Brief Summary
Eltrombopag olamine (SB-497115-GR) is an orally bioavailable, small molecule thrombopoietin receptor agonist that may be beneficial in medical disorders associated with thrombocytopenia. Eltrombopag has been shown to increase platelet counts in patients with thrombocytopenia from various etiologies (Idiopathic thrombocytopenic purpura \[ITP\], liver disease, aplastic anemia and chemotherapy induced thrombocytopenia). Approximately 350 subjects will be randomized in a 1:1 ratio (175 into the eltrombopag arm and 175 into the placebo arm). Approximately 55 subjects will be enrolled into the azacitidine. Subjects with intermediate-1, intermediate-2 or high risk MDS by IPSS, and baseline platelet count of \<75 Giga (10\^9) per liter (Gi/L) will only be enrolled. This is a randomized, double-blind, parallel group, placebo-controlled study designed to explore the platelet supportive care effects of eltrombopag versus placebo in combination with the standard of care hypomethylating agent, azacitidine. The primary objective of this study is to determine the effect of eltrombopag versus placebo on the proportion of subjects who are platelet transfusion free during the first 4 cycles of azacitidine therapy. Key secondary endpoints include overall survival, disease response, and disease progression.
Brief Title
A Study of Eltrombopag or Placebo in Combination With Azacitidine in Subjects With International Prognostic Scoring System (IPSS) Intermediate-1, Intermediate-2 or High-risk Myelodysplastic Syndromes (MDS)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Thrombocytopaenia
Eligibility Criteria
Inclusion Criteria:
* Age \>=18 years (For subjects in Taiwan, Age \>= 20 years)
* MDS by World Health Organization (WHO) or French-American-British (FAB) classification
* Intermediate 1, intermediate 2 or high risk MDS by IPSS
* At least one platelet count \< 75 Gi/L
* Eastern Cooperative Oncology Group (ECOG) Status 0-2
* Adequate baseline organ function defined by the criteria below: total bilirubin =\< 1.5x the upper limit of normal (ULN) except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect \[haemolytic\] bilirubin in the absence of alanine aminotransferase \[ALT\] abnormality); ALT =\< 2.5xULN; creatinine =\< 2.5xULN
* Subjects with a corrected QT interval (QTc) \<450 milliseconds (msec) or \<480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period
* Subject is able to understand and comply with protocol requirements and instructions
* Subject has signed and dated informed consent
* Women must be either of non-child bearing potential, or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study
* Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception during the study and for 3 months 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 time of randomization until 16 weeks after the last dose of study treatment
* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Exclusion Criteria:
* Previous treatment with hypomethylating agent or induction chemotherapy for MDS
* Proliferative type chronic myelomonocytic leukemia with white blood cell count \>12 Gi/L at any time during the 28 days before Day 1
* History of treatment with eltrombopag, romiplostim or other thrombopoietin receptor (TPO-R) agonists
* Previous allogeneic stem-cell transplantation
* Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator
* Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of investigational product (eltrombopag/placebo)
* Active and uncontrolled infections, including hepatitis B or C
* Human Immunodeficiency Virus (HIV) infection
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or its excipient, or azacitidine, that contraindicates the subjects' participation
* Pregnant or lactating female
* Any serious and/or unstable pre-existing medical condition (including any advanced malignancy other than the disease under study), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures
* French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days
* Age \>=18 years (For subjects in Taiwan, Age \>= 20 years)
* MDS by World Health Organization (WHO) or French-American-British (FAB) classification
* Intermediate 1, intermediate 2 or high risk MDS by IPSS
* At least one platelet count \< 75 Gi/L
* Eastern Cooperative Oncology Group (ECOG) Status 0-2
* Adequate baseline organ function defined by the criteria below: total bilirubin =\< 1.5x the upper limit of normal (ULN) except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect \[haemolytic\] bilirubin in the absence of alanine aminotransferase \[ALT\] abnormality); ALT =\< 2.5xULN; creatinine =\< 2.5xULN
* Subjects with a corrected QT interval (QTc) \<450 milliseconds (msec) or \<480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period
* Subject is able to understand and comply with protocol requirements and instructions
* Subject has signed and dated informed consent
* Women must be either of non-child bearing potential, or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study
* Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception during the study and for 3 months 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 time of randomization until 16 weeks after the last dose of study treatment
* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Exclusion Criteria:
* Previous treatment with hypomethylating agent or induction chemotherapy for MDS
* Proliferative type chronic myelomonocytic leukemia with white blood cell count \>12 Gi/L at any time during the 28 days before Day 1
