A Study to Evaluate Safety and Efficacy of Panobinostat in Participants With Primary Myelofibrosis
Study Details
Study Description
Brief Summary
This study assessed the safety and efficacy of Panobinostat as a single agent in the treatment of Primary Myelofibrosis, Post-Polycythemia Vera and Post-Essential Thrombocythemia. There were two cohorts - participants with JAK2 mutation and participants without JAK2 mutation.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Panobinostat Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible. |
Drug: Panobinostat
Panobinostat oral capsules
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response (OR) Rate Per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria [Up to approximately 2 years]
Overall response (OR) = Complete remission (CR) + Partial remission (PR) + Clinical improvement (CI). CR: complete resolution of disease-related symptoms and signs with hemoglobin level 110 grams per deciliter (g/L), platelet count 100 x 10^9/liter (L), and absolute neutrophil count (ANC) 1.0 x 10^9/L, all 3 blood counts < upper normal limit (UNL), normal leukocyte differential, and bone marrow histologic remission. PR= all of the criteria for CR except the requirement for bone marrow histologic remission. CI= minimum 20 g/L increase in hemoglobin for transfusion or becoming transfusion independent or reduction in splenomegaly ≥ 50% or 100% increase in platelet count and absolute platelet count of 50 x 10^9/L and 100% increase in ANC of at least 0.5 x 10^9/L.
Secondary Outcome Measures
- Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 [Baseline, Cycle 6 (each cycle was of 28 days)]
The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement.
- Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores [Baseline, Cycles 2, and 4 (each cycle was of 28-days)]
The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement.
- Number of Participants With Adverse Events (AEs), and Serious Adverse Events (SAEs) [AE: From the start of treatment up to 28 days after last study dose (up to approximately 2 years); SAE: From time of informed consent up to 4 weeks after last study dose (approximately 2 years)]
An adverse event is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. SAEs was an undesirable sign, symptom or medical condition which is: life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, requires hospitalizations or prolongation of hospitalizations, or is medically significant
Other Outcome Measures
- Monthly Capsule Counts to Assess Compliance to Panobinostat Treatment [Up to approximately 2 years]
- To Compare the Response to Panobinostat in Patients With the JAK2 V617F Mutation to Those Without the JAK2 V617F Mutation [Up to approximately 2 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Diagnosis of myelofibrosis, either primary myelofibrosis (PMF), post- polycythemia vera (PV) or post-essential thrombocythemia (ET) myelofibrosis (MF) with international prognostic scoring system (IPSS) score of 2 (intermediate risk) or 3 (high risk) plus at least one of the following:
Symptomatic spenomegaly (≥10 centimeter [cm] below costal margin [BCM]) Hemoglobin < 10 or red cell transfusion dependent. (The presence of a janus kinase (JAK2) V617F mutation is not required for study entry).
- Participants must meet the following laboratory criteria:
-
Participants can be either JAK2 V617F mutated or wild type.
-
Serum potassium, magnesium, phosphorous, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution Note: Potassium, magnesium, phosphorous, sodium, and/or calcium supplements maybe given to correct values that are < lower limit of normal (LLN). Post correction values must not be deemed to be a clinically significant abnormality prior to participants being dosed.
-
Creatinine < 1.5 X upper limit of normal (ULN) or calculated creatinine clearance (CrCl) ≥ 50 milliliter per minute (mL/min) (modification of diet in renal diseases [MDRD] formula).
-
Aspartate aminotransferase [AST] and alanine transaminase [ALT] ≤ 2.5 x ULN.
-
Serum total bilirubin ≤ 1.5 x ULN.
-
Eastern cooperative oncology group (ECOG) performance status of ≤ 2.
-
Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
Exclusion Criteria:
-
Prior histone deacetylases (HDAC), deacetylase (DAC), heat shock protein 90 (HSP90) inhibitors or valproic acid for the treatment of cancer.
-
Previous treatment with JAK2 inhibitors.
-
Any participant who has previously received radiation therapy to ≥ 30% of the bone marrow.
-
Impaired cardiac function or clinically significant cardiac diseases.
-
Participant with unresolved diarrhoea ≥ grade 2.
-
Participants using medications that have a relative risk of prolonging the QT interval or inducing Torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug.
-
Participants who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of surgery.
-
Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test at screening and at baseline.
-
Male participants whose sexual partners are WOCBP not using effective birth control.
-
Participants with a prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix).
-
Participants with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required.
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Mayo Clinic - Scottsdale | Scottsdale | Arizona | United States | 85259 |
2 | City of Hope National Medical Center | Duarte | California | United States | 91010 |
3 | Stanford Comprehensive Cancer Center | Stanford | California | United States | 94305 |
4 | Medical College of Georgia | Augusta | Georgia | United States | 30912 |
5 | Northwestern University Feinberg School of Medicine | Chicago | Illinois | United States | 60611 |
6 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
7 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
8 | Mayo Clinic - Rochester | Rochester | Minnesota | United States | 55905 |
9 | New York Presbyterian Hospital - Weill Cornell Medical College | New York | New York | United States | 10021 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CLBH589BUS58
Study Results
Participant Flow
Recruitment Details | Participants were enrolled at 9 investigative centers in the United States from 31 August 2009 to 29 August 2011. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Panobinostat |
---|---|
Arm/Group Description | Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible. |
Period Title: Overall Study | |
STARTED | 35 |
COMPLETED | 0 |
NOT COMPLETED | 35 |
Baseline Characteristics
Arm/Group Title | Panobinostat |
---|---|
Arm/Group Description | Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible. |
Overall Participants | 35 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
68.3
(10.30)
|
Sex: Female, Male (Count of Participants) | |
Female |
10
28.6%
|
Male |
25
71.4%
|
Outcome Measures
Title | Overall Response (OR) Rate Per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria |
---|---|
Description | Overall response (OR) = Complete remission (CR) + Partial remission (PR) + Clinical improvement (CI). CR: complete resolution of disease-related symptoms and signs with hemoglobin level 110 grams per deciliter (g/L), platelet count 100 x 10^9/liter (L), and absolute neutrophil count (ANC) 1.0 x 10^9/L, all 3 blood counts < upper normal limit (UNL), normal leukocyte differential, and bone marrow histologic remission. PR= all of the criteria for CR except the requirement for bone marrow histologic remission. CI= minimum 20 g/L increase in hemoglobin for transfusion or becoming transfusion independent or reduction in splenomegaly ≥ 50% or 100% increase in platelet count and absolute platelet count of 50 x 10^9/L and 100% increase in ANC of at least 0.5 x 10^9/L. |
Time Frame | Up to approximately 2 years |
Outcome Measure Data
Analysis Population Description |
---|
FAS population included all participants who received at least one dose of study drug. |
Arm/Group Title | Panobinostat |
---|---|
Arm/Group Description | Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible. |
Measure Participants | 35 |
Number (95% Confidence Interval) [percentage of participants] |
2.9
8.3%
|
Title | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 |
---|---|
Description | The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement. |
Time Frame | Baseline, Cycle 6 (each cycle was of 28 days) |
Outcome Measure Data
Analysis Population Description |
---|
FAS population included all participants who received at least one dose of study drug. All 35 participants were evaluated for this Outcome. The Number Analyzed represented in each row differs from the Overall Number of Participants Analyzed as scores that are presented are for the participants who reported the measured event at the time evaluated. |
Arm/Group Title | Panobinostat |
---|---|
Arm/Group Description | Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible. |
Measure Participants | 35 |
Cycle 6, Day 1: Fatigue Right now |
-1.5
(2.12)
|
Cycle 6, Day 1: Fatigue Usual Past 24 Hours |
-1.0
(5.66)
|
Cycle 6, Day 1: Fatigue Worst Past 24 Hours |
-3.0
(2.83)
|
Cycle 6, Day 1: General Activity |
-3.5
(2.12)
|
Cycle 6, Day 1: Mood |
-3.5
(3.54)
|
Cycle 6, Day 1: Walking Ability |
-3.0
(5.66)
|
Cycle 6, Day 1: Normal Work |
-4.0
(4.24)
|
Cycle 6, Day 1: Relations with Other People |
-4.5
(2.12)
|
Cycle 6, Day 1: Enjoyment of Life |
-5.0
(4.24)
|
Cycle 6, Day 1: Filling up quickly when you eat |
1.0
(1.41)
|
Cycle 6, Day 1: Abdominal pain or Discomfort |
0.5
(2.12)
|
Cycle 6, Day 1: Inactivity |
-0.5
(3.54)
|
Cycle 6, Day 1: Cough |
-1.5
(2.12)
|
Cycle 6, Day 1: Night Sweats |
-0.5
(0.71)
|
Cycle 6, Day 1: Itching |
1.5
(2.12)
|
Cycle 6, Day 1: Bone Pain |
-2.5
(0.71)
|
Cycle 6, Day 1: What is Overall Quality of Life? |
-2.5
(2.12)
|
Title | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores |
---|---|
Description | The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement. |
Time Frame | Baseline, Cycles 2, and 4 (each cycle was of 28-days) |
Outcome Measure Data
Analysis Population Description |
---|
FAS population included all participants who received at least one dose of study drug. All 35 participants were evaluated for this Outcome. The Number Analyzed represented in each row differs from the Overall Number of Participants Analyzed as scores that are presented are for the participants who reported the measured event at the time evaluated. |
Arm/Group Title | Panobinostat |
---|---|
Arm/Group Description | Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible. |
Measure Participants | 35 |
Cycle 2, Day 1: Fatigue Right now |
0.0
(2.00)
|
Cycle 2, Day 1: Fatigue Usual Past 24 Hours |
0.5
(1.83)
|
Cycle 2, Day 1: Fatigue Worst Past 24 Hours |
0.7
(1.98)
|
Cycle 2, Day 1: General Activity |
0.0
(2.03)
|
Cycle 2, Day 1: Mood |
0.5
(2.15)
|
Cycle 2, Day 1: Walking Ability |
-0.6
(2.86)
|
Cycle 2, Day 1: Normal Work |
0.2
(2.87)
|
Cycle 2, Day 1: Relations with Other People |
-0.1
(2.71)
|
Cycle 2, Day 1: Enjoyment of Life |
0.3
(3.30)
|
Cycle 2, Day 1: Filling up quickly when you eat |
0.7
(2.38)
|
Cycle 2, Day 1: Abdominal Pain or Discomfort |
-0.0
(2.64)
|
Cycle 2, Day 1: Inactivity |
0.8
(2.45)
|
Cycle 2, Day 1: Cough |
-0.1
(2.07)
|
Cycle 2, Day 1: Night Sweats |
-1.0
(2.36)
|
Cycle 2, Day 1: Itching |
-1.5
(2.89)
|
Cycle 2, Day 1: Bone Pain |
-1.0
(2.79)
|
Cycle 2, Day 1: What is Overall Quality of Life? |
-0.4
(2.24)
|
Cycle 4, Day 1: Fatigue Right now |
0.0
(1.93)
|
Cycle 4, Day 1: Fatigue Usual Past 24 Hours |
0.8
(1.91)
|
Cycle 4, Day 1: Fatigue Worst Past 24 Hours |
1.0
(1.31)
|
Cycle 4, Day 1: General Activity |
-0.5
(3.07)
|
Cycle 4, Day 1: Mood |
0.3
(2.75)
|
Cycle 4, Day 1: Walking Ability |
-0.6
(3.26)
|
Cycle 4, Day 1: Normal Work |
0.9
(2.53)
|
Cycle 4, Day 1: Relations with Other People |
-0.6
(2.20)
|
Cycle 4, Day 1: Enjoyment of Life |
0.4
(3.62)
|
Cycle 4, Day 1: Filling up quickly when you eat |
-0.1
(4.42)
|
Cycle 4, Day 1: Abdominal Pain or Discomfort |
1.0
(2.67)
|
Cycle 4, Day 1: Inactivity |
0.6
(3.25)
|
Cycle 4, Day 1: Cough |
-0.9
(1.36)
|
Cycle 4, Day 1: Night Sweats |
-1.1
(3.52)
|
Cycle 4, Day 1: Itching |
-0.1
(0.90)
|
Cycle 4, Day 1: Bone Pain |
-1.8
(3.41)
|
Cycle 4, Day 1: What is Overall Quality of Life? |
-0.3
(1.60)
|
Title | Number of Participants With Adverse Events (AEs), and Serious Adverse Events (SAEs) |
---|---|
Description | An adverse event is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. SAEs was an undesirable sign, symptom or medical condition which is: life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, requires hospitalizations or prolongation of hospitalizations, or is medically significant |
Time Frame | AE: From the start of treatment up to 28 days after last study dose (up to approximately 2 years); SAE: From time of informed consent up to 4 weeks after last study dose (approximately 2 years) |
Outcome Measure Data
Analysis Population Description |
---|
Safety set population included all participants who received at least one dose of study drug and had at least one post-baseline safety assessment. |
Arm/Group Title | Panobinostat |
---|---|
Arm/Group Description | Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible. |
Measure Participants | 35 |
AEs |
35
100%
|
SAEs |
19
54.3%
|
Title | Monthly Capsule Counts to Assess Compliance to Panobinostat Treatment |
---|---|
Description | |
Time Frame | Up to approximately 2 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | To Compare the Response to Panobinostat in Patients With the JAK2 V617F Mutation to Those Without the JAK2 V617F Mutation |
---|---|
Description | |
Time Frame | Up to approximately 2 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | AE: From the start of treatment up to 28 days after last study dose (up to approximately 2 years); SAE: From time of informed consent up to 4 weeks after last study dose (approximately 2 years) | |
---|---|---|
Adverse Event Reporting Description | Safety set population included all participants who were randomized and received at least 1 dose of study drug. | |
Arm/Group Title | Panobinostat | |
Arm/Group Description | Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible. | |
All Cause Mortality |
||
Panobinostat | ||
Affected / at Risk (%) | # Events | |
Total | 1/35 (2.9%) | |
Serious Adverse Events |
||
Panobinostat | ||
Affected / at Risk (%) | # Events | |
Total | 19/35 (54.3%) | |
Blood and lymphatic system disorders | ||
Anaemia | 1/35 (2.9%) | |
Leukopenia | 1/35 (2.9%) | |
Neutropenia | 1/35 (2.9%) | |
Splenic infarction | 1/35 (2.9%) | |
Thrombocytopenia | 7/35 (20%) | |
Cardiac disorders | ||
Cardio-respiratory arrest | 1/35 (2.9%) | |
Gastrointestinal disorders | ||
Ascites | 1/35 (2.9%) | |
Diarrhoea | 1/35 (2.9%) | |
Diverticulum intestinal haemorrhagic | 1/35 (2.9%) | |
Gastritis haemorrhagic | 1/35 (2.9%) | |
Gastrointestinal haemorrhage | 1/35 (2.9%) | |
Nausea | 1/35 (2.9%) | |
Vomiting | 1/35 (2.9%) | |
General disorders | ||
Asthenia | 1/35 (2.9%) | |
Pyrexia | 2/35 (5.7%) | |
Infections and infestations | ||
Clostridium difficile colitis | 1/35 (2.9%) | |
Lobar pneumonia | 1/35 (2.9%) | |
Pneumonia | 2/35 (5.7%) | |
Sepsis | 1/35 (2.9%) | |
Urosepsis | 1/35 (2.9%) | |
Investigations | ||
Haemoglobin decreased | 1/35 (2.9%) | |
Metabolism and nutrition disorders | ||
Hypercalcaemia | 1/35 (2.9%) | |
Hypovolaemia | 1/35 (2.9%) | |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 1/35 (2.9%) | |
Bone pain | 1/35 (2.9%) | |
Psychiatric disorders | ||
Confusional state | 1/35 (2.9%) | |
Delirium | 1/35 (2.9%) | |
Renal and urinary disorders | ||
Renal failure acute | 1/35 (2.9%) | |
Respiratory, thoracic and mediastinal disorders | ||
Dyspnoea | 2/35 (5.7%) | |
Hypoxia | 1/35 (2.9%) | |
Interstitial lung disease | 1/35 (2.9%) | |
Vascular disorders | ||
Arterial haemorrhage | 1/35 (2.9%) | |
Hypotension | 1/35 (2.9%) | |
Orthostatic hypotension | 1/35 (2.9%) | |
Other (Not Including Serious) Adverse Events |
||
Panobinostat | ||
Affected / at Risk (%) | # Events | |
Total | 35/35 (100%) | |
Blood and lymphatic system disorders | ||
Anaemia | 10/35 (28.6%) | |
Leukopenia | 4/35 (11.4%) | |
Lymphopenia | 1/35 (2.9%) | |
Neutropenia | 6/35 (17.1%) | |
Thrombocytopenia | 18/35 (51.4%) | |
Cardiac disorders | ||
Acute myocardial infarction | 1/35 (2.9%) | |
Arrhythmia | 2/35 (5.7%) | |
Atrial fibrillation | 1/35 (2.9%) | |
Palpitations | 1/35 (2.9%) | |
Tachycardia | 2/35 (5.7%) | |
Endocrine disorders | ||
Cushingoid | 1/35 (2.9%) | |
Hypothyroidism | 2/35 (5.7%) | |
Eye disorders | ||
Eye haemorrhage | 1/35 (2.9%) | |
Lacrimation increased | 1/35 (2.9%) | |
Gastrointestinal disorders | ||
Abdominal discomfort | 1/35 (2.9%) | |
Abdominal distension | 6/35 (17.1%) | |
Abdominal pain | 7/35 (20%) | |
Abdominal pain lower | 1/35 (2.9%) | |
Abdominal pain upper | 1/35 (2.9%) | |
Ascites | 2/35 (5.7%) | |
Constipation | 8/35 (22.9%) | |
Diarrhoea | 27/35 (77.1%) | |
Dry mouth | 7/35 (20%) | |
Dyspepsia | 3/35 (8.6%) | |
Dysphagia | 1/35 (2.9%) | |
Faecal incontinence | 1/35 (2.9%) | |
Faeces discoloured | 1/35 (2.9%) | |
Flatulence | 1/35 (2.9%) | |
Gastrointestinal haemorrhage | 1/35 (2.9%) | |
Gastrointestinal pain | 1/35 (2.9%) | |
Haemorrhoids | 1/35 (2.9%) | |
Large intestinal haemorrhage | 1/35 (2.9%) | |
Mallory-Weiss syndrome | 1/35 (2.9%) | |
Melaena | 2/35 (5.7%) | |
Mouth haemorrhage | 1/35 (2.9%) | |
Nausea | 19/35 (54.3%) | |
Oesophageal haemorrhage | 1/35 (2.9%) | |
Rectal haemorrhage | 1/35 (2.9%) | |
Retching | 1/35 (2.9%) | |
Stomatitis | 1/35 (2.9%) | |
Toothache | 1/35 (2.9%) | |
Vomiting | 13/35 (37.1%) | |
General disorders | ||
Adverse drug reaction | 1/35 (2.9%) | |
Asthenia | 4/35 (11.4%) | |
Chills | 4/35 (11.4%) | |
Fatigue | 20/35 (57.1%) | |
Feeling jittery | 1/35 (2.9%) | |
General physical health deterioration | 1/35 (2.9%) | |
Generalised oedema | 1/35 (2.9%) | |
Mucosal inflammation | 1/35 (2.9%) | |
Oedema | 3/35 (8.6%) | |
Oedema peripheral | 6/35 (17.1%) | |
Pain | 2/35 (5.7%) | |
Pyrexia | 6/35 (17.1%) | |
Immune system disorders | ||
Drug hypersensitivity | 1/35 (2.9%) | |
Hypersensitivity | 1/35 (2.9%) | |
Infections and infestations | ||
Candidiasis | 1/35 (2.9%) | |
Clostridium difficile colitis | 1/35 (2.9%) | |
Furuncle | 1/35 (2.9%) | |
Herpes simplex | 1/35 (2.9%) | |
Oral candidiasis | 1/35 (2.9%) | |
Pneumonia | 1/35 (2.9%) | |
Staphylococcal infection | 1/35 (2.9%) | |
Subcutaneous abscess | 1/35 (2.9%) | |
Urinary tract infection | 2/35 (5.7%) | |
Investigations | ||
Blood alkaline phosphatase increased | 1/35 (2.9%) | |
Blood bilirubin increased | 1/35 (2.9%) | |
Blood creatinine increased | 4/35 (11.4%) | |
Blood magnesium decreased | 1/35 (2.9%) | |
Haemoglobin decreased | 2/35 (5.7%) | |
International normalised ratio increased | 1/35 (2.9%) | |
Vitamin D decreased | 1/35 (2.9%) | |
Weight decreased | 1/35 (2.9%) | |
Weight increased | 1/35 (2.9%) | |
White blood cell count increased | 1/35 (2.9%) | |
Metabolism and nutrition disorders | ||
Decreased appetite | 19/35 (54.3%) | |
Dehydration | 3/35 (8.6%) | |
Diabetes mellitus | 1/35 (2.9%) | |
Gout | 1/35 (2.9%) | |
Hypercalcaemia | 1/35 (2.9%) | |
Hyperglycaemia | 3/35 (8.6%) | |
Hypermagnesaemia | 1/35 (2.9%) | |
Hyperphosphataemia | 1/35 (2.9%) | |
Hyperuricaemia | 2/35 (5.7%) | |
Hypoalbuminaemia | 3/35 (8.6%) | |
Hypocalcaemia | 6/35 (17.1%) | |
Hypokalaemia | 4/35 (11.4%) | |
Hypomagnesaemia | 4/35 (11.4%) | |
Hyponatraemia | 3/35 (8.6%) | |
Hypophosphataemia | 4/35 (11.4%) | |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 1/35 (2.9%) | |
Back pain | 2/35 (5.7%) | |
Bone pain | 1/35 (2.9%) | |
Coccydynia | 1/35 (2.9%) | |
Facet joint syndrome | 1/35 (2.9%) | |
Flank pain | 3/35 (8.6%) | |
Joint swelling | 1/35 (2.9%) | |
Muscle spasms | 2/35 (5.7%) | |
Muscular weakness | 3/35 (8.6%) | |
Musculoskeletal pain | 1/35 (2.9%) | |
Myalgia | 1/35 (2.9%) | |
Neck pain | 3/35 (8.6%) | |
Pain in extremity | 3/35 (8.6%) | |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Lung neoplasm | 1/35 (2.9%) | |
Nervous system disorders | ||
Cognitive disorder | 1/35 (2.9%) | |
Dizziness | 7/35 (20%) | |
Dysarthria | 1/35 (2.9%) | |
Dysgeusia | 7/35 (20%) | |
Headache | 5/35 (14.3%) | |
Lethargy | 2/35 (5.7%) | |
Memory impairment | 1/35 (2.9%) | |
Peripheral sensory neuropathy | 1/35 (2.9%) | |
Sinus headache | 1/35 (2.9%) | |
Syncope | 3/35 (8.6%) | |
Psychiatric disorders | ||
Agitation | 2/35 (5.7%) | |
Anxiety | 2/35 (5.7%) | |
Confusional state | 1/35 (2.9%) | |
Hallucination | 1/35 (2.9%) | |
Insomnia | 2/35 (5.7%) | |
Psychotic disorder | 1/35 (2.9%) | |
Renal and urinary disorders | ||
Haematuria | 1/35 (2.9%) | |
Renal failure acute | 1/35 (2.9%) | |
Ureteric obstruction | 1/35 (2.9%) | |
Urinary incontinence | 3/35 (8.6%) | |
Urinary retention | 1/35 (2.9%) | |
Respiratory, thoracic and mediastinal disorders | ||
Atelectasis | 1/35 (2.9%) | |
Cough | 4/35 (11.4%) | |
Dyspnoea | 7/35 (20%) | |
Epistaxis | 4/35 (11.4%) | |
Haemoptysis | 1/35 (2.9%) | |
Hiccups | 1/35 (2.9%) | |
Oropharyngeal pain | 2/35 (5.7%) | |
Pleural effusion | 1/35 (2.9%) | |
Pleuritic pain | 1/35 (2.9%) | |
Productive cough | 2/35 (5.7%) | |
Pulmonary hypertension | 1/35 (2.9%) | |
Sinus congestion | 1/35 (2.9%) | |
Wheezing | 1/35 (2.9%) | |
Skin and subcutaneous tissue disorders | ||
Alopecia | 1/35 (2.9%) | |
Dermatitis exfoliative | 1/35 (2.9%) | |
Ecchymosis | 1/35 (2.9%) | |
Increased tendency to bruise | 2/35 (5.7%) | |
Night sweats | 2/35 (5.7%) | |
Petechiae | 3/35 (8.6%) | |
Purpura | 2/35 (5.7%) | |
Rash macular | 1/35 (2.9%) | |
Skin hyperpigmentation | 1/35 (2.9%) | |
Urticaria | 1/35 (2.9%) | |
Vascular disorders | ||
Flushing | 1/35 (2.9%) | |
Hypertension | 1/35 (2.9%) | |
Hypotension | 1/35 (2.9%) | |
Orthostatic hypotension | 1/35 (2.9%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Novartis Pharmaceuticals |
Phone | 862-778-8300 |
Novartis.email@novartis.com |
- CLBH589BUS58