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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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. / Bergmann, Troels K.; Stage, Tore B.; Stenvang, Jan; Christophersen, Palle; Jacobsen, Thomas A.; Roest, Nicklas L.; Vestlev, Peter M.; Brunner, Nils.

In: Basic & Clinical Pharmacology & Toxicology, Vol. 127, No. 4, 2020, p. 329-337.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bergmann, TK, Stage, TB, Stenvang, J, Christophersen, P, Jacobsen, TA, Roest, NL, Vestlev, PM & Brunner, N 2020, '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', Basic & Clinical Pharmacology & Toxicology, vol. 127, no. 4, pp. 329-337. https://doi.org/10.1111/bcpt.13466

APA

Bergmann, T. K., Stage, T. B., Stenvang, J., Christophersen, P., Jacobsen, T. A., Roest, N. L., Vestlev, P. M., & Brunner, N. (2020). 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. Basic & Clinical Pharmacology & Toxicology, 127(4), 329-337. https://doi.org/10.1111/bcpt.13466

Vancouver

Bergmann TK, Stage TB, Stenvang J, Christophersen P, Jacobsen TA, Roest NL et al. 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. Basic & Clinical Pharmacology & Toxicology. 2020;127(4):329-337. https://doi.org/10.1111/bcpt.13466

Author

Bergmann, Troels K. ; Stage, Tore B. ; Stenvang, Jan ; Christophersen, Palle ; Jacobsen, Thomas A. ; Roest, Nicklas L. ; Vestlev, Peter M. ; Brunner, Nils. / 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. In: Basic & Clinical Pharmacology & Toxicology. 2020 ; Vol. 127, No. 4. pp. 329-337.

Bibtex

@article{e206d00c8caf49b6af120b981d1cf13d,
title = "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",
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.T(max)was greater, andC(max)and AUC(infinity)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, RESISTANCE, CANCER, CELLS",
author = "Bergmann, {Troels K.} and Stage, {Tore B.} and Jan Stenvang and Palle Christophersen and Jacobsen, {Thomas A.} and Roest, {Nicklas L.} and Vestlev, {Peter M.} and Nils Brunner",
year = "2020",
doi = "10.1111/bcpt.13466",
language = "English",
volume = "127",
pages = "329--337",
journal = "Basic and Clinical Pharmacology and Toxicology",
issn = "1742-7835",
publisher = "Wiley-Blackwell",
number = "4",

}

RIS

TY - JOUR

T1 - 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

AU - Bergmann, Troels K.

AU - Stage, Tore B.

AU - Stenvang, Jan

AU - Christophersen, Palle

AU - Jacobsen, Thomas A.

AU - Roest, Nicklas L.

AU - Vestlev, Peter M.

AU - Brunner, Nils

PY - 2020

Y1 - 2020

N2 - 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.T(max)was greater, andC(max)and AUC(infinity)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.

AB - 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.T(max)was greater, andC(max)and AUC(infinity)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.

KW - cancer chemotherapy

KW - development

KW - discovery and development

KW - drug

KW - drug discovery

KW - drug discovery and development

KW - pharmacokinetics

KW - safety evaluation

KW - safety pharmacology

KW - RESISTANCE

KW - CANCER

KW - CELLS

U2 - 10.1111/bcpt.13466

DO - 10.1111/bcpt.13466

M3 - Journal article

C2 - 32628359

VL - 127

SP - 329

EP - 337

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 4

ER -

ID: 248332947