Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents to Treat Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
- Conditions
- Neoplasms
- Interventions
- Drug: GSK3326595Drug: 5-Azacitidine
- Registration Number
- NCT03614728
- Lead Sponsor
- GlaxoSmithKline
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 30
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 Dose expansion: Participants receiving GSK3326595+5-Azacitidine 5-Azacitidine - Part 2 Dose expansion: Participants receiving GSK3326595+5-Azacitidine GSK3326595 - Part 2 Dose escalation : Participants receiving GSK3326595+5-Azacitidine 5-Azacitidine - Part 1: Participants receiving GSK3326595 GSK3326595 - Part 2 Dose escalation : Participants receiving GSK3326595+5-Azacitidine GSK3326595 -
- Primary Outcome Measures
Name Time Method Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) 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) 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 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) 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 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 Outcome Measures
Name Time Method Part 1: Number of Participants With Common Non-STEAEs and STEAEs Up to 30.8 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. An 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. 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. TEAEs which were not serious, were considered as non-STEAEs.
Part 1: Number of Participants With AEs by Severity Up to 30.8 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. Severity of each AE was reported during the study and was assigned a grade according to the NCI-CTCAE. AEs severity were graded as: Grade 1=mild; Grade 2=moderate; Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening consequences and Grade 5=death related to AE.
Part 1: Number of Participants With DLTs 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 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.
Part 1: Overall Response Rate Up to 30.8 months Overall response rate is defined as the percentage of participants achieving a CR, mCR, or PR, per IWG criteria, where CR=Bone marrow: \<=5% 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. Percentage values are rounded off.
Part 1: Progression Free Survival Up to 30.8 months Progression free survival is defined as time from first dose to disease progression, as defined by IWG criteria, or death due to any cause, whichever occurs earlier. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Part 1: Overall Survival Up to 30.8 months Overall survival is defined as time from first dose to death due to any cause.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595. Time invariance was calculated as the ratio of AUC(0-24) on Day 15 divided by AUC(0-infinity) on Day 1 for GSK3326595.
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 Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595. Accumulation ratio was calculated as the ratio of AUC(0-24) on Day 15 divided by AUC(0-24) on Day 1 for GSK3326595.
Part 2: Complete Remission (CR) Rate Up to 3 years and 2 months Complete remission rate is defined as percentage of participants achieving a CR per IWG criteria.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
Part 2: Overall Response Rate Up to 3 years and 2 months Overall response rate is defined as the percentage of participants achieving a CR, mCR, or PR, per IWG criteria.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.
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 Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.
Trial Locations
- Locations (1)
GSK Investigational Site
🇨🇦Toronto, Ontario, Canada