Trial Outcomes & Findings for Study of Efficacy and Safety of LDE225 in Adult Patients With Relapsed/Refractory Acute Leukemia (NCT NCT01826214)
NCT ID: NCT01826214
Last Updated: 2016-08-30
Results Overview
Complete Response (CR) was based on the International Working Group (IWG) criteria based on weekly peripheral blood count measurements and bone marrow biopsy/aspiration collection. Efficacy assessments were performed to determine CR. A treatment cycle was defined as 4 weeks. The outcome measure for the study is based on standardized response criteria as defined by the International Working Group (IWG) for AML. The IWG was established by a group of investigators interested in the design and conduct of clinical trials in acute myeloid leukemia (AML). The criteria established by this group (a set of recommendations for response assessment) are well established, endorsed by major institutions and Health Authorities, and are widely used in clinical trials. No statistical analysis was planned for this primary outcome.
COMPLETED
PHASE2
70 participants
at screening, every week up to Week 9, every 2 weeks thereafter until CR, every 4 weeks after CR up to 24 months
2016-08-30
Participant Flow
35 patients were randomized but only 34 patients received at least one dose of study drug in the LDE225-800 (schedule B ) arm.
Participant milestones
| Measure |
LDE225-400
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
34
|
|
Overall Study
Untreated
|
0
|
1
|
|
Overall Study
Treated
|
35
|
34
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
35
|
34
|
Reasons for withdrawal
| Measure |
LDE225-400
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Overall Study
Adverse Event
|
7
|
6
|
|
Overall Study
Death
|
3
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
2
|
|
Overall Study
Progressive disease
|
22
|
21
|
|
Overall Study
Study terminated by Sponsor
|
0
|
1
|
|
Overall Study
Subject/guardian decision
|
2
|
3
|
Baseline Characteristics
Study of Efficacy and Safety of LDE225 in Adult Patients With Relapsed/Refractory Acute Leukemia
Baseline characteristics by cohort
| Measure |
LDE225-400
n=35 Participants
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=35 Participants
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.3 Years
STANDARD_DEVIATION 12.31 • n=99 Participants
|
67.7 Years
STANDARD_DEVIATION 11.65 • n=107 Participants
|
66.5 Years
STANDARD_DEVIATION 11.96 • n=206 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
31 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
39 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: at screening, every week up to Week 9, every 2 weeks thereafter until CR, every 4 weeks after CR up to 24 monthsPopulation: Full analysis set (FAS): comprised of all patients who were randomized to a study treatment. According to the intent-to-treat principle, patient data were analyzed according to the treatment to which they had been randomized. No statistical analysis were reported in this study.
Complete Response (CR) was based on the International Working Group (IWG) criteria based on weekly peripheral blood count measurements and bone marrow biopsy/aspiration collection. Efficacy assessments were performed to determine CR. A treatment cycle was defined as 4 weeks. The outcome measure for the study is based on standardized response criteria as defined by the International Working Group (IWG) for AML. The IWG was established by a group of investigators interested in the design and conduct of clinical trials in acute myeloid leukemia (AML). The criteria established by this group (a set of recommendations for response assessment) are well established, endorsed by major institutions and Health Authorities, and are widely used in clinical trials. No statistical analysis was planned for this primary outcome.
Outcome measures
| Measure |
LDE225-400
n=35 Participants
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=35 Participants
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Rate of Complete Remission (CR)
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: within 3 days after clearance of blasts from peripheral blood (PB), monthly thereafter until CR or reappearance of blasts in the PB, after CR every other month until discontination up to 24 monthsPopulation: Full analysis set (FAS): comprised of all patients who were randomized to a study treatment. According to the intent-to-treat principle, patient data were analyzed according to the treatment to which they had been randomized.
The other primary efficacy endpoint was CRi based on the International Working Group (IWG) criteria based on weekly peripheral blood count measurements and bone marrow biopsy/aspiration collection. Efficacy assessments were performed to determine CRi. A treatment cycle was defined as 4 weeks. No statistical analysis was planned for this primary outcome.