* History of treatment with eltrombopag, romiplostim or other thrombopoietin receptor (TPO-R) agonists
* Previous allogeneic stem-cell transplantation
* Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator
* Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of investigational product (eltrombopag/placebo)
* Active and uncontrolled infections, including hepatitis B or C
* Human Immunodeficiency Virus (HIV) infection
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or its excipient, or azacitidine, that contraindicates the subjects' participation
* Pregnant or lactating female
* Any serious and/or unstable pre-existing medical condition (including any advanced malignancy other than the disease under study), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures
* French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days
Inclusion Criteria
Inclusion Criteria:
* Age \>=18 years (For subjects in Taiwan, Age \>= 20 years)
* MDS by World Health Organization (WHO) or French-American-British (FAB) classification
* Intermediate 1, intermediate 2 or high risk MDS by IPSS
* At least one platelet count \< 75 Gi/L
* Eastern Cooperative Oncology Group (ECOG) Status 0-2
* Adequate baseline organ function defined by the criteria below: total bilirubin =\< 1.5x the upper limit of normal (ULN) except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect \[haemolytic\] bilirubin in the absence of alanine aminotransferase \[ALT\] abnormality); ALT =\< 2.5xULN; creatinine =\< 2.5xULN
* Subjects with a corrected QT interval (QTc) \<450 milliseconds (msec) or \<480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period
* Subject is able to understand and comply with protocol requirements and instructions
* Subject has signed and dated informed consent
* Women must be either of non-child bearing potential, or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study
* Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception during the study and for 3 months 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 time of randomization until 16 weeks after the last dose of study treatment
* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
* Age \>=18 years (For subjects in Taiwan, Age \>= 20 years)
* MDS by World Health Organization (WHO) or French-American-British (FAB) classification
* Intermediate 1, intermediate 2 or high risk MDS by IPSS
* At least one platelet count \< 75 Gi/L
* Eastern Cooperative Oncology Group (ECOG) Status 0-2
* Adequate baseline organ function defined by the criteria below: total bilirubin =\< 1.5x the upper limit of normal (ULN) except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect \[haemolytic\] bilirubin in the absence of alanine aminotransferase \[ALT\] abnormality); ALT =\< 2.5xULN; creatinine =\< 2.5xULN
* Subjects with a corrected QT interval (QTc) \<450 milliseconds (msec) or \<480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period
* Subject is able to understand and comply with protocol requirements and instructions
* Subject has signed and dated informed consent
* Women must be either of non-child bearing potential, or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study
* Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception during the study and for 3 months 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 time of randomization until 16 weeks after the last dose of study treatment
* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Gender
All
Gender Based
false
Keywords
thrombocytopenia
myelodysplastic syndromes
MDS
thrombopoietin
azacitidine
Eltrombopag
myelodysplastic syndromes (MDS)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02158936
Org Class
Industry
Org Full Name
Novartis
Org Study Id
112121
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Double-blind, Placebo-controlled, Phase III, Multi-centre Study of Eltrombopag or Placebo in Combination With Azacitidine in Subjects With IPSS Intermediate-1, Intermediate 2 and High-risk Myelodysplastic Syndromes (MDS) SUPPORT: A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine
Primary Outcomes
Outcome Description
A subject is defined as being platelet transfusion independent if they received no platelet transfusions within the first 4 cycles of treatment with azacitidine. Subjects who died or withdrew from investigational product within the first four cycles were treated as failures (i.e. not transfusion independent) in the analysis
Outcome Measure
Number of Participants Who Were Platelet Transfusion Independent During Cycles 1-4 of Azacitidine Therapy
Outcome Time Frame
4 cycles (Cycle = 28 days)
Secondary Outcomes
Outcome Description
Overall survival is defined as the time from randomization until death due to any cause and deaths have been presented. Subjects still alive at the time of the analysis and subjects who have withdrawn from the study will be censored at the time of last contact
Outcome Time Frame
Randomization until death or end of study, approximately 2 years
Outcome Measure
Overall Survival (OS)
Outcome Description
Progression-free survival, defined as the time from randomization until either disease progression or death. The modified 2006 IWG criteria for MDS used for progression assessment For patients with: Less than 5% BM blasts: ≥ 50% increase in blasts to \> 5% blasts; 5% - \<10% BM blasts: ≥ 50% increase to \> 10% blasts; 10% - \<20% BM blasts: ≥ 50% increase to \> 20% blasts; 20% - 30% BM blasts: ≥ 50% increase to \> 30% blasts
Outcome Time Frame
First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Outcome Measure
Summary of Progression Free Survival From Investigator Assessment (ITT)
Outcome Description
Progression-free survival, defined as the time from randomization until either disease progression or death. The modified 2006 IWG criteria for MDS used for progression assessment For patients with:
Less than 5% BM blasts: ≥ 50% increase in blasts to \> 5% blasts; 5% - \<10% BM blasts: ≥ 50% increase to \> 10% blasts; 10% - \<20% BM blasts: ≥ 50% increase to \> 20% blasts; 20% - 30% BM blasts: ≥ 50% increase to \> 30% blasts
Less than 5% BM blasts: ≥ 50% increase in blasts to \> 5% blasts; 5% - \<10% BM blasts: ≥ 50% increase to \> 10% blasts; 10% - \<20% BM blasts: ≥ 50% increase to \> 20% blasts; 20% - 30% BM blasts: ≥ 50% increase to \> 30% blasts
Outcome Time Frame
First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Outcome Measure
Summary of Progression Free Survival From Central Review (ITT)
Outcome Description
Progression to AML in MDS patients with baseline bone marrow blast \< 20% was defined as meeting definition of disease progression according to the modified 2006 IWG response criteria for MDS with the additional requirement that bone marrow blast or peripheral blast increases from \< 20% at baseline to ≥ 20% postbaseline. Progression assessment For patients with:
Less than 5% BM blasts: ≥ 50% increase in blasts to \> 5% blasts; 5% - \<10% BM blasts: ≥ 50% increase to \> 10% blasts; 10% - \<20% BM blasts: ≥ 50% increase to \> 20% blasts; 20% - 30% BM blasts: ≥ 50% increase to \> 30% blasts
Less than 5% BM blasts: ≥ 50% increase in blasts to \> 5% blasts; 5% - \<10% BM blasts: ≥ 50% increase to \> 10% blasts; 10% - \<20% BM blasts: ≥ 50% increase to \> 20% blasts; 20% - 30% BM blasts: ≥ 50% increase to \> 30% blasts
Outcome Time Frame
First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Outcome Measure
Summary of AML Progression From Investigator Assessment and Central Review (ITT)
Outcome Description
Best disease response is categorized as complete remission (CR), partial remission (PR), or marrow CR, stable disease, disease progression, or as non-evaluable; according to modified 2006 International Working Group (IWG) criteria for MDS
Outcome Time Frame
At end of Cycle 6 (cycle=28 days) or end of therapy, whichever came first
Outcome Measure
Best Disease Response From Investigator Assessment (ITT)
Outcome Description
Best disease response is categorized as complete remission (CR), partial remission (PR), or marrow CR, stable disease, disease progression, or as non-evaluable; according to modified 2006 International Working Group (IWG) criteria for MDS
Outcome Time Frame
At end of Cycle 6 (cycle=28 days) or end of therapy, whichever came first
Outcome Measure
Best Disease Response From Central Review (ITT)
Outcome Description
HI based on the modified IWG criteria for MDS. HI - Platelets (BL \<100Gi/L), response criteria= BL \<20: increase to\>20 and 100% at least for 56 days or BL \>=20: absolute increase of \>=30. HI - Neutrophils (BL \<1.0 Gi/L), response criteria=100% increase and an absolute increase \>0.5 Gi/L over BL for at least 56 days. HI-Hemoglobin (BL \<g/dL), response criteria=Hgb increase by \>=1.5 g/dL over BL, RBC transfusions(given for Hgb\<=9.0) reduced by \>=4 per 8w from BL
Outcome Time Frame
From Day 1 to 4-week follow-up (samples collected weekly in Cycle 1, Days 1 and 15 in Cycles 2-6 and Day 1 of Cycles >=7)
Outcome Measure
Hematologic Improvement (HI) in Platelets, Neutrophils, and Hemoglobin Based on the Modified IWG Criteria for MDS (ITT)
Outcome Description
Platelet transfusion independence is defined for each cycle as the number of participants who continue to the end of a cycle without requiring a platelet transfusion
Outcome Time Frame
From Day 1 to end of study treatment up to approximately 2 years
Outcome Measure
Number of Participants Who Were Platelet Transfusion Independent (ITT Set)
Outcome Description
Bleeding will be assessed by recording AEs or serious adverse events (SAEs) as graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Outcome Time Frame
From Day 1 to 4-week follow-up up to approximately 2 years
Outcome Measure
Bleeding Adverse Events (AEs) >= Grade 3
Outcome Description
The proportion of subjects with any delay, reduction or interruption in dosage of Azacitidine excluding those for non-medical reasons will be analyzed
Outcome Time Frame
From Day 1 to 4-week follow-up up to approximately 2 years
Outcome Measure
Number of of Subjects With Azacitidine Dose Delays, Dose Reductions, Interruptions
Outcome Description
The EQ-5D is a general health status and health utility measure which captures 5 dimensions of health state: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. (EQ-5D is a trademark of the Stichting EuroQol Group) . C=cycle, D=Day
Outcome Time Frame
From Day 1 to 4-week follow-up up to approximately 2 years
Outcome Measure
Response Levels in All Domains of Euroquol-5 Dimensions of Health, 3 Response Levels (EQ-5D-3L™)
Outcome Description
The FACIT-Fatigue subscale measures severity and impact of fatigue on functioning and Health Related QoL experienced in the past 7 days. Scale is a 13 item measure of fatigure. Items are scored on a 0-4 response scale ranging from "not at all" to "very much so". All items are summed to create a single fatigure score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatiigue (The FACIT Fatigue Scale is owned by David Cella, Ph.D.)
