GEPARD: LBH589 Alone or in Combination With Erythropoietin Stimulating Agents (ESA) in Patients With Low or Int-1 Risk Myelodysplastic Syndromes (MDS)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01034657
• Collaborator: (none)
• Enrollment: 34
• Locations: 12
• Arms: 2
• Duration (Months): 33
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study assessed the efficacy and safety of LBH589 as single agent and in combination with ESA in red blood cell transfusion-dependent Low and Int-1 MDS patients being either refractory to ESA or with a low probability of response. The study had a non-randomized core phase followed by a randomized phase.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome (MDS)	Drug: LBH589; Drug: Epoetin Alfa	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A One Year, Open Label, Multicenter Trial of LBH589 Alone or in Combination With ESA in Red Blood Cell Transfusion-dependent LOW and INT-1 MDS Patients Being Either Refractory to ESA or With a Low Probability of Response - the GErman PAnobinostat Low Risk MDS Trial - GEPARD Study
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LBH589 During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	Drug: LBH589; LBH589 was supplied at dose strengths of 5 mg or 20 mg hard gelatin capsules.; Other Names: Panobinostat
Experimental: LBH589 + Epoetin Alfa During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Drug: LBH589; LBH589 was supplied at dose strengths of 5 mg or 20 mg hard gelatin capsules.; Other Names: Panobinostat ; Drug: Epoetin Alfa; Epoetin alfa was supplied as 10000 IU/1 mL in a ready-to-use syringe.; Other Names: ESA, HEXAL®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Hematological Response of the Erythropoetic System (HI-E) - Core Phase [16 weeks]

   HI-E was assessed according to the modified international working group (IWG) criteria for HI. Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk, and only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response evaluation; Platelet response (pretreatment, < 100 x 109/L): absolute increase of ≥ 30 x 109/L for participants starting with > 20 x 109/L and platelets Increase from < 20 x 109/L to > 20 x 109/L and by at least 100%; Neutrophil response (pretreatment, < 1.0 x 109/L): at least 100% increase and an absolute increase > 0.5 x 109/L; Progression or relapse after HI: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets, reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.

Secondary Outcome Measures

1. Percentage of Participants With HI-E - Randomized Phase [32 weeks, 52 weeks]

   HI-E was assessed according to the modified international working group (IWG) criteria for HI. Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk, and only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response evaluation; Platelet response (pretreatment, < 100 x 109/L): absolute increase of ≥ 30 x 109/L for participants starting with > 20 x 109/L and platelets Increase from < 20 x 109/L to > 20 x 109/L and by at least 100%; Neutrophil response (pretreatment, < 1.0 x 109/L): at least 100% increase and an absolute increase > 0.5 x 109/L; Progression or relapse after HI: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets, reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.

2. Percentage of Participants With Objective Response During Core Phase [16 weeks]

   Objective response (complete remission (CR) + partial remission (PR) and HI-platelet (HI-P) response + HI-neutrophil (HI-N) response) was assessed according to the modified IWG criteria: CR bone marrow with 5% myeloblasts with normal maturation of al cell lines (persistent dysplasia is noted) and peripheral blood with Hgb >= 11 g/dL platelets >=100 X 10^9/L, neutrophils >= 1.0 x 10^9/L and blasts 0%. PR = All CR if abnormal before treatment except bone marrow blasts decreased by>=50% over pretreatment but still >5% (ellularity and morphology not relevant). HI-P (pretreatment, < 100 x 109/L) = absolute increase of ≥ 30 x 109/L for participants starting with > 20 x 109/L and platelets Increase from < 20 x 109/L to > 20 x 109/L and by at least 100%; HI-N (pretreatment, < 1.0 x 109/L) = at least 100% increase and an absolute increase > 0.5 x 10^9/L.

3. Percentage of Participants With Objective Response During the Randomized Phase [32 weeks, 48 weeks]

   Objective response (complete remission (CR) + partial remission (PR) and HI-platelet (HI-P) response + HI-neutrophil (HI-N) response) was assessed according to the modified IWG criteria: CR bone marrow with 5% myeloblasts with normal maturation of al cell lines (persistent dysplasia is noted) and peripheral blood with Hgb >= 11 g/dL platelets >=100 X 10^9/L, neutrophils >= 1.0 x 10^9/L and blasts 0%. PR = All CR if abnormal before treatment except bone marrow blasts decreased by>=50% over pretreatment but still >5% (ellularity and morphology not relevant). HI-P (pretreatment, < 100 x 109/L) = absolute increase of ≥ 30 x 109/L for participants starting with > 20 x 109/L and platelets Increase from < 20 x 109/L to > 20 x 109/L and by at least 100%; HI-N (pretreatment, < 1.0 x 109/L) = at least 100% increase and an absolute increase > 0.5 x 10^9/L.

