The Effect of Glucose Level and Diabetes Mellitus on Ctrough of Olaparib

Ovary Cancer Clinical Trial

Official title:

The Effect of Glucose Level and Diabetes Mellitus on the Plasma Minimum Steady-state Concentration Ctrough of Olaparib in Patients With Ovarian Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05081765
• Other study ID #: 697/20
• Status: Recruiting
• Start date: September 20, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: October 2021
• Source: Poznan University of Medical Sciences
• Contact: Joanna i Stanislawiak-Rudowicz, MD, PhD
• Phone: 0048605781967
• Email: stanisl[@]interia.pl
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Monitored therapy of olaparib concentrations in the blood of diabetic population probably will assess the need for individual dosing of the drug.

The project concerns on the monitored therapy of olaparib in a population of patients with DM, hyperglycemia and normal glucose level.

Currently, there are no studies assessing the effect of comorbidities and of the administered drugs on the pharmacokinetics of olaparib.

Description:

The research is conducted at the Poznan University of Medical Sciences, and the Poznan, Poland with the approval from the Bioethics Committee, University of Medical Sciences, Poznan, Poland (697/20). The subjects of the research: the C through of olaparib in the patients with ovarian cancer who received olaparib The patients included in the study if they met the following criteria: treatment with olaparib above four days, age >18 years; no history of allergy to olaparib. The chief criteria for exclusion included allergy to olaparib, age under 18 years, status of the patient which do not allowed the patient to continue the study.

Administration and blood sampling The patients with an ovarian cancer treated with olaparib (tablets in dose 300mg/12h, 250mg/12h, 200 mg/12h or capsules 400mg/12h, 200mg/12h, 100 mg/12h).

Blood samples (2 mL) collected at steady state before morning drug administration. The blood samples transferred into heparinised tubes and centrifuged at 2880 g for 10 min at 4 °C. Next the plasma transferred to propylene tubes and stored at - 20 °C until analysis.

Assays The concentrations of olaparib in plasma assayed using the high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. The method validated according to European Medicines Agency guideline. The method validation confirmed good precision (CV% <15%), accuracy (92.3-115.0%) and linearity (r=0.9994) in the range of 100-4000 ng/mL.

The severity of olaparib adverse effects assessed by CTCAE (Common Terminology Criteria for Adverse Events) v.5.0 scale.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2022
• Est. primary completion date: October 15, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ovarian cancer patients treated with olaparib above than 4 days

• patient who gave permission to take part in the trial

• age >18 years

• no history of allergy to olaparib

Exclusion Criteria:

• allergy to olaparib,

• age under 18 years,

• status of the patient which do not allowed the patient to continue the study.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Ovarian Neoplasms
• Ovary Cancer

Intervention

Drug:
• Lynparza® (AstraZeneca Pharma Poland Sp. z o.o.)
correlation between C through and taken drug

Device:
• Lynparza
correlation between C through and taken drug

Locations

Country	Name	City	State
Poland	University od Medical Sciences	Poznan

Sponsors (2)

Lead Sponsor	Collaborator
Poznan University of Medical Sciences	Poznan University Hospital of Lord's Transfiguration

Country where clinical trial is conducted

Poland, 

References & Publications (13)

Debska S, Kubicka J, Czyzykowski R, Habib M, Potemski P. [PARP inhibitors--theoretical basis and clinical application]. Postepy Hig Med Dosw (Online). 2012 May 30;66:311-21. Review. Polish. — View Citation

Dostalek M, Akhlaghi F, Puzanovova M. Effect of diabetes mellitus on pharmacokinetic and pharmacodynamic properties of drugs. Clin Pharmacokinet. 2012 Aug 1;51(8):481-99. doi: 10.2165/11631900-000000000-00000. Review. — View Citation

Dostalek M, Court MH, Yan B, Akhlaghi F. Significantly reduced cytochrome P450 3A4 expression and activity in liver from humans with diabetes mellitus. Br J Pharmacol. 2011 Jul;163(5):937-47. doi: 10.1111/j.1476-5381.2011.01270.x. — View Citation

Friedlander M, Banerjee S, Mileshkin L, Scott C, Shannon C, Goh J. Practical guidance on the use of olaparib capsules as maintenance therapy for women with BRCA mutations and platinum-sensitive recurrent ovarian cancer. Asia Pac J Clin Oncol. 2016 Dec;12(4):323-331. doi: 10.1111/ajco.12636. Review. Erratum in: Asia Pac J Clin Oncol. 2017 Aug;13(4):337. — View Citation

Karbownik A, Stachowiak A, Urjasz H, Sobanska K, Szczecinska A, Grabowski T, Stanislawiak-Rudowicz J, Wolc A, Grzeskowiak E, Szalek E. The oxidation and hypoglycaemic effect of sorafenib in streptozotocin-induced diabetic rats. Pharmacol Rep. 2020 Feb;72(1):254-259. doi: 10.1007/s43440-019-00021-0. Epub 2020 Jan 8. Erratum in: Pharmacol Rep. 2021 Oct;73(5):1483. — View Citation

Karbownik A, Szalek E, Sobanska K, Grabowski T, Wolc A, Grzeskowiak E. The alteration of pharmacokinetics of erlotinib and OSI420 in type 1 diabetic rabbits. Pharmacol Rep. 2016 Oct;68(5):964-8. doi: 10.1016/j.pharep.2016.04.015. Epub 2016 May 6. — View Citation

Karbownik A, Szalek E, Sobanska K, Klupczynska A, Plewa S, Grabowski T, Wolc A, Moch M, Kokot ZJ, Grzeskowiak E. A pharmacokinetic study on lapatinib in type 2 diabetic rats. Pharmacol Rep. 2018 Apr;70(2):191-195. doi: 10.1016/j.pharep.2017.09.003. Epub 2017 Sep 18. — View Citation

Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott CL, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Dougherty B, Orr M, Hodgson D, Barrett JC, Matulonis U. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014 Jul;15(8):852-61. doi: 10.1016/S1470-2045(14)70228-1. Epub 2014 May 31. Erratum in: Lancet Oncol. 2015 Apr;16(4):e158. — View Citation

Porazka J, Szalek E, Polom W, Czajkowski M, Grabowski T, Matuszewski M, Grzeskowiak E. Influence of Obesity and Type 2 Diabetes Mellitus on the Pharmacokinetics of Tramadol After Single Oral Dose Administration. Eur J Drug Metab Pharmacokinet. 2019 Aug;44(4):579-584. doi: 10.1007/s13318-019-00543-1. — View Citation

Stachowiak A, Szalek E, Karbownik A, Lojko A, Porazka J, Przewozna I, Grabowski T, Wolc A, Grzeskowiak E. The Influence of Diabetes Mellitus on Glucuronidation and Sulphation of Paracetamol in Patients with Febrile Neutropenia. Eur J Drug Metab Pharmacokinet. 2019 Apr;44(2):289-294. doi: 10.1007/s13318-018-0508-4. — View Citation

Szalek E, Karbownik A, Sobanska K, Grabowski T, Polom W, Lewandowska M, Wolc A, Matuszewski M, Grzeskowiak E. The pharmacokinetics and hypoglycaemic effect of sunitinib in the diabetic rabbits. Pharmacol Rep. 2014 Oct;66(5):892-6. doi: 10.1016/j.pharep.2014.05.011. Epub 2014 Jun 6. — View Citation

Tran M, Elbarbry F. Influence of diabetes mellitus on pharmacokinetics of drugs. MOJ Bioequiv Availab. 2016;2(1):3-4.

Wisnik E, Ryksa M, Koter-Michalak M. [PARP1 inhibitors: contemporary attempts at their use in anticancer therapy and future perspective]. Postepy Hig Med Dosw (Online). 2016 Apr 13;70:280-94. Review. Polish. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	correlation between glucose level and C through.olaparib in the blood of the patients with ovarian cancer	There is idea to check the correlation of C through of the olaparib taken by the patients with diabetes melitus and ovarian cancer and the correlation of C through and glucose of the patients with hyperglycemia diagnosed during olaparib treatment	through study completion, an average of 1 year

External Links

•   Onkol Prakt Klin Edu 2018;4(3):167-178.
•   Summary of product characteristic