Outcome Time Frame
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Outcome Measure
Functional Assessment of Chronic Disease Therapy-fatigue Subscale (FACIT-Fatigue) (ITT)
Outcome Description
MRU data will be collected for each subject. Events corresponding to unscheduled (not scheduled per protocol) hospitalizations
Outcome Time Frame
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Outcome Measure
Medical Resource Utilization (MRU): Event -Hospitalizations Inpatient and Outpatient
Outcome Description
MRU data will be collected for each subject. Events corresponding to unscheduled (not scheduled per protocol) hospitalizations, office visits including consultations, laboratory and diagnostic tests (lab results, imaging etc.), and procedures prior to therapy initiation and during therapy will be collected
Outcome Time Frame
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Outcome Measure
Medical Resource Utilization (MRU): Event and Use of Site Specific Medical Resources - Non-study Laboratory Tests
Outcome Description
MRU data will be collected for each subject. Events corresponding to unscheduled (not scheduled per protocol) hospitalizations, office visits including consultations, laboratory and diagnostic tests (lab results, imaging etc.), and procedures prior to therapy initiation and during therapy will be collected
Outcome Time Frame
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Outcome Measure
Medical Resource Utilization (MRU): Use of Site Specific Medical Resources
Outcome Description
Eltrombopag concentrations were analyzed using a population PK model along with data from other studies in healthy volunteers and in patients with MDS and/or AML. Post-hoc PK parameters were derived. Only patients from this study were included (163)
Outcome Time Frame
Cycle 1, Week 2: Pre-dose, 1.5 and 3 hour post dose; Cycle 1, Week 3: 4, 5.5, and 7 hours post dose
Outcome Measure
Summary of Post-Hoc Estimates of Steady-state Eltrombopag Cmax and Cmin Pharmacokinetic Parameters for a 50 mg Dose
Outcome Description
Eltrombopag concentrations were analyzed using a population PK model along with data from other studies in healthy volunteers and in patients with MDS and/or AML. Post-hoc PK parameters were derived. Only patients from this study were included (163)
Outcome Time Frame
Cycle 1, Week 2: Pre-dose, 1.5 and 3 hour post dose; Cycle 1, Week 3: 4, 5.5, and 7 hours post dose
Outcome Measure
Summary of Post-Hoc Estimates of Steady-state Eltrombopag AUC0 Infinity Pharmacokinetic Parameters for a 50 mg Dose
Outcome Description
An analysis of variance (ANOVA) on AUC0-infinity. The PK parameters were log transformed prior to analysis. The model included treatment as a fixed effect. Point estimates and their associated 90% CI were constructed for the differences in PK parameter values. The point estimates and their associated 90% CI were then back transformed to provide point estimates and 90% CI for the azacitidine + eltrombopag:azacitidine + placebo PK parameter ratios.
Outcome Time Frame
Cycle 2 Day 1: Pre-dose, 15 min, 0.5, 1, 2 and 4 hr post dose
Outcome Measure
AUC0-infinity -Pharmacokinetic(s) Parameter of Azacitidine
Outcome Description
An analysis of variance (ANOVA) on Cmax . The PK parameters were log transformed prior to analysis. The model included treatment as a fixed effect. Point estimates and their associated 90% CI were constructed for the differences in PK parameter values. The point estimates and their associated 90% CI were then back transformed to provide point estimates and 90% CI for the azacitidine + ltrombopag:azacitidine + placebo PK parameter ratios.
Outcome Time Frame
Cycle 2 Day 1: Pre-dose, 15 min, 0.5, 1, 2 and 4 hr post dose
Outcome Measure
Cmax -Pharmacokinetic Parameter of Azacitidine
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Amit Verma
Investigator Email
amit.verma@einsteinmed.org
Investigator Phone
718-405-8505 / 718-904-2900
Categories Mesh Debug
Blood & Bone Marrow Cancers --- MYELODYSPLASTIC SYNDROMES
Blood Disorders --- BLOOD PLATELET DISORDERS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- BONE MARROW DISEASES
MeSH Terms
THROMBOCYTOPENIA
MYELODYSPLASTIC SYNDROMES
JACOBS SYNDROME
BLOOD PLATELET DISORDERS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
CYTOPENIA
BONE MARROW DISEASES
ELTROMBOPAG
AZACITIDINE
COUNTERFEIT DRUGS
AZA COMPOUNDS
ORGANIC CHEMICALS
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
RIBONUCLEOSIDES
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS