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.
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, predand AUC0-tzbeing 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.


BACKGROUND
2013-003722-84 (EudraCT) and NCT02045979.
a Christchurch Clinical Studies Trust , Christchurch , New Zealand.
Christopher
C
Wynne
b Boehringer Ingelheim , Ingelheim , Germany.
Mario
M
Altendorfer
b Boehringer Ingelheim , Ingelheim , Germany.
Ivo
I
Sonderegger
c SGS, Clinical Pharmacology Unit , Antwerp , Belgium.
Lien
L
Gheyle
d Auckland Clinical Studies Limited , Auckland , New Zealand.
Rod
R
Ellis-Pegler
b Boehringer Ingelheim , Ingelheim , Germany.
Susanne
S
Buschke
b Boehringer Ingelheim , Ingelheim , Germany.
Benjamin
B
Lang
b Boehringer Ingelheim , Ingelheim , Germany.
Deepak
D
Assudani
b Boehringer Ingelheim , Ingelheim , Germany.
Sandeep
S
Athalye
b Boehringer Ingelheim , Ingelheim , Germany.
Niklas
N
Czeloth
D000068879:Adalimumab / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency; D055815:Young Adult
D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D000068879:Adalimumab
Adalimumab; BI 695501; Humira; bioequivalence; biosimilar; pharmacokinetics