1255724.


Background: This Phase I study (VOLTAIRE®-PK) aimed to evaluate three-way pharmacokinetic similarity (bioequivalence), safety, and immunogenicity of BI 695501 (a Humira® [adalimumab] biosimilar candidate) compared with US- and EU-approved Humira in healthy male subjects.

Methods: Subjects (N = 327) were randomized 1:1:1 to receive one 40-mg subcutaneous dose of BI 695501, US- or EU-approved Humira; safety was assessed for 70 days. Bioequivalence was evaluated using the average bioequivalence method to test if the 90% confidence intervals (CIs) of the geometric means (BI 695501 vs US- and EU-approved Humira) for the primary end points were within prespecified acceptance ranges (80-125%). Immunogenicity was assessed using a sensitive bridging method.

Results: Bioequivalence between BI 695501 and US- and EU-approved Humira was demonstrated with the 90% CIs of the ratios of all primary end points: Cmax, AUC0-inf, pred and AUC0-tz being within the prespecified acceptance ranges of 80-125%. Concentration vs time profiles were similar as were the time course and frequency of immunogenic responses. All study drugs showed similar safety and tolerability results.

Conclusions: Three-way bioequivalence of BI 695501 to US- and EU-approved Humira was demonstrated; safety and immunogenicity results of the three study drugs were also similar.

Clinical trial registration: 2013-003722-84 (EudraCT) and NCT02045979.

Keywords: Adalimumab; BI 695501; Humira; bioequivalence; biosimilar; pharmacokinetics.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adalimumab / administration & dosage*
  • Adalimumab / adverse effects
  • Adalimumab / metabolism
  • Adult
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacokinetics
  • Area Under Curve
  • Biosimilar Pharmaceuticals / administration & dosage*
  • Biosimilar Pharmaceuticals / adverse effects
  • Biosimilar Pharmaceuticals / pharmacokinetics
  • Double-Blind Method
  • Humans
  • Male
  • Therapeutic Equivalency
  • Young Adult


  • Antirheumatic Agents
  • Biosimilar Pharmaceuticals
  • Adalimumab

Associated data