Clinical Trials/NCT03614728

NCT03614728

Terminated

Phase 1

A Phase I/II Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents in Participants With Myelodysplastic Syndrome and Acute Myeloid Leukaemia

GlaxoSmithKline1 site in 1 country30 target enrollmentOctober 16, 2018

ConditionsNeoplasms

InterventionsGSK3326595 5-Azacitidine

DrugsGSK3326595 5-Azacitidine

Overview

Phase: Phase 1
Intervention: GSK3326595
Conditions: Neoplasms
Sponsor: GlaxoSmithKline
Enrollment: 30
Locations: 1
Primary Endpoint: Part 1: Percentage of Participants With Clinical Benefit Rate (CBR)
Status: Terminated
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study will evaluate the safety, tolerability, and clinical activity of GSK3326595 in participants with relapsed and refractory MDS, chronic myelomonocytic leukemia (CMML), and AML. The study will be conducted in 2 parts: Part 1 will determine the clinical benefit rate (CBR) of GSK3326595 in monotherapy and Part 2 will be expanded to study GSK3326595 in combination with 5-Azacitidine which will be composed of a dose escalation phase followed by dose expansion cohort of GSK3326595.

Registry

clinicaltrials.gov

Start Date

October 16, 2018

End Date

January 11, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Males and females greater than or equal to (\>=)18 years of age (at the time consent is obtained).
•Diagnosis of MDS, CMML or AML
•Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 or 2
•Adequate organ function
•A woman of childbearing potential (WOCBP) must have a negative highly sensitive serum pregnancy test within 7 days before the first dose of study intervention.

Exclusion Criteria

•History of, or known, central nervous system (CNS) involvement
•Prior solid organ transplantation
•Known allergies, hypersensitivity, or intolerance to GSK3326595 or 5-Azacitidine or its excipient
•Prior therapy with any Protein arginine methyl transferase 5 (PRMT5) inhibitor
•History of a second malignancy, excluding non-melanoma skin cell cancer, within the last three years
•Active severe or uncontrolled infection
•History of optic nerve neuropathy or neuritis.
•History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

Arms & Interventions

Part 1: Participants receiving GSK3326595

Intervention: GSK3326595

Part 2 Dose escalation : Participants receiving GSK3326595+5-Azacitidine

Intervention: GSK3326595

Part 2 Dose escalation : Participants receiving GSK3326595+5-Azacitidine

Intervention: 5-Azacitidine

Part 2 Dose expansion: Participants receiving GSK3326595+5-Azacitidine

Intervention: GSK3326595

Part 2 Dose expansion: Participants receiving GSK3326595+5-Azacitidine

Intervention: 5-Azacitidine

Outcomes

Primary Outcomes

Part 1: Percentage of Participants With Clinical Benefit Rate (CBR)

Time Frame: Up to 30.8 months

CBR is defined as the percentage of participants achieving a complete remission (CR), complete marrow remission (mCR), partial remission (PR), stable disease (SD) lasting at least 8 weeks, or hematologic improvement (HI), per International Working Group (IWG) criteria, where CR=Bone marrow:\<=5 percent(%) myeloblasts with normal maturation of all cell lines; PR=Bone marrow blasts decreased by \>=50% over pre-treatment but still \>5%; mCR=Bone marrow: \<=5% myeloblasts and decrease by \>=50% over pre-treatment; SD= Failure to achieve at least PR, but no evidence of progression \>8 weeks; HI=Erythroid (E): hemoglobin increase of \>1.5 grams per deciliter (g/dL), HI-Platelet: increase of \>30,000/milliliter (mL) (starting with \>20,000/mL) and increase from \<20,000/mL to \>20,000/mL by \>100%; HI-Neutrophil: increase of \>100% and \>500/microliter. Percentage values are rounded off.

Part 2: Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment Emergent Adverse Events (STEAEs)

Time Frame: Up to 3 years and 2 months

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. Treatment emergent adverse event (TEAE) is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with non-STEAEs and STEAEs were planned to be assessed.

Part 2: Number of Participants With AEs by Severity

Time Frame: Up to 3 years and 2 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with AEs by severity were planned to be assessed.

