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\begin{document}

\title{Safety, tolerability and pharmacokinetic characterisation of DACRA
KBP-042 in healthy male subjects}



\author[1]{Kim Henriksen}%
\author[2]{Karen Broekhuizen }%
\author[2]{Wadim  de Boon}%
\author[1]{Morten Karsdal}%
\author[3]{Asger Bihlet}%
\author[1]{Claus Christiansen}%
\author[2]{Marlous Dillingh}%
\author[2]{Marieke de Kam}%
\author[4]{Raj Kumar}%
\author[2]{Jacobus Burggraaf}%
\author[5]{Ingrid Kamerling}%
\affil[1]{Nordic Bioscience}%
\affil[2]{Centre for Human Drug Research}%
\affil[3]{Nordic Bioscience A/S}%
\affil[4]{KeyBioscience AG}%
\affil[5]{CHDR}%


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  \date{May 25, 2024}


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\begin{abstract}
There is a need for anti-diabetic agents successfully targeting insulin
sensitivity and treating obesity control at the same time. The aim of
this first-in-human study was 1) to evaluate safety and tolerability; 2)
to evaluate pharmacokinetics and 3) to assess indications of receptor
engagement of single ascending doses of KBP-042, a Dual Amylin and
Calcitonin Receptor Agonists (DACRA) that has shown promising
preclinical data, with superior activity in terms of typical
amylin-induced responses including reduction of food intake, weight loss
and gluco-regulatory capacities. A randomised double-blind
placebo-controlled single ascending dose study was performed with six
dose levels of KBP-042 (5, 7.5, 10, 20, 20 evening and 40\selectlanguage{greek}µ\selectlanguage{english}g) in healthy
male adults. KBP-042 or placebo was administered as a single dose after
an overnight fast, followed by a standardized lunch after four hours.
KBP-042 was associated with dose-dependent complaints of nausea and
vomiting, with a lack of tolerability at doses of 20\selectlanguage{greek}µ\selectlanguage{english}g and above. Doses
of 5 to 40 \selectlanguage{greek}μ\selectlanguage{english}g KBP-042 were behaved according to a linear pharmacokinetic
profile. Indications of target receptor engagement were observed at the
level of glucose control and lowering of bone resorption, compared to
placebo. The results of this study showed that doses up to 40 \selectlanguage{greek}μ\selectlanguage{english}g were
safe, although tolerability was not present at the highest doses. The
study confirmed target receptor engagement at the studied doses.%
\end{abstract}%



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