NCT02706535

A Cross-over Study to Evaluate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics (PK) of GSK525762 in Healthy Female Subjects of Non Child Bearing Potential

Completed Phase 1 Last updated 16 November 2020

What this trial tests

Phase 1 trial testing GSK525762 Besylate Tablets in Drug Interactions in 29 participants. Completed in 6 January 2017.

Timeline

5 May 2016

Primary endpoint
6 January 2017

6 January 2017

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	29
Start date	5 May 2016
Primary completion	6 January 2017
Estimated completion	6 January 2017
Sites	1 location across United States

Drugs / interventions tested

• GSK525762 Besylate Tablets — full drug profile →
• Itraconazole 200 mg — full drug profile →
• Rifampicin 300 mg

Conditions studied

• Drug Interactions — all drugs for Drug Interactions →
• Neoplasms — all drugs for Neoplasms →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 70, female only, with Drug Interactions or Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This is a Phase I, single center, two-part, randomized, open label, cross-over study. Part 1 of this study will evaluate the PK, safety, and tolerability of GSK525762 when administered alone and when co-administered following repeat dosing of itraconazole, a known strong inhibitor of Cytochrome P450 3A4 (CYP3A4) and a Para-glycoprotein (Pgp) inhibitor. Part 1 will consist of 2 Cohorts with preliminary PK and safety data obtained from Cohort 1 informing Cohort 2. Part 2 (one Cohort) of the study will evaluate the PK, safety, and tolerability of GSK525762 when administered alone and when co-administered following repeat dosing of rifampicin, a known potent inducer of CYP3A4. In vitro inhibition data indicate CYP3A4 may be the major route of clearance for GSK525762 and co-administration of drug therapies which modulate CYP3A4 (i.e.CYP3A4 inhibitors and inducers) is likely to alter the exposure of GSK525762 (i.e. increase or decrease exposure, respectively). The data generated from this current study to justify exclusion criteria on concomitant medications which affect CYP3A4 or Pgp and also inform potential dose modification in case of co-administration with medication affecting CYP3A4 activity. All subjects will undergo a screening visit within 28 days of the first dose of study drug followed by one treatment period and a follow-up visit 7-10 days after the last dose of GSK525762. Subjects in Part 1 will participate in the study for up to 45 days and subjects in Part 2 will participate for up to 56 days.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Drug Discovery Targeting Bromodomain-Containing Protein 4.
   Liu Z, Wang P, Chen H, Wold EA, et al · · 2017 · cited 234× · PMID 28195723 · DOI 10.1021/acs.jmedchem.6b01761
2. Bromodomain inhibitors and cancer therapy: From structures to applications.
   Pérez-Salvia M, Esteller M. · · 2017 · cited 197× · PMID 27911230 · DOI 10.1080/15592294.2016.1265710
3. Epigenetics-targeted drugs: current paradigms and future challenges.
   Dai W, Qiao X, Fang Y, Guo R, et al · · 2024 · cited 131× · PMID 39592582 · DOI 10.1038/s41392-024-02039-0
4. Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.
   Wang ZQ, Zhang ZC, Wu YY, Pi YN, et al · · 2023 · cited 128× · PMID 37926722 · DOI 10.1038/s41392-023-01647-6
5. Targeting Bromodomain and Extraterminal Proteins for Drug Discovery: From Current Progress to Technological Development.
   Tang P, Zhang J, Liu J, Chiang CM, et al · · 2021 · cited 109× · PMID 33616410 · DOI 10.1021/acs.jmedchem.0c01487
6. BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.
   To KKW, Xing E, Larue RC, Li PK. · · 2023 · cited 64× · PMID 37049806 · DOI 10.3390/molecules28073043
7. BRD4: An emerging prospective therapeutic target in glioma.
   Yang H, Wei L, Xun Y, Yang A, et al · · 2021 · cited 40× · PMID 33851008 · DOI 10.1016/j.omto.2021.03.005
8. Targeting lysine acetylation readers and writers.
   Zhou MM, Cole PA. · · 2025 · cited 28× · PMID 39572658 · DOI 10.1038/s41573-024-01080-6