Outcome measures
| Measure |
LDE225-400
n=35 Participants
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=35 Participants
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Complete Remission With Incomplete Blood Count Recovery (CRi)
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Every 8 weeks for the first 6 months and every 12 weeks until 53 weeks after the last patient is enrolled or until relapse up to 24 monthsPopulation: Full analysis set (FAS): comprised of all patients who were randomized to a study treatment. According to the intent-to-treat principle, patient data were analyzed according to the treatment to which they had been randomized.
ORR was the rate of complete remission (CR), complete remission with incomplete blood count recovery (CRi) or partial response (PR) according to IWG criteria. CR, CRi or PR will be assessed through bone marrow biopsy/aspirate and peripheral blood blasts counts.
Outcome measures
| Measure |
LDE225-400
n=35 Participants
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=35 Participants
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Overall Response Rate (ORR)
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Week 1 Day 1, Week 9 Day 1Population: Pharmacokinetic analysis set (PAS): consisted of all patients who received at least one dose of sonidegib and provided at least one evaluable PK blood sample.
Cmax is the maximum observed plasma concentration after drug administration.The PK parameters were determined in plasma using non-compartmental methods. A PK sample was excluded from analyses if the patient vomited within the first 4 hours following the last oral dose of study drug. Other PK samples were excluded as deemed appropriate by the pharmacokineticist. Cmax was derived from the PK concentrations collected at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose on W1D1 and W9D1. The PK concentration at each time point is not an endpoint in the protocol, but these concentrations are used to derive the PK parameters.
Outcome measures
| Measure |
LDE225-400
n=29 Participants
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=33 Participants
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Parmacokintics (PK) Parameter: Cmax
Week 1 Day 1
|
237 ng/mL
Standard Deviation 158
|
343 ng/mL
Standard Deviation 275
|
|
Parmacokintics (PK) Parameter: Cmax
Week 9 Day 1(n: 7, 7)
|
1640 ng/mL
Standard Deviation 612
|
1500 ng/mL
Standard Deviation 874
|
SECONDARY outcome
Timeframe: Week 1 Day 1,Week 9 Day 1Population: Pharmacokinetic analysis set (PAS): consisted of all patients who received at least one dose of sonidegib and provided at least one evaluable PK blood sample.
Tmax is the time to reach Cmax. The PK parameters were determined in plasma using non-compartmental methods. A PK sample was excluded from analyses if the patient vomited within the first 4 hours following the last oral dose of study drug. Other PK samples were excluded as deemed appropriate by the Pharmacokineticist. Tmax was derived from the PK concentrations collected at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose on W1D1 and W9D1. The PK concentration at each time point is not an endpoint in the protocol, but these concentrations are used to derive the PK parameters.
Outcome measures
| Measure |
LDE225-400
n=29 Participants
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=33 Participants
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Parmacokintics (PK) Parameter: Tmax
Week 1 Day 1
|
2.13 hr
Inter-Quartile Range NA • Interval 1.0 to 8.08
|
2.12 hr
Inter-Quartile Range NA • Interval 1.0 to 8.0
|
|
Parmacokintics (PK) Parameter: Tmax
Week 9 Day 1 (n: 7, 7)
|
1.88 hr
Inter-Quartile Range NA • Interval 1.12 to 8.13
|
2.02 hr
Inter-Quartile Range NA • Interval 0.0 to 23.3
|
SECONDARY outcome
Timeframe: Week 1 Day 1,Week 9 Day 1Population: Pharmacokinetic analysis set (PAS): consisted of all patients who received at least one dose of sonidegib and provided at least one evaluable PK blood sample.
AUC0-8h is the area under the concentration-time curve from time zero to 8 hours. The PK parameters were determined in plasma using non-compartmental methods. A PK sample was excluded from analyses if the patient vomited within the first 4 hours following the last oral dose of study drug. Other PK samples were excluded as deemed appropriate by the Pharmacokineticist. AUC0-8h was derived from the PK concentrations collected at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose on W1D1 and W9D1. The PK concentration at each time point is not an endpoint in the protocol, but these concentrations are used to derive the PK parameters.
Outcome measures
| Measure |
LDE225-400
n=27 Participants
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=33 Participants
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Parmacokintics (PK) Parameter: AUC0-8h
Week 1 Day1
|
988 ng*hr/mL
Standard Deviation 542
|
1560 ng*hr/mL
Standard Deviation 1230
|
|
Parmacokintics (PK) Parameter: AUC0-8h
Week 9 Day1 (n: 7, 7)
|
9750 ng*hr/mL
Standard Deviation 2830
|
7910 ng*hr/mL
Standard Deviation 5090
|
SECONDARY outcome
Timeframe: Week 1 Day 1,Week 9 Day 1Population: Pharmacokinetic analysis set (PAS): consisted of all patients who received at least one dose of sonidegib and provided at least one evaluable PK blood sample.
AUC0-24 is the area under the concentration-time curve from time zero to 24 hours done only on 800 mg once a day schedule. The PK parameters were determined in plasma using non-compartmental methods. A PK sample was excluded from analyses if the patient vomited within the first 4 hours following the last oral dose of study drug. Other PK samples were excluded as deemed appropriate by the Pharmacokineticist. AUC0-24h was derived from the PK concentrations collected at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose on W1D1 and W9D1. The PK concentration at each time point is not an endpoint in the protocol, but these concentrations are used to derive the PK parameters.
Outcome measures
| Measure |
LDE225-400
n=7 Participants
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=32 Participants
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Parmacokintics (PK) Parameter: AUC0-24h
Week 1 Day 1
|
0 ng*hr/mL
Standard Deviation 0
|
3110 ng*hr/mL
Standard Deviation 2620
|
|
Parmacokintics (PK) Parameter: AUC0-24h
Week 9 Day 1 (n: 7, 6)
|
26500 ng*hr/mL
Standard Deviation 6650
|
24000 ng*hr/mL
Standard Deviation 11500
|
Adverse Events
LDE225-400
LDE225-800
Serious adverse events
| Measure |
LDE225-400
n=35 participants at risk
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=34 participants at risk
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.00%
0/35
|
5.9%
2/34
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
25.7%
9/35
|
20.6%
7/34
|
|
Blood and lymphatic system disorders
LEUKOCYTOSIS
|
2.9%
1/35
|
0.00%
0/34
|
|
Blood and lymphatic system disorders
PANCYTOPENIA
|
2.9%
1/35
|
0.00%
0/34
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/35
|
2.9%
1/34
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
2.9%
1/35
|
0.00%
0/34
|
|
Gastrointestinal disorders
COLITIS
|
0.00%
0/35
|
2.9%
1/34
|
|
Gastrointestinal disorders
CONSTIPATION
|
2.9%
1/35
|
0.00%
0/34
|
|
Gastrointestinal disorders
DIARRHOEA
|
2.9%
1/35
|
0.00%
0/34
|
|
Gastrointestinal disorders
GASTRIC HAEMORRHAGE
|
0.00%
0/35
|
2.9%
1/34
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/35
|
2.9%
1/34
|
|
Gastrointestinal disorders
GINGIVAL HYPERTROPHY
|
2.9%
1/35
|
0.00%
0/34
|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/35
|
2.9%
1/34
|
|
Gastrointestinal disorders
OESOPHAGEAL ULCER
|
2.9%
1/35
|
0.00%
0/34
|
|
Gastrointestinal disorders
STOMATITIS
|
0.00%
0/35
|
2.9%
1/34
|
|
Gastrointestinal disorders
VOMITING
|
0.00%
0/35
|
2.9%
1/34
|
|
General disorders
ASTHENIA
|
5.7%
2/35
|
2.9%
1/34
|
|
General disorders
FATIGUE
|
2.9%
1/35
|
2.9%
1/34
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
11.4%
4/35
|
2.9%
1/34
|
|
General disorders
MULTI-ORGAN FAILURE
|
2.9%
1/35
|
0.00%
0/34
|
|
General disorders
PYREXIA
|
2.9%
1/35
|
11.8%
4/34
|
|
Infections and infestations
ANAL ABSCESS
|
0.00%
0/35
|
2.9%
1/34
|
|
Infections and infestations
ARTHRITIS INFECTIVE
|
2.9%
1/35
|
0.00%
0/34
|
|
Infections and infestations
BACTERAEMIA
|
0.00%
0/35
|
2.9%
1/34
|
|
Infections and infestations
CLOSTRIDIAL INFECTION
|
2.9%
1/35
|
0.00%
0/34
|
|
Infections and infestations
DEVICE RELATED INFECTION
|
2.9%
1/35
|
0.00%
0/34
|
|
Infections and infestations
ENTEROCOCCAL BACTERAEMIA
|
2.9%
1/35
|
0.00%
0/34
|
|
Infections and infestations
EPIGLOTTITIS
|
2.9%
1/35
|
0.00%
0/34
|
|
Infections and infestations
INFECTION
|
2.9%
1/35
|
0.00%
0/34
|
|
Infections and infestations
INFLUENZA
|
2.9%
1/35
|
0.00%
0/34
|
|
Infections and infestations
LUNG INFECTION
|
5.7%
2/35
|
0.00%
0/34
|
|
Infections and infestations
NEUTROPENIC INFECTION
|
2.9%
1/35
|
0.00%
0/34
|
|
Infections and infestations
PNEUMONIA
|
8.6%
3/35
|
8.8%
3/34
|
|
Infections and infestations
SEPSIS
|
5.7%
2/35
|
11.8%
4/34
|
|
Infections and infestations
STAPHYLOCOCCAL SEPSIS
|
2.9%
1/35
|
0.00%
0/34
|
|
Infections and infestations
URINARY TRACT INFECTION
|
2.9%
1/35
|
0.00%
0/34
|
|
Injury, poisoning and procedural complications
FALL
|
0.00%
0/35
|
2.9%
1/34
|
|
Injury, poisoning and procedural complications
SUBDURAL HAEMORRHAGE
|
0.00%
0/35
|
2.9%
1/34
|
|
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED
|
5.7%
2/35
|
5.9%
2/34
|
|
Investigations
MYOGLOBIN BLOOD INCREASED
|
2.9%
1/35
|
0.00%
0/34
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
2.9%
1/35
|
0.00%
0/34
|
|
Metabolism and nutrition disorders
FLUID OVERLOAD
|
0.00%
0/35
|
2.9%
1/34
|
|
Metabolism and nutrition disorders
GOUT
|
0.00%
0/35
|
2.9%
1/34
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
5.7%
2/35
|
0.00%
0/34
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
0.00%
0/35
|
2.9%
1/34
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
2.9%
1/35
|
0.00%
0/34
|
|
Musculoskeletal and connective tissue disorders
MYOPATHY
|
0.00%
0/35
|
2.9%
1/34
|
|
Musculoskeletal and connective tissue disorders
OSTEONECROSIS OF JAW
|
2.9%
1/35
|
0.00%
0/34
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN
|
0.00%
0/35
|
2.9%
1/34
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LEUKAEMIC INFILTRATION
|
2.9%
1/35
|
0.00%
0/34
|
|
Nervous system disorders
CEREBRAL HAEMORRHAGE
|
2.9%
1/35
|
2.9%
1/34
|
|
Nervous system disorders
DYSGEUSIA
|
0.00%
0/35
|
2.9%
1/34
|
|
Nervous system disorders
HAEMORRHAGE INTRACRANIAL
|
0.00%
0/35
|
2.9%
1/34
|
|
Nervous system disorders
QUADRIPLEGIA
|
0.00%
0/35
|
2.9%
1/34
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
2.9%
1/35
|
5.9%
2/34
|
|
Respiratory, thoracic and mediastinal disorders
IDIOPATHIC PNEUMONIA SYNDROME
|
2.9%
1/35
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
LARYNGEAL INFLAMMATION
|
0.00%
0/35
|
2.9%
1/34
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.00%
0/35
|
2.9%
1/34
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
2.9%
1/35
|
0.00%
0/34
|
|
Vascular disorders
CIRCULATORY COLLAPSE
|
0.00%
0/35
|
2.9%
1/34
|
Other adverse events
| Measure |
LDE225-400
n=35 participants at risk
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
LDE225-800
n=34 participants at risk
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
|
|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
14.3%
5/35
|
17.6%
6/34
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
8.6%
3/35
|
5.9%
2/34
|
|
Blood and lymphatic system disorders
LEUKOCYTOSIS
|
2.9%
1/35
|
11.8%
4/34
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
5.7%
2/35
|
8.8%
3/34
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
8.6%
3/35
|
5.9%
2/34
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
20.0%
7/35
|
14.7%
5/34
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
2.9%
1/35
|
5.9%
2/34
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
11.4%
4/35
|
8.8%
3/34
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
5.7%
2/35
|
2.9%
1/34
|
|
Gastrointestinal disorders
APHTHOUS STOMATITIS
|
0.00%
0/35
|
5.9%
2/34
|
|
Gastrointestinal disorders
CONSTIPATION
|
17.1%
6/35
|
23.5%
8/34
|
|
Gastrointestinal disorders
DIARRHOEA
|
20.0%
7/35
|
23.5%
8/34
|
|
Gastrointestinal disorders
DYSPEPSIA
|
8.6%
3/35
|
8.8%
3/34
|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.00%
0/35
|
5.9%
2/34
|
|
Gastrointestinal disorders
GINGIVAL BLEEDING
|
0.00%
0/35
|
8.8%
3/34
|
|
Gastrointestinal disorders
HAEMORRHOIDS
|
5.7%
2/35
|
2.9%
1/34
|
|
Gastrointestinal disorders
MOUTH HAEMORRHAGE
|
0.00%
0/35
|
8.8%
3/34
|
|
Gastrointestinal disorders
MOUTH ULCERATION
|
5.7%
2/35
|
2.9%
1/34
|
|
Gastrointestinal disorders
NAUSEA
|
31.4%
11/35
|
29.4%
10/34
|
|
Gastrointestinal disorders
ORAL DISORDER
|
5.7%
2/35
|
0.00%
0/34
|
|
Gastrointestinal disorders
ORAL PAIN
|
2.9%
1/35
|
8.8%
3/34
|
|
Gastrointestinal disorders
VOMITING
|
20.0%
7/35
|
35.3%
12/34
|
|
General disorders
ASTHENIA
|
2.9%
1/35
|
5.9%
2/34
|
|
General disorders
CHILLS
|
5.7%
2/35
|
0.00%
0/34
|
|
General disorders
FATIGUE
|
22.9%
8/35
|
29.4%
10/34
|
|
General disorders
FEELING COLD
|
5.7%
2/35
|
0.00%
0/34
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
2.9%
1/35
|
8.8%
3/34
|
|
General disorders
MALAISE
|
2.9%
1/35
|
5.9%
2/34
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.00%
0/35
|
5.9%
2/34
|
|
General disorders
OEDEMA PERIPHERAL
|
11.4%
4/35
|
14.7%
5/34
|
|
General disorders
PAIN
|
0.00%
0/35
|
8.8%
3/34
|
|
General disorders
PYREXIA
|
20.0%
7/35
|
29.4%
10/34
|
|
Infections and infestations
INFECTION
|
0.00%
0/35
|
5.9%
2/34
|
|
Infections and infestations
NASOPHARYNGITIS
|
2.9%
1/35
|
5.9%
2/34
|
|
Infections and infestations
ORAL HERPES
|
5.7%
2/35
|
2.9%
1/34
|
|
Infections and infestations
SKIN INFECTION
|
5.7%
2/35
|
2.9%
1/34
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
0.00%
0/35
|
8.8%
3/34
|
|
Infections and infestations
URINARY TRACT INFECTION
|
2.9%
1/35
|
5.9%
2/34
|
|
Injury, poisoning and procedural complications
FALL
|
0.00%
0/35
|
5.9%
2/34
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
5.7%
2/35
|
2.9%
1/34
|
|
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED
|
22.9%
8/35
|
20.6%
7/34
|
|
Investigations
BLOOD CREATININE INCREASED
|
2.9%
1/35
|
14.7%
5/34
|
|
Investigations
BLOOD MAGNESIUM DECREASED
|
2.9%
1/35
|
5.9%
2/34
|
|
Investigations
MYOGLOBIN BLOOD INCREASED
|
5.7%
2/35
|
0.00%
0/34
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
2.9%
1/35
|
5.9%
2/34
|
|
Investigations
PLATELET COUNT DECREASED
|
5.7%
2/35
|
5.9%
2/34
|
|
Investigations
WEIGHT DECREASED
|
5.7%
2/35
|
5.9%
2/34
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
2.9%
1/35
|
5.9%
2/34
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
20.0%
7/35
|
14.7%
5/34
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
0.00%
0/35
|
8.8%
3/34
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
5.7%
2/35
|
0.00%
0/34
|
|
Metabolism and nutrition disorders
HYPOCALCAEMIA
|
8.6%
3/35
|
0.00%
0/34
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
11.4%
4/35
|
17.6%
6/34
|
|
Metabolism and nutrition disorders
HYPOMAGNESAEMIA
|
0.00%
0/35
|
5.9%
2/34
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
8.6%
3/35
|
5.9%
2/34
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
5.7%
2/35
|
5.9%
2/34
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
22.9%
8/35
|
14.7%
5/34
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
2.9%
1/35
|
5.9%
2/34
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
2.9%
1/35
|
5.9%
2/34
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
11.4%
4/35
|
23.5%
8/34
|
|
Musculoskeletal and connective tissue disorders
MYOPATHY
|
5.7%
2/35
|
0.00%
0/34
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
2.9%
1/35
|
11.8%
4/34
|
|
Nervous system disorders
DIZZINESS
|
5.7%
2/35
|
14.7%
5/34
|
|
Nervous system disorders
DYSGEUSIA
|
8.6%
3/35
|
14.7%
5/34
|
|
Nervous system disorders
HEADACHE
|
8.6%
3/35
|
14.7%
5/34
|
|
Psychiatric disorders
ANXIETY
|
11.4%
4/35
|
0.00%
0/34
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
11.4%
4/35
|
0.00%
0/34
|
|
Psychiatric disorders
INSOMNIA
|
5.7%
2/35
|
5.9%
2/34
|
|
Renal and urinary disorders
DYSURIA
|
5.7%
2/35
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
8.6%
3/35
|
11.8%
4/34
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
20.0%
7/35
|
17.6%
6/34
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
11.4%
4/35
|
8.8%
3/34
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
2.9%
1/35
|
5.9%
2/34
|
|
Respiratory, thoracic and mediastinal disorders
PRODUCTIVE COUGH
|
0.00%
0/35
|
8.8%
3/34
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
5.7%
2/35
|
0.00%
0/34
|
|
Skin and subcutaneous tissue disorders
NIGHT SWEATS
|
0.00%
0/35
|
5.9%
2/34
|
|
Skin and subcutaneous tissue disorders
PETECHIAE
|
2.9%
1/35
|
17.6%
6/34
|
|
Skin and subcutaneous tissue disorders
RASH
|
11.4%
4/35
|
5.9%
2/34
|
|
Skin and subcutaneous tissue disorders
SKIN LESION
|
5.7%
2/35
|
0.00%
0/34
|
|
Vascular disorders
HAEMATOMA
|
0.00%
0/35
|
5.9%
2/34
|
|
Vascular disorders
HYPERTENSION
|
0.00%
0/35
|
5.9%
2/34
|
|
Vascular disorders
ORTHOSTATIC HYPOTENSION
|
5.7%
2/35
|
0.00%
0/34
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER