Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor (RADIANT-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00412061
First received: December 13, 2006
Last updated: August 21, 2014
Last verified: August 2014
Results First Received: October 25, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Carcinoid Tumor
Malignant Carcinoid Syndrome
Interventions: Drug: Octreotide
Drug: Placebo
Drug: Everolimus

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Total 429 patients were randomized to double blind phase of treatment. 170 patients moved to the Open Label Phase.

Reporting Groups
  Description
Octreotide+ Everolimus Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Octreotide+ Placebo Followed by Open Label Arm Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1. Open Label - Patients who had progressive disease in this arm, can move to the open label Everolimus + depot octreotide by choice.

Participant Flow for 2 periods

Period 1:   Double Blind Phase
    Octreotide+ Everolimus     Octreotide+ Placebo Followed by Open Label Arm  
STARTED     216     213  
Safety Set     215 [1]   211 [2]
COMPLETED     0     0  
NOT COMPLETED     216     213  
Disease Progression                 101                 154  
Adverse Event                 61                 16  
Final Primary Analysis                 26                 14  
Withdrawal by Subject                 18                 20  
Death                 6                 3  
Protocol Violation                 3                 4  
New Cander Therapy                 1                 1  
Lost to Follow-up                 0                 1  
[1] 1 patient did not provide at laest one valid post baseline safety assessment.
[2] 1 pt randomized never took drug Another randomized did not have valid post BL safety assessment

Period 2:   Open Label Phase
    Octreotide+ Everolimus     Octreotide+ Placebo Followed by Open Label Arm  
STARTED     0     170  
COMPLETED     0     0  
NOT COMPLETED     0     170  
Disease Progression                 0                 86  
Adverse Event                 0                 46  
Withdrawal by Subject                 0                 15  
Administrative Problems                 0                 13  
Death                 0                 7  
Lost to Follow-up                 0                 2  
New Cancer Therapy                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Octreotide+ Everolimus Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Octreotide+ Placebo Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
Total Total of all reporting groups

Baseline Measures
    Octreotide+ Everolimus     Octreotide+ Placebo     Total  
Number of Participants  
[units: participants]
  216     213     429  
Age  
[units: years]
Mean ± Standard Deviation
  60.1  ± 10.72     59.4  ± 11.13     59.8  ± 10.92  
Gender  
[units: Participants]
     
Female     119     89     208  
Male     97     124     221  



  Outcome Measures
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1.  Primary:   Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review   [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010 ]

2.  Secondary:   Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)   [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010 ]

3.  Secondary:   Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline 5-hydroxyindoleacetic Acid (5-HIAA) Level   [ Time Frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010 ]

4.  Secondary:   Overall Survival Using Kaplan-Meier Methodology   [ Time Frame: Months 12, 24, 36, 48 ]

5.  Secondary:   Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Double-Blind Phase)   [ Time Frame: From first day of treatment up to 28 days after last day of treatment in double blind ]

6.  Secondary:   Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Open Label Phase)   [ Time Frame: From first day of treatment up to 28 days after last day of treatment in double blind ]

7.  Secondary:   Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline Chromogranin A (CgA)   [ Time Frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010 ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description Double blind period, Safety Set consists all patients received at least one dose of study drug and who had at least one valid post-baseline safety assessment. The Open-label Set consists all patients received at least one dose of open-label everolimus and who had at least one valid safety assessment after initiation of open-label treatment

Reporting Groups
  Description
Everolimus + Octreotide Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Placebo + Octreotide Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
Everolimus Open Label Open Label - Patients who had progressive disease in this arm, can move to the open label Everolimus + depot octreotide by choice.

Serious Adverse Events
    Everolimus + Octreotide     Placebo + Octreotide     Everolimus Open Label  
Total, serious adverse events        
# participants affected / at risk     126/215 (58.60%)     74/211 (35.07%)     93/170 (54.71%)  
Blood and lymphatic system disorders        
Anaemia † 1      
# participants affected / at risk     4/215 (1.86%)     2/211 (0.95%)     4/170 (2.35%)  
Disseminated intravascular coagulation † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Febrile neutropenia † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Haemorrhagic anaemia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     2/170 (1.18%)  
Leukopenia † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Pancytopenia † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Thrombocytopenia † 1      
# participants affected / at risk     3/215 (1.40%)     0/211 (0.00%)     1/170 (0.59%)  
Cardiac disorders        
Acute myocardial infarction † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Angina pectoris † 1      
# participants affected / at risk     2/215 (0.93%)     3/211 (1.42%)     1/170 (0.59%)  
Aortic valve incompetence † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Arrhythmia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Atrial fibrillation † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Atrial flutter † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Carcinoid heart disease † 1      
# participants affected / at risk     2/215 (0.93%)     2/211 (0.95%)     2/170 (1.18%)  
Cardiac arrest † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Cardiac failure † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     0/170 (0.00%)  
Cardiac failure congestive † 1      
# participants affected / at risk     2/215 (0.93%)     2/211 (0.95%)     0/170 (0.00%)  
Cardiac valve disease † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Cardio-respiratory arrest † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     0/170 (0.00%)  
Cardiopulmonary failure † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Coronary artery disease † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Coronary artery occlusion † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Dilatation ventricular † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Left ventricular dysfunction † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Mitral valve stenosis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Myocardial infarction † 1      
# participants affected / at risk     1/215 (0.47%)     2/211 (0.95%)     1/170 (0.59%)  
Myocardial ischaemia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Palpitations † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Pericardial effusion † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Pulmonary valve incompetence † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Pulmonary valve stenosis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Right ventricular failure † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Stress cardiomyopathy † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Tachycardia paroxysmal † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Tricuspid valve disease † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Tricuspid valve incompetence † 1      
# participants affected / at risk     1/215 (0.47%)     2/211 (0.95%)     0/170 (0.00%)  
Tricuspid valve prolapse † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Tricuspid valve stenosis † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Congenital, familial and genetic disorders        
Atrial septal defect † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     0/170 (0.00%)  
Ear and labyrinth disorders        
Vertigo † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Endocrine disorders        
Adrenocortical insufficiency acute † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Carcinoid crisis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Carcinoid syndrome † 1      
# participants affected / at risk     2/215 (0.93%)     1/211 (0.47%)     2/170 (1.18%)  
Eye disorders        
Diplopia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Gastrointestinal disorders        
Abdominal adhesions † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Abdominal distension † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Abdominal hernia † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     1/170 (0.59%)  
Abdominal pain † 1      
# participants affected / at risk     15/215 (6.98%)     11/211 (5.21%)     11/170 (6.47%)  
Abdominal pain lower † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     0/170 (0.00%)  
Abdominal pain upper † 1      
# participants affected / at risk     1/215 (0.47%)     2/211 (0.95%)     1/170 (0.59%)  
Ascites † 1      
# participants affected / at risk     0/215 (0.00%)     5/211 (2.37%)     0/170 (0.00%)  
Colitis † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     1/170 (0.59%)  
Constipation † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Diarrhoea † 1      
# participants affected / at risk     9/215 (4.19%)     5/211 (2.37%)     7/170 (4.12%)  
Duodenal obstruction † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Duodenal stenosis † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     2/170 (1.18%)  
Enteritis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Faeces discoloured † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Food poisoning † 1      
# participants affected / at risk     0/215 (0.00%)     2/211 (0.95%)     0/170 (0.00%)  
Gastric haemorrhage † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Gastric ulcer † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Gastritis erosive † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Gastrointestinal angiodysplasia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Gastrointestinal fistula † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Gastrointestinal haemorrhage † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     2/170 (1.18%)  
Gastrooesophageal reflux disease † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Haematemesis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Haematochezia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Haemorrhoids † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     0/170 (0.00%)  
Ileus † 1      
# participants affected / at risk     5/215 (2.33%)     1/211 (0.47%)     0/170 (0.00%)  
Inguinal hernia, obstructive † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Intestinal angina † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Intestinal obstruction † 1      
# participants affected / at risk     2/215 (0.93%)     5/211 (2.37%)     3/170 (1.76%)  
Intestinal perforation † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     2/170 (1.18%)  
Lip oedema † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Lower gastrointestinal haemorrhage † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Melaena † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Nausea † 1      
# participants affected / at risk     4/215 (1.86%)     4/211 (1.90%)     2/170 (1.18%)  
Oesophageal spasm † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Pancreatitis acute † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Pneumatosis intestinalis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Rectal haemorrhage † 1      
# participants affected / at risk     3/215 (1.40%)     0/211 (0.00%)     1/170 (0.59%)  
Retroperitoneal haematoma † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Small intestinal haemorrhage † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Small intestinal obstruction † 1      
# participants affected / at risk     8/215 (3.72%)     3/211 (1.42%)     4/170 (2.35%)  
Small intestinal stenosis † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     0/170 (0.00%)  
Stomatitis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Subileus † 1      
# participants affected / at risk     3/215 (1.40%)     2/211 (0.95%)     0/170 (0.00%)  
Upper gastrointestinal haemorrhage † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Vomiting † 1      
# participants affected / at risk     7/215 (3.26%)     6/211 (2.84%)     5/170 (2.94%)  
General disorders        
Asthenia † 1      
# participants affected / at risk     2/215 (0.93%)     3/211 (1.42%)     1/170 (0.59%)  
Brain death † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Chest pain † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     1/170 (0.59%)  
Chills † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Face oedema † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Fatigue † 1      
# participants affected / at risk     2/215 (0.93%)     1/211 (0.47%)     0/170 (0.00%)  
General physical health deterioration † 1      
# participants affected / at risk     6/215 (2.79%)     3/211 (1.42%)     5/170 (2.94%)  
Generalised oedema † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Hypothermia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Malaise † 1      
# participants affected / at risk     2/215 (0.93%)     1/211 (0.47%)     0/170 (0.00%)  
Non-cardiac chest pain † 1      
# participants affected / at risk     3/215 (1.40%)     0/211 (0.00%)     0/170 (0.00%)  
Oedema peripheral † 1      
# participants affected / at risk     3/215 (1.40%)     4/211 (1.90%)     3/170 (1.76%)  
Pain † 1      
# participants affected / at risk     1/215 (0.47%)     2/211 (0.95%)     0/170 (0.00%)  
Performance status decreased † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Pyrexia † 1      
# participants affected / at risk     8/215 (3.72%)     3/211 (1.42%)     3/170 (1.76%)  
Spinal pain † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Sudden death † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Hepatobiliary disorders        
Bile duct obstruction † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Cholangitis † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Cholangitis acute † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Cholecystitis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Cholecystitis acute † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     1/170 (0.59%)  
Cholelithiasis † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Cholestasis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Hepatic failure † 1      
# participants affected / at risk     2/215 (0.93%)     1/211 (0.47%)     0/170 (0.00%)  
Hepatic function abnormal † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     0/170 (0.00%)  
Hepatocellular injury † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Hepatotoxicity † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Hyperbilirubinaemia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Jaundice † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Immune system disorders        
Drug hypersensitivity † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Infections and infestations        
Abdominal wall abscess † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Abscess intestinal † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Arthritis infective † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Aspergillosis † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Bacteraemia † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     0/170 (0.00%)  
Bronchiolitis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Bronchopneumonia † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Cellulitis † 1      
# participants affected / at risk     3/215 (1.40%)     0/211 (0.00%)     0/170 (0.00%)  
Cholecystitis infective † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Clostridium difficile colitis † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Diverticulitis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Erysipelas † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Escherichia sepsis † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Gastroenteritis † 1      
# participants affected / at risk     2/215 (0.93%)     1/211 (0.47%)     2/170 (1.18%)  
Gastroenteritis viral † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Herpes zoster † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Infected skin ulcer † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Infection † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Influenza † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Localised infection † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     2/170 (1.18%)  
Lung infection † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     2/170 (1.18%)  
Osteomyelitis † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Peritonitis † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Pneumonia † 1      
# participants affected / at risk     9/215 (4.19%)     1/211 (0.47%)     5/170 (2.94%)  
Pneumonia viral † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Sepsis † 1      
# participants affected / at risk     2/215 (0.93%)     1/211 (0.47%)     4/170 (2.35%)  
Sinusitis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Staphylococcal infection † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Urinary tract infection † 1      
# participants affected / at risk     2/215 (0.93%)     2/211 (0.95%)     0/170 (0.00%)  
Urinary tract infection bacterial † 1      
# participants affected / at risk     0/215 (0.00%)     2/211 (0.95%)     0/170 (0.00%)  
Urosepsis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Injury, poisoning and procedural complications        
Bone fissure † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Femoral neck fracture † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     0/170 (0.00%)  
Fractured sacrum † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Heat exhaustion † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Hip fracture † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Humerus fracture † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Joint injury † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Post procedural complication † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Post procedural haemorrhage † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Pulmonary contusion † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Rib fracture † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Scapula fracture † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Seroma † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Toxicity to various agents † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Traumatic intracranial haemorrhage † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Investigations        
Alanine aminotransferase increased † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Aspartate aminotransferase increased † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     1/170 (0.59%)  
Blood alkaline phosphatase increased † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Blood creatinine increased † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     4/170 (2.35%)  
Blood urea increased † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Cardiac murmur † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Coagulation time shortened † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Heart rate increased † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Lipase increased † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Weight decreased † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     0/170 (0.00%)  
Metabolism and nutrition disorders        
Cachexia † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     0/170 (0.00%)  
Decreased appetite † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     2/170 (1.18%)  
Dehydration † 1      
# participants affected / at risk     7/215 (3.26%)     1/211 (0.47%)     3/170 (1.76%)  
Failure to thrive † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Hypercalcaemia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Hyperglycaemia † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     3/170 (1.76%)  
Hypocalcaemia † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     1/170 (0.59%)  
Hypoglycaemia † 1      
# participants affected / at risk     2/215 (0.93%)     1/211 (0.47%)     0/170 (0.00%)  
Hypokalaemia † 1      
# participants affected / at risk     4/215 (1.86%)     0/211 (0.00%)     1/170 (0.59%)  
Hypomagnesaemia † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     0/170 (0.00%)  
Hypophosphataemia † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Malnutrition † 1      
# participants affected / at risk     1/215 (0.47%)     2/211 (0.95%)     0/170 (0.00%)  
Metabolic acidosis † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     1/170 (0.59%)  
Type 2 diabetes mellitus † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Musculoskeletal and connective tissue disorders        
Arthralgia † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Arthritis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Back pain † 1      
# participants affected / at risk     0/215 (0.00%)     4/211 (1.90%)     1/170 (0.59%)  
Bone pain † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     0/170 (0.00%)  
Flank pain † 1      
# participants affected / at risk     2/215 (0.93%)     1/211 (0.47%)     0/170 (0.00%)  
Muscle spasms † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Musculoskeletal chest pain † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Neck pain † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Osteoarthritis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Osteoporosis † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Pain in extremity † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     0/170 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)        
B-cell type acute leukaemia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Brain neoplasm malignant † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Cancer pain † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Glioblastoma † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Lung infiltration malignant † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Malignant pleural effusion † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Metastatic pain † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Pancreatic carcinoma † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Tumour compression † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Nervous system disorders        
Cerebral ischaemia † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Cerebrovascular accident † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Convulsion † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Depressed level of consciousness † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Dizziness postural † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Encephalopathy † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Facial paresis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Grand mal convulsion † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Headache † 1      
# participants affected / at risk     0/215 (0.00%)     2/211 (0.95%)     0/170 (0.00%)  
Hypoaesthesia † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Intracranial haematoma † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Lethargy † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     0/170 (0.00%)  
Mental impairment † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Metabolic encephalopathy † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Radicular syndrome † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Radiculopathy † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Sciatica † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     0/170 (0.00%)  
Subarachnoid haemorrhage † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Syncope † 1      
# participants affected / at risk     2/215 (0.93%)     1/211 (0.47%)     2/170 (1.18%)  
Psychiatric disorders        
Confusional state † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     1/170 (0.59%)  
Depression † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Hallucination † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Mental status changes † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Renal and urinary disorders        
Bladder tamponade † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Calculus ureteric † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Calculus urinary † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Eosinophilic cystitis † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Haematuria † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     1/170 (0.59%)  
Hydronephrosis † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Nephrolithiasis † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     2/170 (1.18%)  
Renal failure † 1      
# participants affected / at risk     4/215 (1.86%)     0/211 (0.00%)     3/170 (1.76%)  
Renal failure acute † 1      
# participants affected / at risk     3/215 (1.40%)     1/211 (0.47%)     1/170 (0.59%)  
Renal failure chronic † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Renal impairment † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Renal infarct † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Ureteric obstruction † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Urinary bladder haemorrhage † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Urinary retention † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Reproductive system and breast disorders        
Testicular swelling † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Respiratory, thoracic and mediastinal disorders        
Acute respiratory failure † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Atelectasis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Cough † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Dyspnoea † 1      
# participants affected / at risk     8/215 (3.72%)     2/211 (0.95%)     1/170 (0.59%)  
Granulomatous pneumonitis † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Haemoptysis † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Hypoxia † 1      
# participants affected / at risk     3/215 (1.40%)     1/211 (0.47%)     0/170 (0.00%)  
Interstitial lung disease † 1      
# participants affected / at risk     3/215 (1.40%)     0/211 (0.00%)     1/170 (0.59%)  
Laryngeal oedema † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Lung infiltration † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Organising pneumonia † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Pleural effusion † 1      
# participants affected / at risk     3/215 (1.40%)     0/211 (0.00%)     2/170 (1.18%)  
Pneumonitis † 1      
# participants affected / at risk     2/215 (0.93%)     0/211 (0.00%)     2/170 (1.18%)  
Pneumothorax † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Pulmonary embolism † 1      
# participants affected / at risk     6/215 (2.79%)     1/211 (0.47%)     3/170 (1.76%)  
Pulmonary hypertension † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Respiratory arrest † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Respiratory distress † 1      
# participants affected / at risk     0/215 (0.00%)     0/211 (0.00%)     1/170 (0.59%)  
Respiratory failure † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     0/170 (0.00%)  
Tachypnoea † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Skin and subcutaneous tissue disorders        
Angioedema † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     1/170 (0.59%)  
Palmar-plantar erythrodysaesthesia syndrome † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Vascular disorders        
Aortic dissection † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Deep vein thrombosis † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     2/170 (1.18%)  
Flushing † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Haematoma † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Hypertension † 1      
# participants affected / at risk     1/215 (0.47%)     1/211 (0.47%)     1/170 (0.59%)  
Hypotension † 1      
# participants affected / at risk     0/215 (0.00%)     1/211 (0.47%)     0/170 (0.00%)  
Jugular vein thrombosis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Orthostatic hypotension † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Phlebitis † 1      
# participants affected / at risk     1/215 (0.47%)     0/211 (0.00%)     0/170 (0.00%)  
Events were collected by systematic assessment
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


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Publications automatically indexed to this study:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00412061     History of Changes
Other Study ID Numbers: CRAD001C2325, 2006-004507-18
Study First Received: December 13, 2006
Results First Received: October 25, 2011
Last Updated: August 21, 2014
Health Authority: United States: Food and Drug Administration