Part 2: Number of Participants With Dose Limiting Toxicities (DLTs)

Time Frame: Up to 28 days

An event is considered to be a DLT if the event occurs within the first 28 days of treatment meeting one of the following criteria of toxicity, Hematologic: Grade 4 or greater treatment-emergent neutropenia, anemia, or thrombocytopenia, lasting for \>=14 days in the absence of Investigational Product, that cannot be attributed to underlying disease as described in National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4; Non-hematologic: Hepatic toxicity that meets Liver Stopping Criteria, Grade 3 nausea, vomiting or diarrhea that does not improve within 72 hours despite appropriate supportive treatments, Grade 4 or greater nausea, vomiting, or diarrhea of any duration, Any other Grade 3 or greater clinically significant non-hematologic toxicity; Other: Inability to receive all planned doses, dose interruption and Grade 2 or higher toxicity. Number of participants with DLTs were planned to be assessed.

Part 2: Number of Participants With AEs Leading to Dose Interruptions, Dose Reductions and Treatment Discontinuation Due to AEs

Time Frame: Up to 3 years and 2 months

Number of participants with AEs leading to dose interruptions, dose reductions and treatment discontinuation due to AEs were planned to be assessed.

Secondary Outcomes

Part 1: Number of Participants With Common Non-STEAEs and STEAEs(Up to 30.8 months)
Part 1: Number of Participants With AEs by Severity(Up to 30.8 months)
Part 1: Number of Participants With DLTs(Up to 28 days)
Part 1: Overall Response Rate(Up to 30.8 months)
Part 1: Progression Free Survival(Up to 30.8 months)
Part 1: Overall Survival(Up to 30.8 months)
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: Cmax of GSK3326595 Following Administration of Repeat Dose(Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: Time of Maximum Concentration Observed (Tmax) of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: Tmax of GSK3326595 Following Administration of Repeat Dose(Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: t1/2 of GSK3326595 Following Administration of Repeat Dose(Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: Area Under Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within Participant Across All Treatments (AUC[0-t]) of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: AUC(0-t) of GSK3326595 Following Administration of Repeat Dose(Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: AUC From 0 Hours to the Time of Next Dosing (AUC[0-tau]) of GSK3326595(Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: AUC(0-inf) of GSK3326595 Following Administration of Repeat Dose(Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: Oral Clearance (CL/F) of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: CL/F of GSK3326595 Following Administration of Repeat Dose(Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 1: Time Invariance Following Administration of GSK3326595(Days1and15:Pre-dose(within 1hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hour(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour),24hours(+/-2hour)post-dose)
Part 1: Accumulation Ratio Following Administration of GSK3326595(Days1and15:Pre-dose(within 1hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hour(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour),24hours(+/-2hour)post-dose)
Part 2: Complete Remission (CR) Rate(Up to 3 years and 2 months)
Part 2: Cmax of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: Cmax of GSK3326595 Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: Cmax of 5-Azacitidine Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: AUC(0-tau) Following Administration of 5-Azacitidine(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: CL/F of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: CL/F of GSK3326595 Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: CL/F of 5-Azacitidine Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: CL/F of 5-Azacitidine Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: Time Invariance Following Administration of GSK3326595(Days 1 and 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour)post-dose)
Part 2: Time Invariance Following Administration of 5-Azacitidine(Days 1 and 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: Accumulation Ratio Following Administration of GSK3326595(Day 1 and 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: Accumulation Ratio Following Administration of 5-Azacitidine(Days 1 and 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: Overall Response Rate(Up to 3 years and 2 months)
Part 2: Cmax of 5-Azacitidine Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: t1/2 of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: t1/2 of GSK3326595 Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: t1/2 of 5-Azacitidine Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: t1/2 of 5-Azacitidine Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: AUC(0-t) of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: AUC(0-t) of GSK3326595 Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: Tmax of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: Tmax of GSK3326595 Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: Tmax of 5-Azacitidine Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: Tmax of 5-Azacitidine Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: AUC(0-t) of 5-Azacitidine Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: AUC(0-t) of 5-Azacitidine Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: AUC(0-inf) of GSK3326595 Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: AUC(0-inf) of GSK3326595 Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)
Part 2: AUC(0-inf) of 5-Azacitidine Following Administration of Single Dose(Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: AUC(0-inf) of 5-Azacitidine Following Administration of Repeat Dose(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose)
Part 2: AUC(0-tau) Following Administration of GSK3326595(Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose)