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A Phase I Dose Escalation Study of GSK2879552 in Subjects With Acute Myeloid Leukemia (AML)

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Terminated
CT.gov ID
NCT02177812
Collaborator
(none)
41
Enrollment
8
Locations
2
Arms
39.4
Actual Duration (Months)
5.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a phase I, open-label study to determine recommended phase 2 dose (RP2D) and regimen for the orally administered lysine specific demethylase 1 (LSD1) inhibitor GSK2879552, alone or in combination with All-Trans Retinoic Acid (ATRA). The recommended dose and regimen will be selected based on the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles observed after the treatment of subjects with relapsed/refractory AML. The study consists of two parts. Part 1 will identify the maximum tolerated dose (MTD) and/or RP2D using a dose-escalation procedure. Dose escalations will be guided by the Neuenschwander-continual reassessment method (N-CRM). PK/PD expansion cohorts will also be included in Part 1 to characterize the range of biologically effective doses by assessing PD markers and obtain additional PK data. Part 2 will explore further the safety, tolerability, and clinical activity of GSK2879552, alone or in combination with ATRA, at the RP2D in subjects with AML.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
41 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2879552 Given Orally in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
Actual Study Start Date :
Aug 27, 2014
Actual Primary Completion Date :
Dec 8, 2017
Actual Study Completion Date :
Dec 8, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation Phase (Part 1)

The safety and PK/PD data will be reviewed prior to the dose decision, and the dose escalation will be guided by the Neuenschwander -continuous reassessment method (N-CRM).The dose escalation will complete when RP2D is determined. The RP2D will be the MTD or a lower dose that provides adequate PK exposure and biologic activity with superior tolerability.

Drug: GSK2879552
GSK2879552 capsules contain 0.25 mg, 0.5 mg, 2 mg or 5 mg of GSK2879552 as parent. The initial dosing regimen will be continuous oral daily dosing.

Drug: ATRA
ATRA (Tretinoin) will be supplied as a 10 mg capsule for oral administration. The initial dosing regimen will be continuous oral twice daily dosing
Experimental: Expansion Phase (Part 2)

Once the MTD and/or RP2D has been determined in Part 1, an expansion cohort of up to 30 subjects will be enrolled in order to characterize the clinical activity and safety profile of the RP2D. Subjects may continue treatment in the study until disease progression, unacceptable toxicity, or withdrawal of consent.

Drug: GSK2879552
GSK2879552 capsules contain 0.25 mg, 0.5 mg, 2 mg or 5 mg of GSK2879552 as parent. The initial dosing regimen will be continuous oral daily dosing.

Drug: ATRA
ATRA (Tretinoin) will be supplied as a 10 mg capsule for oral administration. The initial dosing regimen will be continuous oral twice daily dosing

Outcome Measures

Primary Outcome Measures

  1. Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Median of 4 weeks of drug exposure]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function.

  2. Part 1: Number of Participants With Dose Limiting Toxicities (DLT) [Median of 4 weeks of drug exposure]

    An event was considered a DLT if it occursed within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event was unrelated to treatment: hematologic DLT included myelosuppression, Grade >=3 non-hematologic toxicity that is considered clinically significant and lasts >72 hours, Grade 2 toxicity that in the judgment of the investigator and GSK Medical Monitor is dose-limiting and treatment delay of >=42 days due to unresolved toxicity.

  3. Part 1: Number of Participants With AE Leading to Dose Reductions or Delays [Median of 4 weeks of drug exposure]

    The number of participants who had any dose reduction or delay have been presented.

  4. Part 1: Number of Participants With Withdrawals Due to Toxicities [Median of 4 weeks of drug exposure]

    Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.

  5. Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range [Median of 4 weeks of drug exposure]

    Blood samples were collected to assess clinical chemistry parameters like urea/blood urea nitrogen (BUN), calcium, potassium, aspartate aminotransferase (AST), total bilirubin, direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, glucose, total carbon dioxide (CO2), gamma glutamyl transferase (GGT), albumin, sodium, alkaline phosphatase, total protein, phosphate, lactate dehydrogenase (LDH). Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst case post Baseline is reported.

  6. Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline [Median of 4 weeks of drug exposure]

    Blood samples were collected for analysis of clinical chemistry parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any increase in grade of worst-case on-therapy has been provided.

  7. Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range [Median of 4 weeks of drug exposure]

    Blood samples were collected to assess hematology parameters like mean corpuscle hemoglobin concentration (MCHC), mean corpuscle hemoglobin (MCH), mean corpuscle volume (MCV) mean platelet volume (MPV), basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, platelet count, Red blood cell (RBC) count, reticulocytes, White Blood Cell (WBC) count. Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst post Baseline were reported. NA indicates that data were not available as standard deviation could not be calculated for a single participant.

  8. Number of Participants With Hematology Toxicity Grade Changes From Baseline [Median of 4 weeks of drug exposure]

    Blood samples were collected for analysis of hematology parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any grade increase worst-case on-therapy has been provided.

  9. Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Median of 4 weeks of drug exposure]

    SBP and DBP were measured after resting for 5 minutes in semi-supine position. Vital signs were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. An increase is defined as an increase in CTCAE grade relative to Baseline grade. For SBP Grade 0 (<120 millimeters of mercury [mmHg]), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (>=160 mmHg). For DBP Grade 0 (<80 mmHg), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (>=100 mmHg). Data for worst-case post Baseline is reported.

  10. Part 1: Number of Participants With Change From Baseline in Heart Rate [Median of 4 weeks of drug exposure]

    Heart rate was measured after restings for 5 minutes in semi-supine position. Data for participants with heart rate decreased to < 60 beats per minute (bpm), normal or no change, increase to > 100 bpm. Data for worst post Baseline were reported.

  11. Part 1: Number of Participants With Change From Baseline in Temperature [Median of 4 weeks of drug exposure]

    Temperature was measured after resting for 5 minutes in semi-supine position. Data for participants with temperature decreased to <=35 Celsius, normal or no change, increase to >=38 Celsius at worst-case post Baseline is reported.

  12. Part 1: Number of Participants With Change From Baseline in Respiratory Rate [Median of 4 weeks of drug exposure]

    Respiration rate was measured after resting for 5 minutes in semi-supine position. Data for worst case post-Baseline has been reported. Number of participants with respiratory rate decrease to <12 and increase to >25 has been reported.

  13. Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings [Median of 4 weeks of drug exposure]

    A single 12-lead ECG was performed in semi-recumbent or supine position after 5 minutes of rest for the participant. An ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals was used. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported.

  14. Part 1: Number of Participants With Abnormal Physical Examinations [Median of 4 weeks of drug exposure]

    Data for participants with abnormal physical examinations parameters was planned to be recorded.

  15. Part 2: Objective Response Rate of Participants [Up to 14 months]

    Objective response rate defined as the percentage of participants who achievied complete remission (CR), partial remission (PR), CRp (as per CR but platelet count <100 x 10^9/L) and morphologic leukemia free state per response criteria. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Secondary Outcome Measures

  1. Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1]

    Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric co-efficient of variation could not be calculated for a single participant.

  2. Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric co-efficient could not be calculated for a single participant.

  3. Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 15]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant.

  4. Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant.

  5. Part 1: Apparent Terminal Phase Half-life (t½) [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant.

  6. Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as standard deviation could not be calculated for a single participant.

  7. Part 1: Accumulation Ratio for GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Accumulation ratio was determined dividing AUC (0-tau) on Day 15 by AUC (0-tau) on Day 1. The ratio of accumulation of GSK2879552 was estimated by calculating the ratio of the geometric least squares (GLS) means of the AUC(0-tau) between Day 15 and Day 1 for all dose levels and the corresponding 90 percent confidence interval (CI) for each ratio.

  8. Part 1:Time Invariance [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. The time invariance of GSK2879552 was estimated by calculating the ratio of the GLS means of the AUC (0-tau) between Day 15 and Day 1 for all dose levels and the corresponding 90 percent CI for each ratio.

  9. Part 1:Percentage of Participants With Objective Response [Median of 4 weeks drug response]

    Objective response rate is defined as the percentage of participants who achieved CR, PR, as per CR but platelet count <100 x 10^9/L and morphologic leukemia free state per response criteria.

  10. Part 1: AUC(0-t), AUC (0-tau) and AUC(0-inf) of ATRA [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1and Day 15]

    Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis.

  11. Part 1: Cmax of ATRA [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

  12. Part 1: Apparent Terminal Phase Half-life (t½) of ATRA [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

  13. Part 1: Time of Occurrence of Cmax (Tmax) of ATRA [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15]

    Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

  14. Part 2: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Up to 14 months]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  15. Part 2: Number of Participants With AE Leading to Dose Reductions or Delays [Up to 14 months]

    The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  16. Part 2: Number of Participants With Withdrawals Due to Toxicities [Up to 14 months]

    Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  17. Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters [Up to 14 months]

    Data was not collected for Part 2 as the study was terminated early during Part 1.

  18. Part 2: Number of Participants With Abnormal Hematology Parameters [Up to 14 months]

    Data was not collected for Part 2 as the study was terminated early during Part 1.

  19. Part 2: Number of Participants With Abnormal Vital Signs [Up to 14 months]

    Data was not collected for Part 2 as the study was terminated early during Part 1.

  20. Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings [Up to 14 months]

    This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  21. Part 2: Number of Participants With Abnormal Physical Examinations [Up to 14 months]

    This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  22. Part 2: Clearance (CL) of GSK2879552 for Part 2 [Day 1 (pre-dose, 0.5 and 3 hours post dose), Days 4, 8 (pre-dose), Day 15 (pre-dose, 0.5, 1, 4, 6 hours), Weeks 4, 5, 6, 7, 8 and every 4 weeks up to Week 48]

    This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  23. Part 2: Volume of Distribution of GSK2879552 for Part 2 [Day 1 (pre-dose, 0.5 and 3 hours post dose), Days 4, 8 (pre-dose), Day 15 (pre-dose, 0.5, 1, 4, 6 hours), Weeks 4, 5, 6, 7, 8 and every 4 weeks up to Week 48]

    This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  24. Number of Participants With Abnormal Covariates: Part 2 [Up to 14 months]

    This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  25. Duration of Response: Part 2 [Up to 14 months]

    This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  26. Time to Time to Response: Part 2 [Up to 14 months]

    This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

  27. Progression-free Survival: Part 2 [Up to 14 months]

    This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Subjects >=18 years of age and provided signed written informed consent.

  • Subjects must have relapsed/refractory AML by world health organization (WHO) classification for which no standard therapies are available or anticipated to result in a durable remission. French- American- British system (FAB) subtype M3 will be excluded.

  • Subjects >= 60 years of age with AML who are not candidates for or have refused standard chemotherapy.

  • Subjects who have previously received an autologous stem cell transplant are allowed if a minimum of 3 months has elapsed from the time of transplant and the subject has recovered from transplant-associated toxicities prior to the first dose of GSK2879552.

  • Subjects with a history of allogeneic stem cell transplant are eligible for study participation provided the following eligibility criteria are met: transplant was >60 days prior to study enrolment; subject has not taken immunosuppressive medications for at least 1 month; no signs or symptoms of graft versus host disease other than Grade 1 skin involvement; no active infection.

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

  • Subjects must be stable and, in the opinion of the investigator, be expected to complete 4 week treatment period.

  • Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.

  • All prior treatment-related toxicities must be National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 <=Grade 1 at the time of enrollment (except for alopecia).

  • Adequate baseline organ function.

  • Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, during the study and for 7 days (GSK2879552 mono therapy) or 30 days (combination with ATRA), following the last dose of study treatment.

  • Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from the administration of the first dose of study treatment until 3 months after the last dose of study treatment to allow for clearance of any altered sperm.

Exclusion Criteria:

  • Active human immunodeficiency virus (HIV), Hepatitis B Virus (HBV) or hepatitis C virus (HCV) infections at the time of screening. Subjects with laboratory evidence of HCV clearance may be enrolled.

  • History of or concurrent malignancy of solid tumours, except: subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled even if less than 5 years have elapsed since treatment. Consult GlaxoSmithKline (GSK) Medical Monitor if unsure whether second malignancies meet requirements specified above.

  • Currently receiving cancer therapy. Hydroxyurea will be allowed.

  • Received major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK2879552 administration.

  • Prior treatment with temozolomide, dacarbazine or procarbazine

  • Prior treatment with poly ADP ribose polymerase (PARP) inhibitors (eg., olaparib, ABT-888)

  • Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower

  • Evidence of severe or uncontrolled systemic diseases. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator

  • Current active liver or biliary disease.

  • Patients at risk of non-AML related major bleeding (e.g. recent gastrointestinal [GI] hemorrhage or neurosurgery).

  • Symptomatic or untreated central nervous system (CNS) leukemia. Subjects are permitted to enroll if previously treated for CNS disease, free of symptoms at the time of screening, and have not required intrathecal chemotherapy at least 1 month prior to study Day 1.

  • Cardiac abnormalities

  • Administration of an investigational drug within 14 days or 5 half-lives, whichever is shorter with a minimum of 14 days preceding the first dose of study treatment(s) in this study.

  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2879552 or LSD1 inhibitors that contraindicates their participation.

  • Lactating female.

  • Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice, pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study treatment(s) until the last dose of study drug.

  • Current use of a prohibited medication including anticoagulants or platelet inhibitors or expected to require any of these medications during treatment with the investigational drug.

  • Previous treatment with GSK2879552 For ATRA Combination arm ONLY

  • Known hypersensitivity to ATRA, parabens (preservatives in the gelatin capsule) or other retinoids.

  • ATRA capsule contains sorbitol. Subjects with rare hereditary problems of fructose intolerance are excluded.

  • History of seizure within 12 months or brain tumor (primary)

  • History of taking mega-dose vitamin A (>25,000 USP U/day) within 3 months from the dosing start.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Augusta Georgia United States 30912
2 GSK Investigational Site Bronx New York United States 10461
3 GSK Investigational Site Bronx New York United States 10467
4 GSK Investigational Site New York New York United States 10065
5 GSK Investigational Site Houston Texas United States 77030
6 GSK Investigational Site Melbourne Victoria Australia 3004
7 GSK Investigational Site Toronto Ontario Canada M5G 2M9
8 GSK Investigational Site Toronto Ontario Canada M5G 2M

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline
  • Study Director: GSK Clinical Trials, GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02177812
Other Study ID Numbers:
  • 200200
First Posted:
Jun 30, 2014
Last Update Posted:
Jun 28, 2019
Last Verified:
Apr 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by GlaxoSmithKline
Oncology
LSD1
GSK2879552
Acute myeloid leukemia
Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute

Study Results

Participant Flow

Recruitment Details A total of 41 participants with relapsed/refractory acute myeloid leukemia (AML) were enrolled in Part 1 at different centers in Australia, Canada and United States. This study was planned to be conducted in 2 parts :Part 1 (dose escalation) and Part 2 (Expansion Cohort).
Pre-assignment Detail This study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study and therefore, Part 2 was not conducted. There were no active participants on study when the study was terminated.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion Part 2: Expansion Cohort
Arm/Group Description Participants received GSK2879552 1 milligram (mg) orally once daily (QD) in fasted condition with approximately 200 milliliter (mL) of water Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with All-Trans Retinoic Acid (ATRA) at a dose of 45 mg per meter square per day (mg/m^2/day). Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in Pharmacokinetic/Pharmacodynamics (PK/PD) Expansion cohort to collect adequate data on safety, PK or PD. In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA
Period Title: Part 1 (Median of 4 Weeks)
STARTED 1 2 7 5 6 4 10 6 0
COMPLETED 1 2 7 4 5 1 1 4 0
NOT COMPLETED 0 0 0 1 1 3 9 2 0
Period Title: Part 1 (Median of 4 Weeks)
STARTED 0 0 0 0 0 0 0 0 0
COMPLETED 0 0 0 0 0 0 0 0 0
NOT COMPLETED 0 0 0 0 0 0 0 0 0

Baseline Characteristics

Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion Part 2: Expansion Cohort Total
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD. In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA. Total of all reporting groups
Overall Participants 1 2 7 5 6 4 10 6 0 41
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
68.0
(NA)
73.5
(2.12)
64.3
(5.77)
61.0
(13.96)
71.7
(4.08)
71.8
(4.03)
63.1
(20.14)
65.5
(19.07)
66.1
(13.47)
Sex: Female, Male (Count of Participants)
Female
0
0%
0
0%
3
42.9%
3
60%
2
33.3%
1
25%
3
30%
1
16.7%
0
NaN
13
31.7%
Male
1
100%
2
100%
4
57.1%
2
40%
4
66.7%
3
75%
7
70%
5
83.3%
0
NaN
28
68.3%
Race/Ethnicity, Customized (Count of Participants)
Black or African American
0
0%
0
0%
0
0%
1
20%
1
16.7%
0
0%
1
10%
0
0%
0
NaN
3
7.3%
Asian - Central/South Asian Heritage
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
NaN
2
4.9%
Asian - East Asian Heritage
0
0%
0
0%
1
14.3%
1
20%
1
16.7%
1
25%
0
0%
0
0%
0
NaN
4
9.8%
Asian - South East Asian Heritage
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
1
10%
0
0%
0
NaN
2
4.9%
White - White/Caucasian/European Heritage
1
100%
2
100%
4
57.1%
3
60%
2
33.3%
2
50%
6
60%
4
66.7%
0
NaN
24
58.5%
Missing
0
0%
0
0%
0
0%
0
0%
2
33.3%
1
25%
2
20%
1
16.7%
0
NaN
6
14.6%

