MACS1428: CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01227577
• Collaborator: (none)
• Enrollment: 128
• Locations: 32
• Arm: 1
• Duration (Months): 48
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

"This is a single-arm, open-label, multi-center study of complete molecular response (CMR) in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP). The study is designed to evaluate early and deep molecular responses up to 4 years on nilotinib treatment. The primary end point is Rate of confirmed CMR in newly diagnosed Philadelphia chromosome positive CML-CP patients."

Condition or Disease	Intervention/Treatment	Phase
Chronic Myelogenous Leukemia in Chronic Phase	Drug: Nilotinib	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-arm, Open-label, Multi-center Study of Complete Molecular Response (CMR) in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nilotinib Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.	Drug: Nilotinib; Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Confirmed Complete Molecular Response (CMR) [4 years]

   CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl <=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.

Secondary Outcome Measures

1. Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR) [4 years]

   CCyR was defined as 0% Philadelphia chromosome-positive (Ph+) metaphases in the bone marrow. MMR was defined as a 3 log reduction of Bcr-Abl transcripts from the standardized baseline on the international scale (equivalent to Bcr-Abl ≤ 0.1% IS). Bcr-Abl transcripts assessed by peripheral blood quatitative real time polymerase chain reaction (RQ-PCR) were used for the determination of all molecular responses.

2. Time to CMR, CCyR and MMR [4 years]

   Time to CMR, CCyR, and MMR was defined as the time from the date of enrollment to the date of first documented CMR, CCyR and MMR, respectively.

3. Duration of CMR, CCyR and MMR [4 years]

   Duration of CMR, CCyR and MMR were defined as the time from the first date of achievement of the response to the date of first documented loss of the response.

4. Number of Participants With Progression to Accelerated Phase/Blastic Crisis (AP/BC) [4 years]

   Progression to AP/BC is defined as loss of CCyR, MMR, and CMR and was summarized by frequencies and percentages.

5. Time to Progression of AP/BC [4 years]

   Time to progression of AP/BC was defined as the time from the date of the first dose of study drug to the date of first documented progression of AP/BC.

6. Number of Participants With Loss of CCyR, MMR and CMR [4 years]

   Rate of loss of CMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.0032% IS. Rate of loss of CCyR was defined as an increase in the Ph+ bone marrow cells to greater than 0%. Rate of loss of MMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.1% IS.

7. Number of Participants With CMR Who Were Dosed to 400 mg b.i.d. [4 years]

   CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl <=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.

8. Event-free Survival, Progression-free Survival and Overall Survival [4 years]

   Event-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: loss of Complete Hematological Response (CHR), loss of CCyR, loss of Partial Cytogenetic Response (PCyR), progression to the accelerated phase or blast crisis, and death from any cause. Progression-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: progression to the accelerated phase or blast crisis, death, and loss of CMR. Overall survival was defined as the time from the date of enrollment until death due to any cause.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Patients with Ph+ CML-CP within 3 months of diagnosis. Male or female patients' ≥ 18 years of age. Patients must have adequate end organ function.

Exclusion Criteria:

Previously documented T315I mutation. Other CML treatment is an exclusion criteria with the following exception: While awaiting study start, patients may be treated with anagrelide (no treatment duration limit), hydroxyurea (no treatment duration limit), and/or up to a 14 day supply of a tyrosine kinase inhibitor (TKI) approved by the FDA for frontline treatment. Patients taking a TKI prior to study entry must have at least a one day washout from their last dose of medication and have recovered from any side effects of such therapy.

Impaired cardiac function as defined by the protocol. Patients with contraindications to receiving nilotinib, including concomitant medications.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Cancer Medical Center, Inc.	Anaheim	California	United States	92801
2	Providence St. Joseph Medical Center Roy&Patricia Disney Fam Cancer	Burbank	California	United States	91505-6866
3	Bay Area Cancer Research Dept.ofBayAreaCancerResearch	Concord	California	United States	94520
4	St. Jude Heritage Medical Group Virginia Crosson Cancer Center	Yorba Linda	California	United States	92886
5	Sarah Cannon Research Institute SCRI	Jacksonville	Florida	United States	32256
6	Advanced Medical Specialties	Miami	Florida	United States	33176
7	Pasco Hernando Oncology	New Port Richey	Florida	United States	34652
8	Georgia Regents University MedCollege of GA Cancer Ctr 2	Augusta	Georgia	United States	30912
9	Stroger Cook County Hospital Division of Hematology & Onc	Chicago	Illinois	United States	60612
10	Louis A. Weiss Memorial Hospital	Chicago	Illinois	United States	60640
11	Indiana Blood and Marrow Institute	Beach Grove	Indiana	United States	46107
12	Cancer Center of Kansas	Witchita	Kansas	United States	67214-3728
13	LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center(3)	New Orleans	Louisiana	United States	70115
14	University of Maryland	Baltimore	Maryland	United States	21201
15	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
16	Henry Ford Hospital	Detroit	Michigan	United States	48202
17	St. Louis University Cancer Center	St. Louis	Missouri	United States	63110
18	University of Nebraska Medical Center University of Nebraska Med Ctr	Omaha	Nebraska	United States	68198
19	Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.	Hackensack	New Jersey	United States	07601
20	Montefiore Medical Center	Bronx	New York	United States	10467
21	University of Rochester Medical Ct James P Wilmot Cancer Ctr	Rochester	New York	United States	14642
22	Duke University Medical Center Duke University Med Ctr	Durham	North Carolina	United States	27710
23	Oregon Health & Science University	Portland	Oregon	United States	97201
24	Cancer Centers of the Carolinas Cancer Center	Greenville	South Carolina	United States	29605
25	Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology	Chattanooga	Tennessee	United States	37404
26	The Jones Clinic	Germantown	Tennessee	United States	38138
27	Tennessee Oncology Sarah Cannon Research Inst.	Nashville	Tennessee	United States	37203
28	Baylor Research Institute Baylor Research Institute (17)	Dallas	Texas	United States	75204
29	Oncology Consultants Oncology Consultants, P.A.	Houston	Texas	United States	77024
30	Millennium Oncology	Houston	Texas	United States	77090
31	University of Virginia	Charlottesville	Virginia	United States	22908
32	Providence Regional Cancer Partnership	Everett	Washington	United States	98201

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: NCT01227577
• Other Study ID Numbers: CAMN107AUS28
• First Posted: Oct 25, 2010
• Last Update Posted: Feb 8, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by Novartis Pharmaceuticals: CML; Chronic Myelogenous Leukemia; Leukemia; CML-CP; Nilotinib
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Results

Participant Flow

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Period Title: Overall Study
STARTED	128
COMPLETED	93
NOT COMPLETED	35

Baseline Characteristics

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Overall Participants	128
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.6 (14.99)
Sex: Female, Male (Count of Participants)
Female	64 50%
Male	64 50%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Confirmed Complete Molecular Response (CMR)
Description	CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl <=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study drug.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Measure Participants	128
Number [Participants]	34 26.6%

2. Secondary Outcome

Title	Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR)
Description	CCyR was defined as 0% Philadelphia chromosome-positive (Ph+) metaphases in the bone marrow. MMR was defined as a 3 log reduction of Bcr-Abl transcripts from the standardized baseline on the international scale (equivalent to Bcr-Abl ≤ 0.1% IS). Bcr-Abl transcripts assessed by peripheral blood quatitative real time polymerase chain reaction (RQ-PCR) were used for the determination of all molecular responses.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study drug.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Measure Participants	128
CCyR	93 72.7%
MMR	94 73.4%

3. Secondary Outcome

Title	Time to CMR, CCyR and MMR
Description	Time to CMR, CCyR, and MMR was defined as the time from the date of enrollment to the date of first documented CMR, CCyR and MMR, respectively.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Of the 128 participants analyzed, 34 participants achieved CMR within 18 months of treatment, 93 participants achieved CCyR and did not experience loss of CCyR during the study, and 94 participants achieved MMR with up to 24 months of treatment (most achieved MMR within 12 months of treatment).

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Measure Participants	128
CMR (n=34)	NA
CCyR (n=93)	5.5
MMR (n=94)	5.7

4. Secondary Outcome

Title	Duration of CMR, CCyR and MMR
Description	Duration of CMR, CCyR and MMR were defined as the time from the first date of achievement of the response to the date of first documented loss of the response.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Of the 128 participants analyzed, 34 participants achieved CMR within 18 months of treatment, 93 participants achieved CCyR and did not experience loss of CCyR during the study, and 94 participants achieved MMR with up to 24 months of treatment (most achieved MMR within 12 months of treatment).

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Measure Participants	128
CMR (n=34)	7.97 (3.705)
CCyR (n=93)	NA (NA)
MMR (n=94)	4.86 (5.003)

5. Secondary Outcome

Title	Number of Participants With Progression to Accelerated Phase/Blastic Crisis (AP/BC)
Description	Progression to AP/BC is defined as loss of CCyR, MMR, and CMR and was summarized by frequencies and percentages.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study drug.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Measure Participants	128
Number [Participants]	1 0.8%

6. Secondary Outcome

Title	Time to Progression of AP/BC
Description	Time to progression of AP/BC was defined as the time from the date of the first dose of study drug to the date of first documented progression of AP/BC.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Of the 128 participants analyzed, 1 participant experienced progression to AP/BC.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Measure Participants	128
Median (95% Confidence Interval) [Months]	NA

7. Secondary Outcome

Title	Number of Participants With Loss of CCyR, MMR and CMR
Description	Rate of loss of CMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.0032% IS. Rate of loss of CCyR was defined as an increase in the Ph+ bone marrow cells to greater than 0%. Rate of loss of MMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.1% IS.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Numbers are based on the total number of participants who achieved and experienced loss of CMR (34 participants), CCyr (93 participants) and MMR (94 participants), respectively.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Measure Participants	128
CMR (n=34)	6 4.7%
CCyR (n=93)	0 0%
MMR (n=94)	13 10.2%

8. Secondary Outcome

Title	Number of Participants With CMR Who Were Dosed to 400 mg b.i.d.
Description	CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl <=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Of the 128 participants analyzed, 3 participants received an escalated dose of 400 mg b.i.d.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Measure Participants	3
Number [Participants]	0 0%

9. Secondary Outcome

Title	Event-free Survival, Progression-free Survival and Overall Survival
Description	Event-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: loss of Complete Hematological Response (CHR), loss of CCyR, loss of Partial Cytogenetic Response (PCyR), progression to the accelerated phase or blast crisis, and death from any cause. Progression-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: progression to the accelerated phase or blast crisis, death, and loss of CMR. Overall survival was defined as the time from the date of enrollment until death due to any cause.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study drug.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Measure Participants	128
Event-free	NA
Progression-free	NA
Overall	NA

Adverse Events

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
All Cause Mortality
	Nilotinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nilotinib
	Affected / at Risk (%)	# Events
Total	27/128 (21.1%)
Blood and lymphatic system disorders
Neutropenia	2/128 (1.6%)
Thrombocytopenia	2/128 (1.6%)
Cardiac disorders
Atrial fibrillation	1/128 (0.8%)
Myocardial infarction	3/128 (2.3%)
Palpitations	1/128 (0.8%)
Endocrine disorders
Hyperthyroidism	1/128 (0.8%)
Toxic nodular goitre	1/128 (0.8%)
Gastrointestinal disorders
Abdominal pain	4/128 (3.1%)
Gastritis	1/128 (0.8%)
Intestinal obstruction	1/128 (0.8%)
Nausea	1/128 (0.8%)
Oesophagitis	1/128 (0.8%)
Pancreatitis	3/128 (2.3%)
Small intestinal obstruction	1/128 (0.8%)
Vomiting	1/128 (0.8%)
General disorders
Chest pain	2/128 (1.6%)
Pyrexia	1/128 (0.8%)
Hepatobiliary disorders
Cholecystitis acute	1/128 (0.8%)
Infections and infestations
Device related infection	1/128 (0.8%)
Gastroenteritis	1/128 (0.8%)
Gastroenteritis viral	1/128 (0.8%)
Pharyngitis streptococcal	1/128 (0.8%)
Pneumonia	3/128 (2.3%)
Sepsis	1/128 (0.8%)
Upper respiratory tract infection	1/128 (0.8%)
Injury, poisoning and procedural complications
Fall	1/128 (0.8%)
Metabolism and nutrition disorders
Hyponatraemia	1/128 (0.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/128 (0.8%)
Flank pain	1/128 (0.8%)
Musculoskeletal chest pain	1/128 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anaplastic astrocytoma	1/128 (0.8%)
Nervous system disorders
Central nervous system lesion	1/128 (0.8%)
Cerebrovascular accident	1/128 (0.8%)
Hypoaesthesia	1/128 (0.8%)
Migraine	1/128 (0.8%)
Neurological symptom	1/128 (0.8%)
Sciatica	1/128 (0.8%)
Syncope	1/128 (0.8%)
Transient ischaemic attack	1/128 (0.8%)
Psychiatric disorders
Depression	1/128 (0.8%)
Mental status changes	1/128 (0.8%)
Renal and urinary disorders
Renal failure acute	1/128 (0.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/128 (0.8%)
Hiccups	1/128 (0.8%)
Hypoxia	1/128 (0.8%)
Pleural effusion	1/128 (0.8%)
Surgical and medical procedures
Thyroidectomy	1/128 (0.8%)
Other (Not Including Serious) Adverse Events
	Nilotinib
	Affected / at Risk (%)	# Events
Total	122/128 (95.3%)
Blood and lymphatic system disorders
Anaemia	22/128 (17.2%)
Leukopenia	7/128 (5.5%)
Neutropenia	13/128 (10.2%)
Thrombocytopenia	18/128 (14.1%)
Cardiac disorders
Palpitations	8/128 (6.3%)
Gastrointestinal disorders
Abdominal distension	7/128 (5.5%)
Abdominal pain	24/128 (18.8%)
Abdominal pain upper	12/128 (9.4%)
Constipation	30/128 (23.4%)
Diarrhoea	29/128 (22.7%)
Dry mouth	13/128 (10.2%)
Dyspepsia	10/128 (7.8%)
Gastrooesophageal reflux disease	7/128 (5.5%)
Nausea	45/128 (35.2%)
Vomiting	23/128 (18%)
General disorders
Asthenia	7/128 (5.5%)
Chest pain	8/128 (6.3%)
Fatigue	58/128 (45.3%)
Oedema peripheral	9/128 (7%)
Pyrexia	8/128 (6.3%)
Hepatobiliary disorders
Hyperbilirubinaemia	9/128 (7%)
Infections and infestations
Bronchitis	8/128 (6.3%)
Sinusitis	9/128 (7%)
Upper respiratory tract infection	21/128 (16.4%)
Urinary tract infection	8/128 (6.3%)
Investigations
Alanine aminotransferase increased	19/128 (14.8%)
Amylase increased	10/128 (7.8%)
Aspartate aminotransferase increased	11/128 (8.6%)
Blood bilirubin increased	17/128 (13.3%)
Lipase increased	31/128 (24.2%)
Weight increased	8/128 (6.3%)
White blood cell count decreased	7/128 (5.5%)
Metabolism and nutrition disorders
Decreased appetite	17/128 (13.3%)
Hyperglycaemia	9/128 (7%)
Hypomagnesaemia	8/128 (6.3%)
Hypophosphataemia	8/128 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	25/128 (19.5%)
Back pain	10/128 (7.8%)
Bone pain	9/128 (7%)
Muscle spasms	22/128 (17.2%)
Myalgia	23/128 (18%)
Pain in extremity	12/128 (9.4%)
Nervous system disorders
Dizziness	23/128 (18%)
Headache	31/128 (24.2%)
Hypoaesthesia	14/128 (10.9%)
Paraesthesia	9/128 (7%)
Somnolence	8/128 (6.3%)
Psychiatric disorders
Anxiety	12/128 (9.4%)
Depression	10/128 (7.8%)
Insomnia	15/128 (11.7%)
Respiratory, thoracic and mediastinal disorders
Cough	15/128 (11.7%)
Dyspnoea	26/128 (20.3%)
Oropharyngeal pain	12/128 (9.4%)
Skin and subcutaneous tissue disorders
Alopecia	22/128 (17.2%)
Dry skin	18/128 (14.1%)
Night sweats	9/128 (7%)
Pruritus	20/128 (15.6%)
Rash	48/128 (37.5%)

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.