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Clinical Trial
. 2020 Oct;127(4):329-337.
doi: 10.1111/bcpt.13466. Epub 2020 Jul 23.

Four phase 1 trials to evaluate the safety and pharmacokinetic profile of single and repeated dosing of SCO-101 in adult male and female volunteers

Troels K Bergmann  1   2   3 , Tore B Stage  1 , Jan Stenvang  4   5 , Palle Christophersen  6 , Thomas A Jacobsen  6 , Nicklas L Roest  4 , Peter M Vestlev  4 , Nils Brünner  4
Affiliations
Clinical Trial

Four phase 1 trials to evaluate the safety and pharmacokinetic profile of single and repeated dosing of SCO-101 in adult male and female volunteers

Troels K Bergmann et al. Basic Clin Pharmacol Toxicol. 2020 Oct.

Abstract

SCO-101 (Endovion) was discontinued 20 years ago as a new drug under development against sickle cell anaemia. Data from the phase 1 studies remained unpublished. New data indicate that SCO-101 might be efficacious as add-on therapy in cancer. Thus, we report the results from the four phase 1 trials performed between 2001 and 2002. Adult volunteers received SCO-101 or placebo in four independent trials. Adverse events were recorded, and SCO-101 was determined for pharmacokinetic analysis. Ninety-two volunteers completed the trials. The most remarkable adverse effect was a transient and dose-dependent increase in unconjugated bilirubin. Plasma SCO-101 elimination was approximately log linear, with apparent oral clearances of between 315 and 2103 mL/h for single doses, and between 121 and 2433 mL/h at steady state following oral administration. There was a marked decrease in clearance with increasing dose, and for repeated dose versus single dose. Tmax was greater, and Cmax and AUC∞ were lower in the fed state compared to the fasted state. Exposure was equivalent in males and females and for African Americans and Caucasians. In conclusion, SCO-101 appears to be a safe drug with a predictable PK profile. Its efficacy as add-on to standard anticancer drugs has yet to be defined.

Keywords: cancer chemotherapy; development; discovery and development; drug; drug discovery; drug discovery and development; pharmacokinetics; safety evaluation; safety pharmacology.

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Conflict of interest statement

TK Bergmann has not received any honoraria for the work. However, Scandion Oncology A/S has compensated The University of Southern Denmark for the time spent on the project. TB Stage has done consulting for Pfizer and has received personal fees for teaching for Pfizer, Eisai and Novartis. TB Stage has not received any honoraria for the work. However, Scandion Oncology A/S has compensated The University of Southern Denmark for the time spent on the project. J Stenvang and N Brünner are employees, founders and stock owners in Scandion Oncology A/S. PM Vestlev and NL Roest are employees and stock owners in Scandion Oncology A/S. P Christophersen is employee, founder and stock owner in Saniona A/S, which possess a minority share part in Scandion Oncology. TA Jacobsen is an employee and stock owner in Saniona A/S, which possess a minority share part in Scandion Oncology A/S.

Figures

FIGURE 1
FIGURE 1
Structural formula of SCO‐101. Molecular weight is 495.19 g/mol
FIGURE 2
FIGURE 2
Overview of trial pharmacokinetic sampling. Arrow—SCO‐101 oral dose. Black bar—PK sampling
FIGURE 3
FIGURE 3
Unconjugated bilirubin levels for single and repeated doses of SCO‐101. The lines represent means (±SD). Follow‐up was carried out at approximately day 24
FIGURE 4
FIGURE 4
A, Plasma concentrations of SCO‐101 for the dose escalating experiment (Trial 1). Lines represent cohort means. The two 100 mg cohorts represent the predominantly African American cohort (AA) and the Caucasian cohort (CAU), respectively. B, Plasma concentration of SCO‐101 for the 10 mg cohort (Trial 2). Lines represent cohort means. C, Plasma concentration of SCO‐101 for the 50 mg cohort (Trial 2). Lines represent cohort means. D, Plasma concentration of SCO‐101 for the 150 mg cohort (Trial 2). Lines represent cohort means. E, Plasma concentration of SCO‐101 for the fasted and fed cohorts (100 mg single dose) (Trial 4). The line represents the cohort mean. F, Plasma concentration of SCO‐101 for the 100 mg female cohort (Trial 4). The line represents the cohort mean [Correction Statement: Correction added on 24 August 2020 after first online publication: Figures 4A and 4E were previously swapped and have been corrected in this version.]
FIGURE 5
FIGURE 5
Area under the curve for single doses of SCO‐101
FIGURE 6
FIGURE 6
Box plots of C max and area under the curve for Trial 1 of African Americans and Caucasians. The upper range for AUCInf for African Americans was 317 732 ng/mL*h (not shown in the figure)
See this image and copyright information in PMC

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