Outcome Measures

1. Primary Outcome
Title Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Description An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population comprised of all participants who received at least one dose of study treatment.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
All AEs
1
100%
2
100%
7
100%
5
100%
6
100%
4
100%
10
100%
6
100%
All SAEs
1
100%
2
100%
7
100%
5
100%
6
100%
3
75%
8
80%
5
83.3%
2. Primary Outcome
Title Part 1: Number of Participants With Dose Limiting Toxicities (DLT)
Description An event was considered a DLT if it occursed within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event was unrelated to treatment: hematologic DLT included myelosuppression, Grade >=3 non-hematologic toxicity that is considered clinically significant and lasts >72 hours, Grade 2 toxicity that in the judgment of the investigator and GSK Medical Monitor is dose-limiting and treatment delay of >=42 days due to unresolved toxicity.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Count of Participants [Participants]
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
0
0%
0
0%
3. Primary Outcome
Title Part 1: Number of Participants With AE Leading to Dose Reductions or Delays
Description The number of participants who had any dose reduction or delay have been presented.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
AEs leading to dose reduction
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
16.7%
AEs leading to dose interruption/delay
0
0%
0
0%
2
28.6%
3
60%
5
83.3%
0
0%
6
60%
1
16.7%
4. Primary Outcome
Title Part 1: Number of Participants With Withdrawals Due to Toxicities
Description Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Count of Participants [Participants]
0
0%
0
0%
0
0%
1
20%
4
66.7%
2
50%
4
40%
2
33.3%
5. Primary Outcome
Title Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range
Description Blood samples were collected to assess clinical chemistry parameters like urea/blood urea nitrogen (BUN), calcium, potassium, aspartate aminotransferase (AST), total bilirubin, direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, glucose, total carbon dioxide (CO2), gamma glutamyl transferase (GGT), albumin, sodium, alkaline phosphatase, total protein, phosphate, lactate dehydrogenase (LDH). Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst case post Baseline is reported.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Direct Bilirubin,to Low,n=1,2,7,5,6,4,10,6
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Direct Bilirubin,to High,n=1,2,7,5,6,4,10,6
0
0%
0
0%
2
28.6%
1
20%
2
33.3%
0
0%
5
50%
3
50%
Chloride,to Low,n=1,2,7,5,6,4,10,6
0
0%
0
0%
0
0%
1
20%
2
33.3%
0
0%
2
20%
1
16.7%
Chloride,to High,n=1,2,7,5,6,4,10,6
0
0%
1
50%
2
28.6%
1
20%
1
16.7%
0
0%
0
0%
0
0%
CO2/Bicarbonate,to Low,n=1,2,7,5,6,4,10,6
0
0%
0
0%
1
14.3%
1
20%
2
33.3%
0
0%
2
20%
2
33.3%
CO2/Bicarbonate,to High,n=1,2,7,5,6,4,10,6
0
0%
0
0%
1
14.3%
2
40%
1
16.7%
0
0%
0
0%
1
16.7%
Lactate Dehydrogenase,to Low,n=1,2,7,5,6,4,10,6
0
0%
0
0%
2
28.6%
2
40%
2
33.3%
0
0%
2
20%
2
33.3%
Lactate Dehydrogenase,to High,n=1,2,7,5,6,4,10,6
1
100%
0
0%
2
28.6%
1
20%
2
33.3%
0
0%
3
30%
2
33.3%
Total Protein,to Low,n=1,2,7,4,6,4,10,6
0
0%
1
50%
3
42.9%
2
40%
4
66.7%
2
50%
3
30%
2
33.3%
Total Protein,to High,n=1,2,7,4,6,4,10,6
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
2
20%
0
0%
Urea/BUN,to Low,n=1,2,7,5,6,4,10,6
1
100%
0
0%
1
14.3%
2
40%
1
16.7%
1
25%
2
20%
0
0%
Urea/BUN,to High,n=1,2,7,5,6,4,10,6
0
0%
0
0%
3
42.9%
1
20%
2
33.3%
0
0%
1
10%
2
33.3%
6. Primary Outcome
Title Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline
Description Blood samples were collected for analysis of clinical chemistry parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any increase in grade of worst-case on-therapy has been provided.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Albumin, n=1,2,7,5,6,4,10,6
1
100%
2
100%
5
71.4%
3
60%
4
66.7%
4
100%
6
60%
3
50%
ALP, n=1,2,7,5,6,4, 10, 6
0
0%
0
0%
3
42.9%
2
40%
1
16.7%
0
0%
3
30%
0
0%
ALT, n=1,2,7,5,6,4,10,6
0
0%
0
0%
4
57.1%
3
60%
1
16.7%
1
25%
5
50%
2
33.3%
AST, n=1,2,7,5,6,4,10,6
1
100%
2
100%
3
42.9%
2
40%
1
16.7%
1
25%
3
30%
1
16.7%
Total bilirubin, n=1,2,7,5,6,4,10,6
1
100%
1
50%
2
28.6%
1
20%
3
50%
0
0%
4
40%
2
33.3%
Hypercalcemia, n=1,2,7,5,6,4,10,6
0
0%
0
0%
0
0%
2
40%
0
0%
0
0%
3
30%
0
0%
Hypoglycemia,n= 1,2,7,5,6,4,10,6
0
0%
0
0%
1
14.3%
2
40%
1
16.7%
0
0%
1
10%
0
0%
Creatinine,n=1,2,7,5,6,4,10,6
0
0%
1
50%
2
28.6%
1
20%
1
16.7%
0
0%
4
40%
1
16.7%
GGT,n=1,2,7,5,3,1,8,3
0
0%
0
0%
5
71.4%
4
80%
2
33.3%
0
0%
5
50%
2
33.3%
Hyperglycemia,n= 0,1,7,5,6,4,9,6
0
0%
0
0%
4
57.1%
2
40%
1
16.7%
0
0%
4
40%
4
66.7%
Hypoglycemia,n=0,1,7,5,6,4,9,6
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
10%
0
0%
Hyperkalemia,n=1,2,7,5,6,4,10,6
0
0%
0
0%
1
14.3%
0
0%
1
16.7%
0
0%
1
10%
0
0%
Hypokalemia,n=1,2,7,5,6,4,10,6
0
0%
0
0%
3
42.9%
4
80%
3
50%
2
50%
6
60%
0
0%
Hypernatremia, n=1,2,7,5,6,4,10,6
0
0%
0
0%
0
0%
1
20%
0
0%
0
0%
1
10%
0
0%
Hyponatremia, n=1,2,7,5,6,4,10,6
1
100%
1
50%
2
28.6%
0
0%
5
83.3%
1
25%
5
50%
3
50%
Phosphorus, n=1,2,7,5,6,4,10,6
1
100%
1
50%
6
85.7%
2
40%
5
83.3%
2
50%
3
30%
2
33.3%
7. Primary Outcome
Title Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range
Description Blood samples were collected to assess hematology parameters like mean corpuscle hemoglobin concentration (MCHC), mean corpuscle hemoglobin (MCH), mean corpuscle volume (MCV) mean platelet volume (MPV), basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, platelet count, Red blood cell (RBC) count, reticulocytes, White Blood Cell (WBC) count. Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst post Baseline were reported. NA indicates that data were not available as standard deviation could not be calculated for a single participant.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Basophils, to Low,n=1,2,7,4,2,2,9,5
0
0%
0
0%
2
28.6%
0
0%
0
0%
0
0%
0
0%
0
0%
Basophils, to High,n=1,2,7,4,2,2,9,5
0
0%
0
0%
1
14.3%
2
40%
1
16.7%
0
0%
0
0%
0
0%
Eosinophils, to Low,n=1,2,7,4,2,2,8,5
0
0%
0
0%
2
28.6%
0
0%
1
16.7%
0
0%
0
0%
0
0%
Eosinophils, to High,n=1,2,7,4,2,2,8,5
0
0%
1
50%
1
14.3%
0
0%
0
0%
0
0%
0
0%
1
16.7%
Hemoglobin, to Low,n=0,0,0,0,2,0,0,1
0
0%
0
0%
Hemoglobin, to High,n=0,0,0,0,2,0,0,1
0
0%
1
50%
Hematocrit, to Low,n=1,2,7,5,6,4,10,6
0
0%
0
0%
0
0%
1
20%
0
0%
0
0%
0
0%
0
0%
Hematocrit, to High,n=1,2,7,5,6,4,10,6
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
