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Safety, tolerability and pharmacokinetic characterisation of DACRA KBP-042 in healthy male subjects
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  • Kim Henriksen,
  • Karen Broekhuizen ,
  • Wadim de Boon,
  • Morten Karsdal,
  • Asger Bihlet,
  • Claus Christiansen,
  • Marlous Dillingh,
  • Marieke de Kam,
  • Raj Kumar,
  • Jacobus Burggraaf,
  • Ingrid Kamerling
Kim Henriksen
Nordic Bioscience
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Karen Broekhuizen
Centre for Human Drug Research
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Wadim de Boon
Centre for Human Drug Research
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Morten Karsdal
Nordic Bioscience
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Asger Bihlet
Nordic Bioscience A/S
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Claus Christiansen
Nordic Bioscience
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Marlous Dillingh
Centre for Human Drug Research
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Marieke de Kam
Centre for Human Drug Research
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Raj Kumar
KeyBioscience AG
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Jacobus Burggraaf
Centre for Human Drug Research
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Ingrid Kamerling
CHDR
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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 40µg) 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 20µg and above. Doses of 5 to 40 μg 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 μg were safe, although tolerability was not present at the highest doses. The study confirmed target receptor engagement at the studied doses.

Peer review status:ACCEPTED

09 Feb 2021Submitted to British Journal of Clinical Pharmacology
10 Feb 2021Submission Checks Completed
10 Feb 2021Assigned to Editor
13 Feb 2021Reviewer(s) Assigned
02 Mar 2021Review(s) Completed, Editorial Evaluation Pending
06 Mar 2021Editorial Decision: Revise Major
28 Apr 20211st Revision Received
29 Apr 2021Submission Checks Completed
29 Apr 2021Assigned to Editor
29 Apr 2021Review(s) Completed, Editorial Evaluation Pending
01 May 2021Reviewer(s) Assigned
08 May 2021Editorial Decision: Accept