4. Frequency Distribution of IPSS Score Status - Core Phase [baseline]

   The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).

5. Frequency Distribution of IPSS Score Status - Randomized Phase [52 weeks]

   The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).

6. Mean Single Scoring Values of the IPSS - Core Phase [baseline]

   The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).

7. Mean Single Scoring Values of the IPSS - Randomized Phase [52 weeks]

   The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).

8. Overall Survival (OS) - Overall Period [48 weeks]

   OS was defined as the time from start of treatment to death from any cause.

9. Time to Response - Overall Period [52 weeks]

   Time to response was defined as the time from start of treatment to the first documented response (complete [CR] or partial [PR]) according to modified IWG criteria for HI.

10. Event-free Survival (EFS) - Overall Period [52 weeks]

    EFS was defined as the time from start of treatment to failure or death from any cause.

11. Progression-free Survival (PFS) - Overall Period [52 weeks]

    PFS was defined as the time from start of treatment to disease progression or death from MDS.

12. Disease-free Survival (DFS) - Overall Period [52 weeks]

    DFS was defined as the time from start of treatment to the time to relapse.

13. Time to Cause-specific Death - Overall Period [52 weeks]

    Time to cause-specific death was defined as the time from start of treatment to death related to MDS.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Patients with a lower risk MDS (LOW or INT-1 according to IPSS)

• Red blood cell transfusion dependency of at least 4 Units/8 weeks.

• Not responding to Erythropoietin stimulating agents (ESA) or having a low chance to do so

• Age-adjusted normal cardiac, kidney, liver function

Key Exclusion Criteria:

• Concomitant use of ESA

• Concomitant use of any other investigational drug

• Other malignancy that is not in remission for at least 1 year

• Platelet Count < 75 x 109/L

• Impaired cardiac function or clinically significant cardiac diseases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Mannheim	Baden-Württemberg	Germany	68305
2	Novartis Investigative Site	Berlin		Germany	12203
3	Novartis Investigative Site	Bonn		Germany	53105
4	Novartis Investigative Site	Dresden		Germany	01307
5	Novartis Investigative Site	Duesseldorf		Germany	40225
6	Novartis Investigative Site	Duisburg		Germany	47166
7	Novartis Investigative Site	Frankfurt		Germany	60590
8	Novartis Investigative Site	Goettingen		Germany	37075
9	Novartis Investigative Site	Hannover		Germany	30625
10	Novartis Investigative Site	Leipzig		Germany	04103
11	Novartis Investigative Site	Muenchen		Germany	81675
12	Novartis Investigative Site	Ulm		Germany	89081

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01034657
• Other Study ID Numbers: CLBH589BDE04; EudraCT 2009-010403-84; 2009-010403-84
• First Posted: Dec 17, 2009
• Last Update Posted: Aug 11, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Novartis Pharmaceuticals: MDS; bone marrow; anemia; cytopenia; transfusion dependance; EPO; ESA; erythropoietin; LBH589; Myelodysplastic Syndromes; hematopoietic improvement; IPSS Low; IPSS Int-1; HI-E; HDAC Inhibitor; HDAC-I; DAC-I; Deacetylase-Inhibitor; Histone Deacetylase-Inhibitor; red blood cell transfusions
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Panobinostat; Epoetin Alfa

Study Results

Participant Flow

Recruitment Details	The study was divided into a core phase and a randomized phase. The core phase had an open-label single arm study design. The randomized phase was open-label with two parallel treatment arms for participants with stable disease. Participants with Hematological response of the erythropoietin system remained on single agent oral LBH589.
Pre-assignment Detail	Participants with stable disease were eligible for randomization to single agent LBH589 or LBH589 + epoetin alfa. Participants with progressive disease were discontinued. Seven participants who completed the core phase withdrew before the randomization phase.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
Period Title: Core Phase
STARTED	34	0	0
COMPLETED	20	0	0
NOT COMPLETED	14	0	0
Period Title: Core Phase
STARTED	6	6	1
COMPLETED	1	0	0
NOT COMPLETED	5	6	1

Baseline Characteristics

Arm/Group Title	LBH589
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.
Overall Participants	34
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.4 (7.70)
Sex: Female, Male (Count of Participants)
Female	10 29.4%
Male	24 70.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Hematological Response of the Erythropoetic System (HI-E) - Core Phase
Description	HI-E was assessed according to the modified international working group (IWG) criteria for HI. Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk, and only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response evaluation; Platelet response (pretreatment, < 100 x 109/L): absolute increase of ≥ 30 x 109/L for participants starting with > 20 x 109/L and platelets Increase from < 20 x 109/L to > 20 x 109/L and by at least 100%; Neutrophil response (pretreatment, < 1.0 x 109/L): at least 100% increase and an absolute increase > 0.5 x 109/L; Progression or relapse after HI: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets, reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Participants from the core phase, who had valid response data, were analyzed.

Arm/Group Title	LBH589
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.
Measure Participants	20
Number [Percentage of participants]	0.0 0%

2. Secondary Outcome

Title	Percentage of Participants With HI-E - Randomized Phase
Description	HI-E was assessed according to the modified international working group (IWG) criteria for HI. Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk, and only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response evaluation; Platelet response (pretreatment, < 100 x 109/L): absolute increase of ≥ 30 x 109/L for participants starting with > 20 x 109/L and platelets Increase from < 20 x 109/L to > 20 x 109/L and by at least 100%; Neutrophil response (pretreatment, < 1.0 x 109/L): at least 100% increase and an absolute increase > 0.5 x 109/L; Progression or relapse after HI: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets, reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.
Time Frame	32 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants from the randomized phase, who had valid response data, were analyzed.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
Measure Participants	6	6	1
32 weeks (n=5,1,1)	0.0 0%	0.0 NaN	0.0 NaN
52 weeks (n=4,3,1)	0.0 0%	0.0 NaN	0.0 NaN

3. Secondary Outcome

Title	Percentage of Participants With Objective Response During Core Phase
Description	Objective response (complete remission (CR) + partial remission (PR) and HI-platelet (HI-P) response + HI-neutrophil (HI-N) response) was assessed according to the modified IWG criteria: CR bone marrow with 5% myeloblasts with normal maturation of al cell lines (persistent dysplasia is noted) and peripheral blood with Hgb >= 11 g/dL platelets >=100 X 10^9/L, neutrophils >= 1.0 x 10^9/L and blasts 0%. PR = All CR if abnormal before treatment except bone marrow blasts decreased by>=50% over pretreatment but still >5% (ellularity and morphology not relevant). HI-P (pretreatment, < 100 x 109/L) = absolute increase of ≥ 30 x 109/L for participants starting with > 20 x 109/L and platelets Increase from < 20 x 109/L to > 20 x 109/L and by at least 100%; HI-N (pretreatment, < 1.0 x 109/L) = at least 100% increase and an absolute increase > 0.5 x 10^9/L.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Participants from the core phase, who had valid data, were analyzed.

Arm/Group Title	LBH589
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.
Measure Participants	20
Number [Percentage of participants]	0.0 0%

4. Secondary Outcome

Title	Percentage of Participants With Objective Response During the Randomized Phase
Description	Objective response (complete remission (CR) + partial remission (PR) and HI-platelet (HI-P) response + HI-neutrophil (HI-N) response) was assessed according to the modified IWG criteria: CR bone marrow with 5% myeloblasts with normal maturation of al cell lines (persistent dysplasia is noted) and peripheral blood with Hgb >= 11 g/dL platelets >=100 X 10^9/L, neutrophils >= 1.0 x 10^9/L and blasts 0%. PR = All CR if abnormal before treatment except bone marrow blasts decreased by>=50% over pretreatment but still >5% (ellularity and morphology not relevant). HI-P (pretreatment, < 100 x 109/L) = absolute increase of ≥ 30 x 109/L for participants starting with > 20 x 109/L and platelets Increase from < 20 x 109/L to > 20 x 109/L and by at least 100%; HI-N (pretreatment, < 1.0 x 109/L) = at least 100% increase and an absolute increase > 0.5 x 10^9/L.
Time Frame	32 weeks, 48 weeks

Outcome Measure Data

Analysis Population Description

Participants from the randomized phase, who had valid data, were analyzed.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
Measure Participants	6	6	1
Week 32 ( n=5,1,1)	0.0 0%	0.0 NaN	0.0 NaN
Week 48 (n=6,5,1)	0.0 0%	0.0 NaN	0.0 NaN

5. Secondary Outcome

Title	Frequency Distribution of IPSS Score Status - Core Phase
Description	The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

All participants from the core phase were analyzed.

Arm/Group Title	LBH589
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.
Measure Participants	34
Baseline (core phase), Low	32.4 95.3%
Baseline (core phase),, INT-1	67.6 198.8%
Baseline (core phase),, INT-2	0.0 0%
Baseline (core phase), High	0.0 0%

6. Secondary Outcome

Title	Frequency Distribution of IPSS Score Status - Randomized Phase
Description	The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Only participants from the randomized phase, who had values at week 52, were included in the analysis.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
Measure Participants	6	6	1
Week 52 (randomized phase), Low	0.0 0%	0.0 NaN	100.0 NaN
Week 52 (randomized phase), , INT-1	16.7 49.1%	16.7 NaN	0.0 NaN
Week 52 (randomized phase), INT-2	0.0 0%	0.0 NaN	0.0 NaN
Week 52 (randomized phase), HIgh	0.0 0%	0.0 NaN	0.0 NaN

7. Secondary Outcome

Title	Mean Single Scoring Values of the IPSS - Core Phase
Description	The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

All participants from the core phase were analyzed.

Arm/Group Title	LBH589
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.
Measure Participants	34
Mean (Standard Deviation) [units on a scale]	0.43 (0.351)

8. Secondary Outcome

Title	Mean Single Scoring Values of the IPSS - Randomized Phase
Description	The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast <5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex >= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high >=2.5 points (6 months of median survival).
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Participants from the randomized phase, who had values at week 52, were included in the analysis.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.
Measure Participants	1	1	1
Mean (Standard Deviation) [units on a scale]	1.0 (NA)	1.0 (NA)	0.0 (NA)

9. Secondary Outcome

Title	Overall Survival (OS) - Overall Period
Description	OS was defined as the time from start of treatment to death from any cause.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

All participants from the core phase were analyzed.

Arm/Group Title	LBH589
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.
Measure Participants	34
Median (90% Confidence Interval) [months]	NA

10. Secondary Outcome

Title	Time to Response - Overall Period
Description	Time to response was defined as the time from start of treatment to the first documented response (complete [CR] or partial [PR]) according to modified IWG criteria for HI.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Time to response could not be evaluated because there was no response.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
Measure Participants	0	0	0

11. Secondary Outcome

Title	Event-free Survival (EFS) - Overall Period
Description	EFS was defined as the time from start of treatment to failure or death from any cause.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Event-free survival could not be evaluated because there was no response, no progression or no disease-free period.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
Measure Participants	0	0	0

12. Secondary Outcome

Title	Progression-free Survival (PFS) - Overall Period
Description	PFS was defined as the time from start of treatment to disease progression or death from MDS.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

PFS could not be evaluated because there was no progression.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
Measure Participants	0	0	0

13. Secondary Outcome

Title	Disease-free Survival (DFS) - Overall Period
Description	DFS was defined as the time from start of treatment to the time to relapse.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

DFS could not be evaluated because there was no disease-free period.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
Measure Participants	0	0	0

14. Secondary Outcome

Title	Time to Cause-specific Death - Overall Period
Description	Time to cause-specific death was defined as the time from start of treatment to death related to MDS.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Time to cause-specific death could not be evaluated because there was no cause-specific death.

Arm/Group Title	LBH589	LBH589 + Epoetin Alfa	Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.	During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.	Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
Measure Participants	0	0	0

Adverse Events

Arm/Group Title	LBH589 - Core Phase		LBH589 - Randomized Phase		LBH589 + ESA - Randomized Phase		Not Randomized
Arm/Group Description	During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.		During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.		During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.		Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.
All Cause Mortality
	LBH589 - Core Phase		LBH589 - Randomized Phase		LBH589 + ESA - Randomized Phase		Not Randomized
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LBH589 - Core Phase		LBH589 - Randomized Phase		LBH589 + ESA - Randomized Phase		Not Randomized
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/34 (32.4%)		1/6 (16.7%)		1/6 (16.7%)		1/1 (100%)
Cardiac disorders
Coronary artery stenosis	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Myocardial infarction	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Ear and labyrinth disorders
Sudden hearing loss	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Eye disorders
Optic ischaemic neuropathy	0/34 (0%)		0/6 (0%)		0/6 (0%)		1/1 (100%)
Gastrointestinal disorders
Diarrhoea	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Faecaloma	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Vomiting	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
General disorders
Chest pain	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Impaired healing	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Pyrexia	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Infections and infestations
Abscess limb	0/34 (0%)		0/6 (0%)		1/6 (16.7%)		0/1 (0%)
Lymph node abscess	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Pneumonia	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Postoperative wound infection	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Sepsis	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Septic shock	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Staphylococcal infection	0/34 (0%)		0/6 (0%)		1/6 (16.7%)		0/1 (0%)
Subcutaneous abscess	0/34 (0%)		0/6 (0%)		1/6 (16.7%)		0/1 (0%)
Metabolism and nutrition disorders
Dehydration	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Rhabdomyolysis	0/34 (0%)		0/6 (0%)		0/6 (0%)		1/1 (100%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myelomonocytic leukaemia	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Renal and urinary disorders
Glomerulonephritis	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Haematuria	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Urinary incontinence	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Pulmonary embolism	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Vascular disorders
Phlebitis	0/34 (0%)		0/6 (0%)		1/6 (16.7%)		0/1 (0%)
Vascular pseudoaneurysm	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	LBH589 - Core Phase		LBH589 - Randomized Phase		LBH589 + ESA - Randomized Phase		Not Randomized
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/34 (100%)		6/6 (100%)		6/6 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Anaemia	3/34 (8.8%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Leukopenia	4/34 (11.8%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Neutropenia	12/34 (35.3%)		1/6 (16.7%)		1/6 (16.7%)		0/1 (0%)
Thrombocytopenia	14/34 (41.2%)		1/6 (16.7%)		1/6 (16.7%)		0/1 (0%)
Ear and labyrinth disorders
Vertigo	5/34 (14.7%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Endocrine disorders
Hypothyroidism	6/34 (17.6%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Gastrointestinal disorders
Abdominal pain	3/34 (8.8%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Abdominal pain upper	3/34 (8.8%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Cheilitis	2/34 (5.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Constipation	3/34 (8.8%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Diarrhoea	24/34 (70.6%)		1/6 (16.7%)		3/6 (50%)		0/1 (0%)
Dyspepsia	5/34 (14.7%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Nausea	18/34 (52.9%)		1/6 (16.7%)		1/6 (16.7%)		0/1 (0%)
Stomach discomfort	2/34 (5.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Stomatitis	2/34 (5.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Teeth brittle	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		1/1 (100%)
Vomiting	9/34 (26.5%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
General disorders
Asthenia	7/34 (20.6%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Fatigue	16/34 (47.1%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Gait disturbance	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Influenza like illness	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Oedema peripheral	2/34 (5.9%)		3/6 (50%)		1/6 (16.7%)		0/1 (0%)
Pyrexia	2/34 (5.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Immune system disorders
Hypersensitivity	2/34 (5.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Infections and infestations
Abdominal wall abscess	0/34 (0%)		0/6 (0%)		0/6 (0%)		1/1 (100%)
Bronchitis	2/34 (5.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Nasopharyngitis	3/34 (8.8%)		1/6 (16.7%)		1/6 (16.7%)		0/1 (0%)
Urinary tract infection	2/34 (5.9%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Injury, poisoning and procedural complications
Post procedural haematoma	0/34 (0%)		0/6 (0%)		1/6 (16.7%)		0/1 (0%)
Transfusion reaction	0/34 (0%)		0/6 (0%)		1/6 (16.7%)		0/1 (0%)
Investigations
Blood bilirubin increased	1/34 (2.9%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Blood creatinine increased	2/34 (5.9%)		0/6 (0%)		1/6 (16.7%)		0/1 (0%)
Blood iron increased	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Blood thyroid stimulating hormone increased	3/34 (8.8%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Weight decreased	8/34 (23.5%)		3/6 (50%)		0/6 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Anorexia	9/34 (26.5%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Haemochromatosis	3/34 (8.8%)		0/6 (0%)		1/6 (16.7%)		0/1 (0%)
Hyperglycaemia	2/34 (5.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Hypophosphataemia	2/34 (5.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/34 (2.9%)		1/6 (16.7%)		1/6 (16.7%)		0/1 (0%)
Back pain	2/34 (5.9%)		2/6 (33.3%)		1/6 (16.7%)		1/1 (100%)
Joint swelling	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Muscle spasms	5/34 (14.7%)		0/6 (0%)		2/6 (33.3%)		0/1 (0%)
Myalgia	4/34 (11.8%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Pain in extremity	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Nervous system disorders
Dysgeusia	4/34 (11.8%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Headache	3/34 (8.8%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Psychiatric disorders
Depression	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/34 (5.9%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Dyspnoea exertional	1/34 (2.9%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Pleural effusion	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Pulmonary hypertension	0/34 (0%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Alopecia	4/34 (11.8%)		0/6 (0%)		0/6 (0%)		0/1 (0%)
Skin fissures	1/34 (2.9%)		0/6 (0%)		0/6 (0%)		1/1 (100%)
Vascular disorders
Haematoma	2/34 (5.9%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)
Hypertension	1/34 (2.9%)		1/6 (16.7%)		0/6 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.