title: Longitudinal Modeling of the Relationship Between Mean Plasma Glucose and HbA1c Following Antidiabetic Treatments.
abstract: Late-phase clinical trials within diabetes generally have a duration of 12-24 weeks, where 12 weeks may be too short to reach steady-state glycated hemoglobin (HbA1c). The main determinant for HbA1c is blood glucose, which reaches steady state much sooner. In spite of this, few publications have used individual data to assess the time course of both glucose and HbA1c, for predicting HbA1c. In this paper, we present an approach for predicting HbA1c at end-of-trial (24-28 weeks) using glucose and HbA1c measurements up to 12 weeks. The approach was evaluated using data from 4 trials covering 12 treatment arms (oral antidiabetic drug, glucagon-like peptide-1, and insulin treatment) with measurements at 24-28 weeks to evaluate predictions vs. observations. HbA1c percentage was predicted for each arm at end-of-trial with a mean prediction error of 0.14% [0.01;0.24]. Furthermore, end points in terms of HbA1c reductions relative to comparator were accurately predicted. The proposed model provides a good basis to optimize late-stage clinical development within diabetes.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e82; doi:10.1038/psp.2013.58; advance online publication 30 October 2013.
authors.affiliation: Quantitative Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: J B
authors.initials: JB
authors.lastname: Møller
authors.forename: R V
authors.initials: RV
authors.lastname: Overgaard
authors.forename: M C
authors.initials: MC
authors.lastname: Kjellsson
authors.forename: N R
authors.initials: NR
authors.lastname: Kristensen
authors.forename: S
authors.initials: S
authors.lastname: Klim
authors.forename: S H
authors.initials: SH
authors.lastname: Ingwersen
authors.forename: M O
authors.initials: MO
authors.lastname: Karlsson