MCHC, to Low,n=1,2,7,5,3,2,10,6
1
100%
0
0%
0
0%
0
0%
1
16.7%
0
0%
1
10%
1
16.7%
MCHC, to High,n=1,2,7,5,3,2,10,6
1
100%
0
0%
3
42.9%
2
40%
0
0%
1
25%
2
20%
1
16.7%
MCH, to Low,n=1,2,7,5,3,2,10,6
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
MCH, to High,n=1,2,7,5,3,2,10,6
0
0%
0
0%
0
0%
1
20%
0
0%
0
0%
0
0%
0
0%
MCV, to Low,n=1,2,7,5,6,4,10,6
0
0%
0
0%
2
28.6%
0
0%
1
16.7%
2
50%
0
0%
2
33.3%
MCV, to High,n=1,2,7,5,6,4,10,6
1
100%
0
0%
0
0%
0
0%
0
0%
0
0%
1
10%
0
0%
Monocytes, to Low,n=1,2,7,4,2,2,10,6
0
0%
0
0%
2
28.6%
1
20%
0
0%
1
25%
2
20%
1
16.7%
Monocytes, to High,n=1,2,7,4,2,2,10,6
0
0%
1
50%
4
57.1%
0
0%
1
16.7%
1
25%
2
20%
2
33.3%
MPV, to Low,n=0,0,0,3,6,3,7,6
1
100%
1
50%
1
14.3%
0
0%
1
16.7%
MPV, to High,n=0,0,0,3,6,3,7,6
1
100%
2
100%
0
0%
3
60%
4
66.7%
Nucleated RBC, to Low,n=0,0,0,1,1,0,1,0
0
0%
0
0%
0
0%
Nucleated RBC, to High,n=0,0,0,1,1,0,1,0
0
0%
0
0%
0
0%
RBC, to Low,n=1,2,7,5,6,4,10,6
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
RBC, to High,n=1,2,7,5,6,4,10,6
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Reticulocytes, to Low,n=1,2,7,4,2,2,7,5
0
0%
2
100%
5
71.4%
1
20%
2
33.3%
1
25%
2
20%
1
16.7%
Reticulocytes, to High,n=1,2,7,4,2,2,7,5
1
100%
1
50%
1
14.3%
0
0%
0
0%
0
0%
0
0%
0
0%
8. Primary Outcome
Title Number of Participants With Hematology Toxicity Grade Changes From Baseline
Description Blood samples were collected for analysis of hematology parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any grade increase worst-case on-therapy has been provided.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Hg increase,n=1,2,7,5,6,4,10,6
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Hg anemia,n=1,2,7,5,6,4,10,6
1
100%
2
100%
5
71.4%
4
80%
1
16.7%
2
50%
4
40%
3
50%
Lymph increase,n=1,2,7,4,2,2,10,6
0
0%
1
50%
1
14.3%
0
0%
0
0%
0
0%
3
30%
1
16.7%
Lymph decrease,n=1,2,7,4,2,2,10,6
1
100%
2
100%
2
28.6%
3
60%
1
16.7%
2
50%
5
50%
2
33.3%
Total Neu,n=1,2,7,4,2,2,10,6
1
100%
2
100%
1
14.3%
1
20%
1
16.7%
1
25%
1
10%
1
16.7%
Platelet,n=1,2,7,5,6,4,10,6
1
100%
1
50%
4
57.1%
3
60%
1
16.7%
2
50%
3
30%
3
50%
WBC,n=1,2,7,5,6,4,10,6
1
100%
2
100%
2
28.6%
4
80%
5
83.3%
1
25%
5
50%
1
16.7%
9. Primary Outcome
Title Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description SBP and DBP were measured after resting for 5 minutes in semi-supine position. Vital signs were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. An increase is defined as an increase in CTCAE grade relative to Baseline grade. For SBP Grade 0 (<120 millimeters of mercury [mmHg]), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (>=160 mmHg). For DBP Grade 0 (<80 mmHg), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (>=100 mmHg). Data for worst-case post Baseline is reported.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Only those participants with available data at the specified time points were analyzed (represented by n=X in category titles).
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
SBP,Any Grade Increase; n=1, 1, 3, 4, 6, 2, 5, 3
1
100%
1
50%
3
42.9%
4
80%
6
100%
2
50%
5
50%
3
50%
SBP,Increase to Grade 2;n=1, 1, 3, 4, 6, 2, 5, 3
1
100%
1
50%
1
14.3%
2
40%
2
33.3%
1
25%
4
40%
3
50%
SBP,Increase to Grade 3;n=1, 1, 3, 4, 6, 2, 5, 3
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
2
20%
0
0%
DBP,Any Grade Increase;n=1, 2, 3, 2, 4, 1, 3, 2
1
100%
2
100%
3
42.9%
2
40%
4
66.7%
1
25%
3
30%
2
33.3%
DBP,Increase to Grade 2;n=1, 2, 3, 2, 4, 1, 3, 2
1
100%
0
0%
1
14.3%
0
0%
2
33.3%
1
25%
2
20%
0
0%
DBP,Increase to Grade 3;n=1, 2, 3, 2, 4, 1, 3, 2
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
10. Primary Outcome
Title Part 1: Number of Participants With Change From Baseline in Heart Rate
Description Heart rate was measured after restings for 5 minutes in semi-supine position. Data for participants with heart rate decreased to < 60 beats per minute (bpm), normal or no change, increase to > 100 bpm. Data for worst post Baseline were reported.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Only those participants with available data at the specified time points were analyzed.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Decrease to <60
0
0%
0
0%
1
14.3%
0
0%
1
16.7%
0
0%
0
0%
0
0%
Change to Normal or No Change
0
0%
2
100%
1
14.3%
4
80%
4
66.7%
4
100%
5
50%
3
50%
Increase to >100
1
100%
0
0%
6
85.7%
1
20%
2
33.3%
0
0%
5
50%
3
50%
11. Primary Outcome
Title Part 1: Number of Participants With Change From Baseline in Temperature
Description Temperature was measured after resting for 5 minutes in semi-supine position. Data for participants with temperature decreased to <=35 Celsius, normal or no change, increase to >=38 Celsius at worst-case post Baseline is reported.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Decrease to <=35
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
0
0%
0
0%
Change to Normal or No Change
1
100%
2
100%
4
57.1%
4
80%
5
83.3%
4
100%
9
90%
6
100%
Increase to >=38
0
0%
0
0%
3
42.9%
1
20%
1
16.7%
0
0%
1
10%
0
0%
12. Primary Outcome
Title Part 1: Number of Participants With Change From Baseline in Respiratory Rate
Description Respiration rate was measured after resting for 5 minutes in semi-supine position. Data for worst case post-Baseline has been reported. Number of participants with respiratory rate decrease to <12 and increase to >25 has been reported.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Decrease to <12
0
0%
0
0%
0
0%
0
0%
0
0%
1
25%
0
0%
0
0%
Increase to >25
0
0%
0
0%
2
28.6%
0
0%
1
16.7%
0
0%
1
10%
0
0%
13. Primary Outcome
Title Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings
Description A single 12-lead ECG was performed in semi-recumbent or supine position after 5 minutes of rest for the participant. An ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals was used. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Only those participants with available data at the specified time points were analyzed.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Abnormal - not clinically significant
1
100%
2
100%
7
100%
4
80%
4
66.7%
2
50%
4
40%
6
100%
Abnormal - clinically significant
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
2
20%
1
16.7%
14. Primary Outcome
Title Part 1: Number of Participants With Abnormal Physical Examinations
Description Data for participants with abnormal physical examinations parameters was planned to be recorded.
Time Frame Median of 4 weeks of drug exposure

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. The data was not collected as it was not captured within the case report form (CRF).
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 0 0 0 0 0 0 0 0
15. Primary Outcome
Title Part 2: Objective Response Rate of Participants
Description Objective response rate defined as the percentage of participants who achievied complete remission (CR), partial remission (PR), CRp (as per CR but platelet count <100 x 10^9/L) and morphologic leukemia free state per response criteria. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
16. Secondary Outcome
Title Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration
Description Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric co-efficient of variation could not be calculated for a single participant.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
PK Population comprised of all treated participants for whom a PK sample was obtained and analyzed. Only those participants with available data at the specified time points were analyzed (represented by n=X in category titles).
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
AUC(0-t) n=1, 2, 7, 5, 6,4, 9,5
30.9457
(NA)
62.7579
(40.6)
211.1387
(34.8)
549.9557
(64.3)
738.1552
(77.6)
974.7759
(24.2)
97.6341
(38.8)
968.7825
(36.1)
AUC(0-inf); n=1, 2, 7, 5, 6,4, 8,5
36.8470
(NA)
72.7180
(31.4)
222.0837
(35.1)
600.6492
(61.9)
791.2295
(74.1)
1125.8508
(29.7)
105.4513
(41.7)
1101.4318
(41.0)
17. Secondary Outcome
Title Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric co-efficient could not be calculated for a single participant.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants with available data at the specified time points were analyzed.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 8 5
Geometric Mean (Geometric Coefficient of Variation) [Hour*nanograms per milliliter]
22.2630
(NA)
44.0692
(45.5)
169.5072
(35.1)
483.7209
(62.2)
638.4389
(70.3)
870.8045
(21.0)
80.2478
(48.4)
885.8174
(24.1)
18. Secondary Outcome
Title Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 15

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants with available data at the specified time points were analyzed.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 4 4 6 2 6 4
AUC (0-t)
22.0069
(NA)
82.6381
(31.2)
221.5336
(48.2)
692.8434
(62.3)
623.2032
(63.9)
1158.6530
(27.3)
132.0625
(38.4)
904.0276
(30.2)
AUC (0-tau)
37.6629
(NA)
82.8980
(31.5)
221.6595
(48.2)
699.1461
(62.3)
661.7915
(58.0)
1152.0895
(24.9)
142.6193
(35.0)
904.2889
(30.0)
19. Secondary Outcome
Title Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Day 1,n=1,2,7,5,6,4,9,5
4.0660
(NA)
7.5501
(34.2)
28.5460
(32.0)
65.5650
(59.8)
98.6033
(73.1)
134.8388
(12.8)
13.3889
(63.3)
142.8826
(28.6)
Day 15,n=1,2,4,4,6,2,6,4
4.3920
(NA)
11.5411
(60.1)
40.1989
(52.0)
83.2978
(32.9)
103.0141
(65.7)
224.2444
(17.7)
16.7684
(37.0)
144.6871
(25.4)
20. Secondary Outcome
Title Part 1: Apparent Terminal Phase Half-life (t½)
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 8 5
Geometric Mean (Geometric Coefficient of Variation) [Hours]
34.6647
(NA)
29.7715
(37.3)
19.6564
(15.9)
11.2045
(26.0)
12.4020
(26.5)
15.9502
(20.6)
14.9631
(38.9)
10.5340
(47.8)
21. Secondary Outcome
Title Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as standard deviation could not be calculated for a single participant.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Day 1, n=1, 2, 7, 5, 6, 4, 9, 5
0.983
0.7500
1.0000
0.9667
1.2750
0.6667
1.0000
1.0000
Day 15, n= 1, 2, 4, 4, 6, 2, 6, 4
1.0000
1.0000
0.7833
1.5833
0.8167
0.3833
0.9917
1.3000
22. Secondary Outcome
Title Part 1: Accumulation Ratio for GSK2879552
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Accumulation ratio was determined dividing AUC (0-tau) on Day 15 by AUC (0-tau) on Day 1. The ratio of accumulation of GSK2879552 was estimated by calculating the ratio of the geometric least squares (GLS) means of the AUC(0-tau) between Day 15 and Day 1 for all dose levels and the corresponding 90 percent confidence interval (CI) for each ratio.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 2 4 4 6 2 6 4
Number (90% Confidence Interval) [Ratio]
1.881
1.367
1.319
1.037
1.388
1.750
1.073
23. Secondary Outcome
Title Part 1:Time Invariance
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. The time invariance of GSK2879552 was estimated by calculating the ratio of the GLS means of the AUC (0-tau) between Day 15 and Day 1 for all dose levels and the corresponding 90 percent CI for each ratio.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15

Outcome Measure Data

Analysis Population Description
PK Population.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 0 2 4 4 6 2 6 4
Number (90% Confidence Interval) [Ratio]
1.140
1.030
1.042
0.836
1.167
1.346
0.845
24. Secondary Outcome
Title Part 1:Percentage of Participants With Objective Response
Description Objective response rate is defined as the percentage of participants who achieved CR, PR, as per CR but platelet count <100 x 10^9/L and morphologic leukemia free state per response criteria.
Time Frame Median of 4 weeks drug response

Outcome Measure Data

Analysis Population Description
All Treated Subjects.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD.
Measure Participants 1 2 7 5 6 4 10 6
Number (95% Confidence Interval) [Percentage of Participants]
0
0%
0
0%
0
0%
0
0%
17
283.3%
0
0%
10
100%
0
0%
25. Secondary Outcome
Title Part 1: AUC(0-t), AUC (0-tau) and AUC(0-inf) of ATRA
Description Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1and Day 15

Outcome Measure Data

Analysis Population Description
PK Population. Plasma samples were not quantifiable for ATRA at all end points and hence the PK parameters could not be derived.
Arm/Group Title Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day
Arm/Group Description Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day.
Measure Participants 0
26. Secondary Outcome
Title Part 1: Cmax of ATRA
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15

Outcome Measure Data

Analysis Population Description
PK Population. Plasma samples were not quantifiable for ATRA at all end points and hence the PK parameters could not be derived.
Arm/Group Title Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day
Arm/Group Description Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day.
Measure Participants 0
27. Secondary Outcome
Title Part 1: Apparent Terminal Phase Half-life (t½) of ATRA
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15

Outcome Measure Data

Analysis Population Description
PK Population. Plasma samples were not quantifiable for ATRA at all end points and hence the PK parameters could not be derived.
Arm/Group Title Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day
Arm/Group Description Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day.
Measure Participants 0
28. Secondary Outcome
Title Part 1: Time of Occurrence of Cmax (Tmax) of ATRA
Description Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time Frame Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15

Outcome Measure Data

Analysis Population Description
PK Population. Plasma samples were not quantifiable for ATRA at all end points and hence the PK parameters could not be derived.
Arm/Group Title Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day
Arm/Group Description Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day.
Measure Participants 0
29. Secondary Outcome
Title Part 2: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Description An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
30. Secondary Outcome
Title Part 2: Number of Participants With AE Leading to Dose Reductions or Delays
Description The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
31. Secondary Outcome
Title Part 2: Number of Participants With Withdrawals Due to Toxicities
Description Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
32. Secondary Outcome
Title Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters
Description Data was not collected for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
33. Secondary Outcome
Title Part 2: Number of Participants With Abnormal Hematology Parameters
Description Data was not collected for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
34. Secondary Outcome
Title Part 2: Number of Participants With Abnormal Vital Signs
Description Data was not collected for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
35. Secondary Outcome
Title Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
36. Secondary Outcome
Title Part 2: Number of Participants With Abnormal Physical Examinations
Description This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
37. Secondary Outcome
Title Part 2: Clearance (CL) of GSK2879552 for Part 2
Description This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Day 1 (pre-dose, 0.5 and 3 hours post dose), Days 4, 8 (pre-dose), Day 15 (pre-dose, 0.5, 1, 4, 6 hours), Weeks 4, 5, 6, 7, 8 and every 4 weeks up to Week 48

Outcome Measure Data

Analysis Population Description
PK Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
38. Secondary Outcome
Title Part 2: Volume of Distribution of GSK2879552 for Part 2
Description This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Day 1 (pre-dose, 0.5 and 3 hours post dose), Days 4, 8 (pre-dose), Day 15 (pre-dose, 0.5, 1, 4, 6 hours), Weeks 4, 5, 6, 7, 8 and every 4 weeks up to Week 48

Outcome Measure Data

Analysis Population Description
PK Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description All Participants. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Measure Participants 0
39. Secondary Outcome
Title Number of Participants With Abnormal Covariates: Part 2
Description This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Participants. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
40. Secondary Outcome
Title Duration of Response: Part 2
Description This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Participants. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
41. Secondary Outcome
Title Time to Time to Response: Part 2
Description This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Participants. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0
42. Secondary Outcome
Title Progression-free Survival: Part 2
Description This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame Up to 14 months

Outcome Measure Data

Analysis Population Description
All Participants. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Arm/Group Title Part 2: Expansion Cohort
Arm/Group Description In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
Measure Participants 0

Adverse Events

Time Frame Adverse events were collected from start of the study up to 3 years
Adverse Event Reporting Description All Treated Subjects Population was used to collect adverse events. AEs and SAEs were not collected in Part 2 of the study as no participants were enrolled due to early termination during Part 1.
Arm/Group Title Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion Part 2: Expansion Cohort
Arm/Group Description Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m^2/day. Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD. In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA.
All Cause Mortality
Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion Part 2: Expansion Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/5 (0%) 3/6 (50%) 1/4 (25%) 2/10 (20%) 1/6 (16.7%) 0/0 (NaN)
Serious Adverse Events
Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion Part 2: Expansion Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/1 (100%) 2/2 (100%) 7/7 (100%) 5/5 (100%) 6/6 (100%) 3/4 (75%) 8/10 (80%) 5/6 (83.3%) 0/0 (NaN)
Blood and lymphatic system disorders
Febrile neutropenia 1/1 (100%) 2 2/2 (100%) 6 3/7 (42.9%) 5 3/5 (60%) 6 3/6 (50%) 3 1/4 (25%) 1 4/10 (40%) 4 3/6 (50%) 4 0/0 (NaN) 0
Anaemia 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Leukocytosis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Thrombocytopenia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Cardiac disorders
Cardiomyopathy 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Gastrointestinal disorders
Gastric haemorrhage 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Nausea 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Oral pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Pancreatitis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Toothache 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Vomiting 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
General disorders
Pyrexia 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Infections and infestations
Cellulitis 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Pneumonia 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Anorectal cellulitis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Escherichia sepsis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Influenza 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Klebsiella bacteraemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Lung infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Pseudomonal bacteraemia 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Parainfluenzae virus infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Pneumonia respiratory syncytial viral 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Pulmonary mycosis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Septic shock 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Soft tissue infection 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Upper respiratory tract infection 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Viral infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Injury, poisoning and procedural complications
Subdural haematoma 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Clavicle fracture 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Fall 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Subarachnoid haemorrhage 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Investigations
Alanine aminotransferase increased 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Troponin I increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Musculoskeletal and connective tissue disorders
Arthralgia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 2 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Bone pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Nervous system disorders
Cognitive disorder 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Encephalopathy 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Psychiatric disorders
Delirium 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hallucination 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Renal and urinary disorders
Acute kidney injury 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hypoxia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Pleural effusion 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Vascular disorders
Haematoma 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Other (Not Including Serious) Adverse Events
Part 1:GSK2879552 1mg QD Part 1: GSK2879552 2mg QD Part 1: GSK2879552 4mg QD Part 1: GSK2879552 8mg QD Part 1: GSK2879552 12mg QD Part 1: GSK2879552 20mg QD Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Part 1: GSK2879552 20mg QD PK/PD Expansion Part 2: Expansion Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/1 (100%) 2/2 (100%) 6/7 (85.7%) 5/5 (100%) 6/6 (100%) 4/4 (100%) 10/10 (100%) 6/6 (100%) 0/0 (NaN)
Blood and lymphatic system disorders
Anaemia 1/1 (100%) 1 1/2 (50%) 1 1/7 (14.3%) 1 2/5 (40%) 2 1/6 (16.7%) 1 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Febrile neutropenia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 2/4 (50%) 2 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Thrombocytopenia 0/1 (0%) 0 1/2 (50%) 1 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hyperleukocytosis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Leukocytosis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Neutropenia 1/1 (100%) 1 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Cardiac disorders
Sinus tachycardia 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Tachycardia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Atrial fibrillation 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Pericardial effusion 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Sinus bradycardia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Ear and labyrinth disorders
Hypoacusis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Deafness 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Deafness bilateral 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Deafness neurosensory 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Ear discomfort 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 2 0/6 (0%) 0 0/0 (NaN) 0
Excessive cerumen production 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Endocrine disorders
Hyperthyroidism 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Eye disorders
Conjunctival haemorrhage 1/1 (100%) 1 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Dry eye 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Eye haematoma 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Eye swelling 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Photophobia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Visual impairment 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Gastrointestinal disorders
Nausea 1/1 (100%) 1 0/2 (0%) 0 5/7 (71.4%) 6 3/5 (60%) 3 2/6 (33.3%) 4 1/4 (25%) 1 6/10 (60%) 6 1/6 (16.7%) 2 0/0 (NaN) 0
Vomiting 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 2/5 (40%) 5 4/6 (66.7%) 6 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Constipation 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 2/6 (33.3%) 2 1/4 (25%) 1 4/10 (40%) 4 1/6 (16.7%) 1 0/0 (NaN) 0
Diarrhoea 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 2 2/5 (40%) 3 0/6 (0%) 0 1/4 (25%) 1 4/10 (40%) 4 0/6 (0%) 0 0/0 (NaN) 0
Stomatitis 0/1 (0%) 0 1/2 (50%) 1 1/7 (14.3%) 1 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Angina bullosa haemorrhagica 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Mouth haemorrhage 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 1/5 (20%) 1 1/6 (16.7%) 1 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Mouth ulceration 0/1 (0%) 0 0/2 (0%) 0 2/7 (28.6%) 2 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Anal incontinence 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Gingival bleeding 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 1 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Abdominal distension 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Abdominal pain 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Oral pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 2/4 (50%) 2 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Toothache 0/1 (0%) 0 1/2 (50%) 1 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Ascites 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Chapped lips 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Dental discomfort 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Dry mouth 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Dyspepsia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Gastric ulcer 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Gastrointestinal haemorrhage 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Glossodynia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Haemorrhoids 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Lip swelling 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Oral disorder 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Rectal haemorrhage 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Tongue ulceration 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
General disorders
Fatigue 1/1 (100%) 1 2/2 (100%) 2 2/7 (28.6%) 2 2/5 (40%) 2 3/6 (50%) 3 1/4 (25%) 1 3/10 (30%) 3 0/6 (0%) 0 0/0 (NaN) 0
Localised oedema 0/1 (0%) 0 0/2 (0%) 0 2/7 (28.6%) 3 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 2 2/6 (33.3%) 2 0/0 (NaN) 0
Oedema peripheral 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 2 1/4 (25%) 1 2/10 (20%) 2 1/6 (16.7%) 1 0/0 (NaN) 0
Pyrexia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 3/6 (50%) 3 0/4 (0%) 0 2/10 (20%) 2 1/6 (16.7%) 1 0/0 (NaN) 0
Non-cardiac chest pain 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 3/10 (30%) 4 0/6 (0%) 0 0/0 (NaN) 0
Pain 0/1 (0%) 0 0/2 (0%) 0 2/7 (28.6%) 2 0/5 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 1 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Influenza like illness 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 2 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Mucosal inflammation 0/1 (0%) 0 1/2 (50%) 1 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Chills 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Catheter site erythema 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Catheter site pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Catheter site vesicles 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Cyst 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Catheter site haemorrhage 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Face oedema 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Facial pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hypothermia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Nodule 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Oedema 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hepatobiliary disorders
Cholelithiasis 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Infections and infestations
Device related infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Cellulitis 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 2/5 (40%) 2 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Lung infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Oral herpes 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Sepsis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Staphylococcal infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Urinary tract infection 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Aspergillus infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Bacteraemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Clostridium difficile infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Conjunctivitis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hepatitis B 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Herpes zoster 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Localised infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Pneumonia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Pulmonary mycosis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Respiratory tract infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Tooth infection 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Vaginal abscess 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Wound infection 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Injury, poisoning and procedural complications
Fall 0/1 (0%) 0 1/2 (50%) 1 1/7 (14.3%) 1 1/5 (20%) 1 1/6 (16.7%) 1 1/4 (25%) 1 3/10 (30%) 3 1/6 (16.7%) 2 0/0 (NaN) 0
Infusion related reaction 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 2 1/6 (16.7%) 1 1/4 (25%) 1 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Contusion 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 2/6 (33.3%) 3 0/0 (NaN) 0
Laceration 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Skin abrasion 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 4 0/6 (0%) 0 0/0 (NaN) 0
Transfusion reaction 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 4 0/6 (0%) 0 0/0 (NaN) 0
Investigations
International normalised ratio increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Platelet count decreased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 2/5 (40%) 3 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Blood creatinine increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Neutrophil count decreased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 2 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
White blood cell count decreased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 2 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Alanine aminotransferase increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
White blood cell count increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Activated partial thromboplastin time prolonged 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Aspartate aminotransferase increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/1 (100%) 1 0/6 (0%) 0 0/0 (NaN) 0
Blood alkaline phosphatase increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Blood bilirubin increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Lymphocyte count increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Clostridium test positive 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Oxygen saturation decreased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Vitamin B12 decreased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Troponin I increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Troponin increased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Metabolism and nutrition disorders
Hypokalaemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Decreased appetite 0/1 (0%) 0 1/2 (50%) 1 2/7 (28.6%) 2 3/5 (60%) 3 1/6 (16.7%) 2 1/4 (25%) 1 3/10 (30%) 3 0/6 (0%) 0 0/0 (NaN) 0
Hypophosphataemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 3/5 (60%) 3 2/6 (33.3%) 2 1/4 (25%) 1 4/10 (40%) 5 1/6 (16.7%) 4 0/0 (NaN) 0
Hypomagnesaemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 2/5 (40%) 2 0/6 (0%) 0 1/4 (25%) 1 2/10 (20%) 2 2/6 (33.3%) 2 0/0 (NaN) 0
Fluid overload 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 3/10 (30%) 3 1/6 (16.7%) 1 0/0 (NaN) 0
Hyperglycaemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Hypocalcaemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 2/6 (33.3%) 2 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hyponatraemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Acidosis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Fluid retention 0/1 (0%) 0 1/2 (50%) 1 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hyperkalaemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hypernatraemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hypertriglyceridaemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Hypoalbuminaemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hypoglycaemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Pseudohyponatraemia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Musculoskeletal and connective tissue disorders
Arthralgia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 1 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Muscular weakness 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 2/6 (33.3%) 2 0/0 (NaN) 0
Bone pain 1/1 (100%) 1 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Arthritis 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Back pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Musculoskeletal pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Pain in extremity 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Joint range of motion decreased 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Joint stiffness 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Limb discomfort 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Musculoskeletal chest pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Nervous system disorders
Dizziness 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 1/4 (25%) 1 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Headache 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 2 0/4 (0%) 0 2/10 (20%) 2 1/6 (16.7%) 2 0/0 (NaN) 0
Lethargy 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 2/6 (33.3%) 2 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Disturbance in attention 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Syncope 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Arachnoid web 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Cognitive disorder 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Dysarthria 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Dysgeusia 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Hypoaesthesia 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Loss of consciousness 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Presyncope 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Sciatica 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Serotonin syndrome 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Psychiatric disorders
Confusional state 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 4/10 (40%) 4 1/6 (16.7%) 1 0/0 (NaN) 0
Insomnia 1/1 (100%) 1 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Agitation 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Anxiety 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Depressed mood 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Delirium 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Hallucination 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Renal and urinary disorders
Urinary incontinence 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Acute kidney injury 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Pollakiuria 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Incontinence 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Urinary retention 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Reproductive system and breast disorders
Penile haemorrhage 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Scrotal disorder 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Respiratory, thoracic and mediastinal disorders
Epistaxis 0/1 (0%) 0 1/2 (50%) 1 1/7 (14.3%) 1 0/5 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 1 3/10 (30%) 5 1/6 (16.7%) 1 0/0 (NaN) 0
Dyspnoea 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 1/5 (20%) 1 2/6 (33.3%) 2 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Hypoxia 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 2/6 (33.3%) 2 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Nasal congestion 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Pleural effusion 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 1/6 (16.7%) 1 0/0 (NaN) 0
Oropharyngeal pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 1/4 (25%) 1 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Tachypnoea 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Haemoptysis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Lower respiratory tract congestion 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Nasal dryness 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Pleuritic pain 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Pneumonitis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Productive cough 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Cough 0/1 (0%) 0 1/2 (50%) 1 1/7 (14.3%) 1 1/5 (20%) 1 4/6 (66.7%) 6 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Wheezing 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 1/0 (Infinity) 1
Skin and subcutaneous tissue disorders
Petechiae 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 1/5 (20%) 1 3/6 (50%) 3 0/4 (0%) 0 2/10 (20%) 2 1/6 (16.7%) 1 0/0 (NaN) 0
Dry skin 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 1 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Skin lesion 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 1/5 (20%) 2 0/6 (0%) 0 1/4 (25%) 1 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Pruritus 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/10 (10%) 1 1/6 (16.7%) 1 0/0 (NaN) 0
Psoriasis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/6 (33.3%) 2 0/0 (NaN) 0
Rash pruritic 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Alopecia 0/1 (0%) 0 0/2 (0%) 0 1/7 (14.3%) 1 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Blister 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 2 0/6 (0%) 0 0/0 (NaN) 0
Blood blister 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Decubitus ulcer 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/6 (16.7%) 1 0/0 (NaN) 0
Hyperhidrosis 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Skin exfoliation 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Swelling face 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/6 (0%) 0 0/0 (NaN) 0
Urticaria 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Rash 1/1 (100%) 1 1/2 (50%) 1 2/7 (28.6%) 2 0/5 (0%) 0 2/6 (33.3%) 2 1/4 (25%) 1 2/10 (20%) 2 0/6 (0%) 0 0/0 (NaN) 0
Surgical and medical procedures
Endodontic procedure 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0
Vascular disorders
Hypotension 0/1 (0%) 0 1/2 (50%) 1 2/7 (28.6%) 2 2/5 (40%) 2 2/6 (33.3%) 2 1/4 (25%) 1 3/10 (30%) 4 2/6 (33.3%) 2 0/0 (NaN) 0
Haematoma 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/6 (33.3%) 2 0/0 (NaN) 0
Haemorrhage 0/1 (0%) 0 0/2 (0%) 0 0/7 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/6 (0%) 0 0/0 (NaN) 0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email GSKClinicalSupportHD@gsk.com
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02177812
Other Study ID Numbers:
  • 200200
First Posted:
Jun 30, 2014
Last Update Posted:
Jun 28, 2019
Last Verified:
Apr 1, 2019