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| ID | Type | Description | Link |
|---|---|---|---|
| MK-1775-008 | Other Identifier | Merck Protocol Number | |
| 2009-017054-12 | EudraCT Number |
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The sponsor permanently suspended new enrollment into the trial and discontinued the study; which was not related to any concerns over product safety.
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This study will be conducted in two parts. Part 1 will determine whether administration of adavosertib in combination with topotecan and cisplatin is generally well-tolerated and causes clinical objective responses in patients with cervical cancer. Part 1 will also define the recommended Phase 2 dose and maximum tolerated dose (MTD) of the combination of adavosertib with topotecan and cisplatin. Part 2 of the study will evaluate whether treatment with adavosertib in combination with topotecan and cisplatin causes an improvement in progression-free survival (PFS) compared to treatment with topotecan and cisplatin alone and will further evaluate the tolerability of the combination treatment. The primary hypothesis is the combination of adavosertib, topotecan and cisplatin causes objective radiological responses (assessed per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) in ≥30% of participants. Due to the early termination of the study by the sponsor, no participants were enrolled in Part 2 of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: adavosertib + topotecan/cisplatin | Experimental | Part 1: Dose escalation study. adavosertib capsules will be administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3 . Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. |
|
| Part 2: adavosertib + topotecan/cisplatin | Experimental | Part 2: adavosertib capsules will be administered at the dose determined in Part 1 twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. |
|
| Part 2: Placebo to adavosertib + topotecan/cisplatin | Placebo Comparator | Part 2: Placebo to adavosertib capsules will be administered twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| adavosertib | Drug | Adavosertib capsules are administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Percentage of Participants Whose Best Confirmed Response is Partial Response (PR) or Complete Response (CR) | On the basis of Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, PR is at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. CR is the disappearance of all extranodal target lesions, where all pathological lymph nodes must have decreased to <10 mm in the short axis. | Up to approximately 1 year |
| Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | A DLT is a protocol-defined, (hematologic and non-hematologic), AE that must be definitely, probably, or possibly related to the study therapy. A DLT is any of the following: Grade 4-5 hematological toxicity; Grade 3 or Grade 4 neutropenia with fever >38.°C and/or infection requiring antibiotic or anti-fungal treatment. Non-hematologic dose-limiting toxicities are any Grade 3, 4, or 5 non-hematologic toxicity, with specific exceptions. If occurring within the first cycle of combination therapy: unresolved drug-related toxicity, preventing (re) treatment for 3 weeks or more from the date of the next scheduled treatment or any drug-related toxicity preventing the participant from taking at least 75% of the doses of MK-1775 with each administration of chemotherapy. | Up to approximately 1 year |
| Part 2: Length of Time for Progression-free Survival (PFS) | PFS is the length of time during and after treatment that a participant lives, but whose tumor progression does not worsen. PFS is defined as the time from randomization to progressive disease or death, whichever occurs earlier. Tumor volume changes of +20% for progressive disease was used to be consistent with RECIST 1.1. | Up to approximately 1 year |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| Label | URL |
|---|---|
| Merck Clinical Trial Information | View source |
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Due to the early termination of the study by the sponsor, no participants were enrolled in Part 2 of the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: MK-1775 + Topotecan/Cisplatin | Part 1: MK-1775 capsules were administered at 50 mg twice daily on Days 1-4, and once on Day 5 for a total of nine doses per cycle. Each cycle was 21 days. Topotecan was administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3 of each cycle. Cisplatin was administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1 of each cycle. Only a single dose of MK-1775 was administered during Part 1. |
| FG001 | Part 2: MK-1775 + Topotecan/Cisplatin | Part 2: MK-1775 capsules will be administered at the dose determined in Part 1 twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. |
| FG002 | Part 2: Placebo to MK-1775 + Topotecan/Cisplatin | Part 2: Placebo to MK-1775 capsules will be administered twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: MK-1775 + Topotecan/Cisplatin | Part 1: MK-1775 capsules were administered at 50 mg twice daily on Days 1-4, and once on Day 5 for a total of nine doses per cycle. Each cycle was 21 days. Topotecan was administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3 of each cycle. Cisplatin was administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1 of each cycle. Only a single dose of MK-1775 was administered during Part 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part 1: Percentage of Participants Whose Best Confirmed Response is Partial Response (PR) or Complete Response (CR) | On the basis of Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, PR is at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. CR is the disappearance of all extranodal target lesions, where all pathological lymph nodes must have decreased to <10 mm in the short axis. | The study was prematurely terminated, and data were not collected, so no analyses were performed. | Posted | Up to approximately 1 year |
|
At least 30 days following last dose of study therapy or until death (up to approximately 1 year).
All randomized participants who received at least one dose of study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: MK-1775 + Topotecan/Cisplatin | Part 1: MK-1775 capsules were administered at 50 mg twice daily on Days 1-4, and once on Day 5 for a total of nine doses per cycle. Each cycle was 21 days. Topotecan was administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3 of each cycle. Cisplatin was administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1 of each cycle. Only a single dose of MK-1775 was administered during Part 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA Version 14.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C549567 | adavosertib |
| D019772 | Topotecan |
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D017606 | Chlorine Compounds |
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|
| Topotecan | Drug | Topotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. |
|
| Cisplatin | Drug | Cisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. |
|
| Placebo to adavosertib | Drug | Placebo to adavosertib capsules are administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. |
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
| Primary | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | A DLT is a protocol-defined, (hematologic and non-hematologic), AE that must be definitely, probably, or possibly related to the study therapy. A DLT is any of the following: Grade 4-5 hematological toxicity; Grade 3 or Grade 4 neutropenia with fever >38.°C and/or infection requiring antibiotic or anti-fungal treatment. Non-hematologic dose-limiting toxicities are any Grade 3, 4, or 5 non-hematologic toxicity, with specific exceptions. If occurring within the first cycle of combination therapy: unresolved drug-related toxicity, preventing (re) treatment for 3 weeks or more from the date of the next scheduled treatment or any drug-related toxicity preventing the participant from taking at least 75% of the doses of MK-1775 with each administration of chemotherapy. | Participants who completed the first cycle of combination therapy or discontinued from the study due to a DLT attributable to study therapy. One participant who violated the protocol was not assessed for DLTs. | Posted | Number | Number of participants | Up to approximately 1 year |
|
|
|
| Primary | Part 2: Length of Time for Progression-free Survival (PFS) | PFS is the length of time during and after treatment that a participant lives, but whose tumor progression does not worsen. PFS is defined as the time from randomization to progressive disease or death, whichever occurs earlier. Tumor volume changes of +20% for progressive disease was used to be consistent with RECIST 1.1. | Due to the early termination of the study Part 2 was not performed. | Posted | Up to approximately 1 year |
|
|
| 5 |
| 7 |
| 7 |
| 7 |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Escherichia bacteraemia | Infections and infestations | MedDRA Version 14.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
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| Urinary tract obstruction | Renal and urinary disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Tinnitus | Ear and labyrinth disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Discomfort | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Mucosal inflammation | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA Version 14.0 | Systematic Assessment |
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| Device related infection | Infections and infestations | MedDRA Version 14.0 | Systematic Assessment |
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| Hordeolum | Infections and infestations | MedDRA Version 14.0 | Systematic Assessment |
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| Infection | Infections and infestations | MedDRA Version 14.0 | Systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA Version 14.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA Version 14.0 | Systematic Assessment |
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| Skin infection | Infections and infestations | MedDRA Version 14.0 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA Version 14.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
|
| Blood magnesium decreased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
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| Blood sodium decreased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA Version 14.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Hypercreatinaemia | Musculoskeletal and connective tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 14.0 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Neuropathy peripheral | Nervous system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Hydronephrosis | Renal and urinary disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA Version 14.0 | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA Version 14.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA Version 14.0 | Systematic Assessment |
|
| Pelvic venous thrombosis | Vascular disorders | MedDRA Version 14.0 | Systematic Assessment |
|
The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
| D009369 |
| Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D007287 |
| Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |