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| ID | Type | Description | Link |
|---|---|---|---|
| MK-0683-088 | Other Identifier | Merck Protocol Number | |
| 2008-003752-30 | EudraCT Number |
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Study of the efficacy and safety of bortezomib administered in combination with vorinostat in patients with relapsed or refractory multiple myeloma. Histone deacetylases (HDAC) facilitate gene transcription by modulating the uncoiling of chromatin. HDAC function is dysregulated in hematologic and solid malignancies, and this dysregulation may result in over-expression of oncogenes. Thus, inhibition of HDACs may result in anti-cancer effects. HDAC inhibitors, like vorinostat, represent a new class of antitumor agents that have the ability to induce antiproliferative effects including cyto-differentiation, cell cycle growth arrest or apoptosis in various cancer cell lines. Several studies have investigated the in vitro antimyeloma activity of vorinostat in combination with bortezomib and have demonstrated that vorinostat may act synergistically with bortezomib to modulate tumor cell growth. Mitsiades et al have shown that vorinostat enhances the sensitivity of bortezomib. Pei et al found that exposure of human multiple myeloma cell lines & patient-derived multiple myeloma cells to bortezomib and vorinostat resulted in synergistic interactions as a result of: (1) Interruption of NF-kB & related signaling pathways (JNK, XIAP, Mcl-1, etc.) (2) Inhibition of Hsp90 (3)Induction of ER stress signal and (4) acetylation of Dynein/disruption of aggresome function/formation, salvage for ubiquitinated proteins. In addition a marked increase in mitochondrial injury, caspase activation, and apoptosis was also observed. Bortezomib is indicated for the treatment of patients with multiple myeloma. Two Phase I dose-ranging studies of a regimen combining vorinostat and bortezomib among patients with relapsed as well asend-stage, refractory multiple myeloma have been conducted. These studies enrolled a total of 57 patients. In these studies, administration of vorinostat with standard doses of bortezomib resulted in responses in 20/45 (44%) evaluable patients (Weber et al 2007, Badros et al 2007). The purpose of the present study is to definitively evaluate the clinical activity of vorinostat in combination with bortezomib inpatients with multiple myeloma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vorinostat + Bortezomib | Experimental | Participants will receive vorinostat four 100 mg capsules (400 mg total) orally 0-30 minutes after a meal on Days 1-14 of a 21-day treatment cycle and bortezomib 1.3 mg/m^2 by intravenous injection on Days 1, 4, 8, and 11 of a 21-day treatment cycle. |
|
| Placebo + Bortezomib | Placebo Comparator | Participants will receive four placebo capsules orally 0-30 minutes after a meal on Days 1-14 of a 21-day treatment cycle and bortezomib 1.3 mg/m^2 by intravenous injection on Days 1, 4, 8, and 11 of a 21-day treatment cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vorinostat | Drug | Four 100 mg capsules vorinostat taken orally, once daily, on Days 1 through 14 of each 21-day treatment cycle. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) | Progression-free survival was measured from the start of the treatment to the time when the criteria for progression was met or death due to any cause (whichever is first recorded). Response to study therapy was assessed using European Blood and Marrow Transplantation Group (EBMT) Criteria. A stratified Cox proportional hazards model was used with Efron's likelihood approximation to account for ties in event times. | From randomization to event of disease progression or death assessed up to 32 months (final study analysis) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Grade 3-5 Clinical or Laboratory Adverse Events (AEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. Grades come from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Per protocol, clinical and laboratory AEs are presented as a combined total for each grade. |
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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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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24055414 | Result | Dimopoulos M, Siegel DS, Lonial S, Qi J, Hajek R, Facon T, Rosinol L, Williams C, Blacklock H, Goldschmidt H, Hungria V, Spencer A, Palumbo A, Graef T, Eid JE, Houp J, Sun L, Vuocolo S, Anderson KC. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol. 2013 Oct;14(11):1129-1140. doi: 10.1016/S1470-2045(13)70398-X. Epub 2013 Sep 19. |
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637 participants were randomized to treatment and 635 participants received at least 1 dose of MK-0683 or placebo: 315 participants were treated with vorinostat + bortezomib and 320 participants were treated with placebo + bortezomib.
This study enrolled participants with an established diagnosis of multiple myeloma based on standard criteria that have received at least 1 but not more than 3 prior anti-myeloma regimens and have demonstrated progressive disease after the most recent treatment regimen. Additional inclusion and exclusion criteria applied.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vorinostat + Bortezomib | Participants will receive vorinostat four 100 mg capsules (400 mg total) orally 0-30 minutes after a meal on Days 1 through 14 of a 21-day treatment cycle and bortezomib 1.3 mg/m^2 by intravenous injection on Days 1, 4, 8, and 11 of a 21-day treatment cycle. |
| FG001 | Placebo + Bortezomib | Participants will receive four placebo capsules orally 0-30 minutes after a meal on Days 1 through 14 of a 21-day treatment cycle and bortezomib 1.3 mg/m^2 by intravenous injection on Days 1, 4, 8, and 11 of a 21-day treatment cycle. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Vorinostat + Bortezomib | Participants will receive vorinostat four 100 mg capsules (400 mg total) orally 0-30 minutes after a meal on Days 1 through 14 of a 21-day treatment cycle and bortezomib 1.3 mg/m^2 by intravenous injection on Days 1, 4, 8, and 11 of a 21-day treatment cycle. |
| BG001 |
| 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 | Progression-Free Survival (PFS) | Progression-free survival was measured from the start of the treatment to the time when the criteria for progression was met or death due to any cause (whichever is first recorded). Response to study therapy was assessed using European Blood and Marrow Transplantation Group (EBMT) Criteria. A stratified Cox proportional hazards model was used with Efron's likelihood approximation to account for ties in event times. | The analysis population includes all randomized participants. | Posted | Median | 95% Confidence Interval | Months | From randomization to event of disease progression or death assessed up to 32 months (final study analysis) |
|
Up to 722 days.
Adverse events were reported for the All Participants as Treated Population that included 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 | Vorinostat + Bortezomib | Participants will receive vorinostat four 100 mg capsules (400 mg total) orally 0-30 minutes after a meal on Days 1 through 14 of a 21-day treatment cycle and bortezomib 1.3 mg/m^2 by intravenous injection on Days 1, 4, 8, and 11 of a 21-day treatment cycle. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 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 |
|---|---|
| D009101 | Multiple Myeloma |
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| ID | Term |
|---|---|
| D006425 | Hemic and Lymphatic Diseases |
| D008206 | Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077337 | Vorinostat |
| D000069286 | Bortezomib |
| ID | Term |
|---|---|
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
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| bortezomib | Drug | 1.3 mg/m2 of bortezomib by IV push, on Days 1, 4, 8, and 11 of each 21-day treatment cycle. |
|
|
| placebo to vorinostat | Drug | Four placebo capsules taken orally, once daily, on Days 1 through 14 of each 21-day treatment cycle. |
|
| Up to 722 days |
| Overall Survival | Overall survival was measured from the start of the treatment to death due to any cause. Overall Survival is represented as the number of deaths per 100-person- months and was computed by dividing the number of participants with an event of death that occurred during the study follow-up period by the total duration of follow-up (in 100 months) for all the participants in each cohort since participants had different lengths of follow-up. | From randomization up to 32 months (final study analysis) |
| Time to Progression | Time to progression was measured from the start of the treatment to the time when the criteria for progression was met or death due to myeloma (whichever is first recorded). Response to study therapy was assessed using European Blood and Marrow Transplantation Group (EBMT) Criteria. A stratified Cox proportional hazards model was used with Efron's likelihood approximation to account for ties in event times. | Baseline and at the end of each 21-day Cycle assessed up to 32 months (final study analysis) |
| Objective Response Rate | Objective response rate was measured as the proportion of patients who achieved a confirmed partial response or better during the course of the study. Response to study therapy was assessed using EBMT Criteria and confirmed by Independent Adjudication Review. | Baseline and at the end of each 21-day Cycle assessed up to 32 months (final study analysis) |
| Lost to Follow-up |
|
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Adverse Event |
|
| Death |
|
| Not Treated |
|
| Placebo + Bortezomib |
Participants will receive four placebo capsules orally 0-30 minutes after a meal on Days 1 through 14 of a 21-day treatment cycle and bortezomib 1.3 mg/m^2 by intravenous injection on Days 1, 4, 8, and 11 of a 21-day treatment cycle. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Placebo + Bortezomib | Participants will receive four placebo capsules orally 0-30 minutes after a meal on Days 1 through 14 of a 21-day treatment cycle and bortezomib 1.3 mg/m^2 by intravenous injection on Days 1, 4, 8, and 11 of a 21-day treatment cycle. |
|
|
|
| Secondary | Number of Participants With Grade 3-5 Clinical or Laboratory Adverse Events (AEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. Grades come from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Per protocol, clinical and laboratory AEs are presented as a combined total for each grade. | The analysis population includes all randomized participants who received ≥1 dose of study medication. | Posted | Count of Participants | Participants | Up to 722 days |
|
|
|
| Secondary | Overall Survival | Overall survival was measured from the start of the treatment to death due to any cause. Overall Survival is represented as the number of deaths per 100-person- months and was computed by dividing the number of participants with an event of death that occurred during the study follow-up period by the total duration of follow-up (in 100 months) for all the participants in each cohort since participants had different lengths of follow-up. | The analysis population includes all randomized participants. | Posted | Number | 95% Confidence Interval | Events/100-person Months | From randomization up to 32 months (final study analysis) |
|
|
|
|
| Secondary | Time to Progression | Time to progression was measured from the start of the treatment to the time when the criteria for progression was met or death due to myeloma (whichever is first recorded). Response to study therapy was assessed using European Blood and Marrow Transplantation Group (EBMT) Criteria. A stratified Cox proportional hazards model was used with Efron's likelihood approximation to account for ties in event times. | The analysis population includes all randomized participants. | Posted | Median | 95% Confidence Interval | Months | Baseline and at the end of each 21-day Cycle assessed up to 32 months (final study analysis) |
|
|
|
| Secondary | Objective Response Rate | Objective response rate was measured as the proportion of patients who achieved a confirmed partial response or better during the course of the study. Response to study therapy was assessed using EBMT Criteria and confirmed by Independent Adjudication Review. | The analysis population includes all randomized participants who received ≥1 dose of study medication. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Baseline and at the end of each 21-day Cycle assessed up to 32 months (final study analysis) |
|
|
|
| 130 |
| 315 |
| 312 |
| 315 |
| EG001 | Placebo + Bortezomib | Participants will receive four placebo capsules orally 0-30 minutes after a meal on Days 1 through 14 of a 21-day treatment cycle and bortezomib 1.3 mg/m^2 by intravenous injection on Days 1, 4, 8, and 11 of a 21-day treatment cycle. | 138 | 320 | 306 | 320 |
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haemolysis | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Acute myocardial infarction | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Arrhythmia | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cardiac failure congestive | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cardiopulmonary failure | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperparathyroidism primary | Endocrine disorders | MedDRA 14.0 | Systematic Assessment |
|
| Retinal detachment | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Ileus paralytic | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Odynophagia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pancreatitis acute | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pneumatosis intestinalis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Death | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Multi-organ failure | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pelvic mass | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Swelling | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hepatic necrosis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Bronchitis pneumococcal | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Clostridial infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Conjunctivitis bacterial | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Device related sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Escherichia sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Fungal infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Gastroenteritis salmonella | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Gastrointestinal viral infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| H1N1 influenza | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Haemophilus infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Hepatitis B | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Herpes simplex | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Herpes zoster ophthalmic | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Lobar pneumonia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Pneumococcal sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Respiratory tract infection viral | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Tracheobronchitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Tuberculosis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Upper respiratory tract infection bacterial | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Metabolic disorder | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Spondylitis | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Brain oedema | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cerebral ischaemia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diabetic coma | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Paraplegia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Spinal cord compression | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Anxiety disorder | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Completed suicide | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Azotaemia | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bronchitis chronic | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Circulatory collapse | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Shock | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
An investigator may not independently publish the results for their study site until after the multicenter publication, or 24 months after completion of study.
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. Sponsor review can be expedited to meet publication guidelines.
| D000588 |
| Amines |
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Grade 5 |
|