Trial Outcomes & Findings for Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer's Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44 (NCT NCT00948766)

Last Updated: 2013-08-28

Results Overview

The ADCS-ADL-SIV is designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a "yes" or "no" question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of "yes" reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

716 participants

Primary outcome timeframe

Baseline of the core study to Week 24 of the core study

Results posted on

2013-08-28

Participant Flow

One patient in each treatment group in the core study and one patient in the treatment group in the extension study did not receive study medication; they were not included in the safety set.

Participant milestones

Participant milestones
Measure	Rivastigmine 13.3 mg/24 h Transdermal Patch Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Rivastigmine 4.6 mg/24 h Transdermal Patch Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).
Core Study STARTED	356	360
Core Study Exposed to Study Medication	355	359
Core Study COMPLETED	229	234
Core Study NOT COMPLETED	127	126
Extension Study STARTED	397	0
Extension Study Exposed to Study Medication	396	0
Extension Study COMPLETED	306	0
Extension Study NOT COMPLETED	91	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Rivastigmine 13.3 mg/24 h Transdermal Patch Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Rivastigmine 4.6 mg/24 h Transdermal Patch Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).
Core Study Adverse Event	73	51
Core Study Unsatisfactory Therapeutic Effect	13	14
Core Study Patient Withdrew Consent	27	46
Core Study Lost to Follow-up	3	2
Core Study Administrative Problems	2	2
Core Study Death	1	1
Core Study Protocol Deviation	8	10
Extension Study Adverse Event	43	0
Extension Study Unsatisfactory Therapeutic Effect	2	0
Extension Study Study Drug No Longer Required	1	0
Extension Study Patient Withdrew Consent	32	0
Extension Study Lost to Follow-up	8	0
Extension Study Administrative Problems	1	0
Extension Study Death	4	0

Baseline Characteristics

Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer's Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch n=356 Participants Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch n=360 Participants Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).	Total n=716 Participants Total of all reporting groups
Age Continuous	77.6 years STANDARD_DEVIATION 8.69 • n=5 Participants	76.5 years STANDARD_DEVIATION 9.35 • n=7 Participants	77.0 years STANDARD_DEVIATION 9.04 • n=5 Participants
Sex: Female, Male Female	227 Participants n=5 Participants	234 Participants n=7 Participants	461 Participants n=5 Participants
Sex: Female, Male Male	129 Participants n=5 Participants	126 Participants n=7 Participants	255 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline of the core study to Week 24 of the core study

Population: Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.

Outcome measures

Outcome measures
Measure	Rivastigmine 13.3 mg/24 h Transdermal Patch n=310 Participants Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Rivastigmine 4.6 mg/24 h Transdermal Patch n=303 Participants Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).
Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24	-2.6 Units on a scale Standard Deviation 6.82	-3.6 Units on a scale Standard Deviation 7.68

PRIMARY outcome

Timeframe: Baseline of the core study to Week 24 of the core study

The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement.

Outcome measures

Outcome measures
Measure	Rivastigmine 13.3 mg/24 h Transdermal Patch n=313 Participants Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Rivastigmine 4.6 mg/24 h Transdermal Patch n=316 Participants Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).
Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24	-1.6 Units on a scale Standard Deviation 13.54	-6.4 Units on a scale Standard Deviation 14.01

SECONDARY outcome

Timeframe: Baseline of the core study to Week 24 of the core study

The ADCS-CGIC assesses the clinical meaningfulness of a treatment based on the clinician's rating of change. The rating is provided by a trained clinician or psychometrician blinded to the patient's treatment. The rater interviewed the patient and caregiver separately at Baseline using a worksheet that provided space for notes and comments. At baseline, raters had access to all of the patient's available records and evaluations. The rater used a similar worksheet at follow-up visits, and referred to the baseline worksheet prior to making a rating of change. The worksheets were divided into 3 domains: mental/cognitive state, behavior, and functioning. Change ratings were based on a 7-point scale: Marked (1), moderate (2), and minimal improvement (3), no change (4), and marked (5), moderate (6), and minimal worsening (7). The percentage of patients in each of the 7 categories is reported.

Outcome measures

Outcome measures
Measure	Rivastigmine 13.3 mg/24 h Transdermal Patch n=313 Participants Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Rivastigmine 4.6 mg/24 h Transdermal Patch n=315 Participants Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).
Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Marked improvement	1.0 Percentage of patients	1.3 Percentage of patients
Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Moderate improvement	3.5 Percentage of patients	3.5 Percentage of patients
Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Minimal improvement	20.1 Percentage of patients	11.4 Percentage of patients
Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 No change	34.2 Percentage of patients	29.2 Percentage of patients
Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Minimal worsening	24.3 Percentage of patients	31.4 Percentage of patients
Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Moderate worsening	14.1 Percentage of patients	19.0 Percentage of patients
Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Marked worsening	2.9 Percentage of patients	4.1 Percentage of patients

SECONDARY outcome

Timeframe: Baseline of the core study to Week 24 of the core study

The NPI-12 assesses a wide range of behaviors encountered in patients with dementia to provide a means of distinguishing the frequency and severity of behavioral changes over time. Ten behavioral and 2 neurovegetative domains were evaluated in an interview with the caregiver given by a mental health professional. The scale included both frequency and severity ratings of each domain as well as a composite domain score (frequency x severity). The sum of the composite scores for the 12 domains yielded the NPI-12 total score. The NPI-12 was scored from 0 to 144, with lower scores reflecting improvement in psychiatric behavior. A negative change score indicates improvement.

Outcome measures

Outcome measures
Measure	Rivastigmine 13.3 mg/24 h Transdermal Patch n=313 Participants Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Rivastigmine 4.6 mg/24 h Transdermal Patch n=313 Participants Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).
Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24	-0.4 Units on a scale Standard Deviation 14.01	1.2 Units on a scale Standard Deviation 16.79

SECONDARY outcome

Timeframe: Baseline of the core study to Week 24 of the extension study

Population: Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.

Outcome measures

Outcome measures
Measure	Rivastigmine 13.3 mg/24 h Transdermal Patch n=372 Participants Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Rivastigmine 4.6 mg/24 h Transdermal Patch Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).
Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24	-4.3 Units on a scale Standard Deviation 8.37	—

SECONDARY outcome

Timeframe: Baseline of the core study to Week 24 of the extension study

Outcome measures

Outcome measures
Measure	Rivastigmine 13.3 mg/24 h Transdermal Patch n=379 Participants Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Rivastigmine 4.6 mg/24 h Transdermal Patch Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).
Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24	-5.9 Units on a scale Standard Deviation 16.72	—

SECONDARY outcome

Timeframe: Baseline of the core study to Week 24 of the extension study

Outcome measures

Outcome measures
Measure	Rivastigmine 13.3 mg/24 h Transdermal Patch n=381 Participants Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Rivastigmine 4.6 mg/24 h Transdermal Patch Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).
Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Marked improvement	1.8 Percentage of patients	—
Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Moderate improvement	5.0 Percentage of patients	—
Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Minimal improvement	9.7 Percentage of patients	—
Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 No change	26.2 Percentage of patients	—
Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Minimal worsening	31.5 Percentage of patients	—
Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Moderate worsening	21.5 Percentage of patients	—
Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 Marked worsening	4.2 Percentage of patients	—

Adverse Events

Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch

Serious events: 82 serious events

Other events: 216 other events

Deaths: 0 deaths

Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch

Serious events: 74 serious events

Other events: 210 other events

Deaths: 0 deaths

Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch

Serious events: 79 serious events

Other events: 248 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch n=355 participants at risk Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).	Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch n=359 participants at risk Patients received rivastigmine 4.6 mg/24 h (5 cm\^2).	Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch n=396 participants at risk Patients received rivastigmine 13.3 mg/24 h (15 cm\^2).
Gastrointestinal disorders Diarrhoea	7.0% 25/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	7.5% 27/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	9.1% 36/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Gastrointestinal disorders Nausea	6.5% 23/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	4.7% 17/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	4.8% 19/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Gastrointestinal disorders Vomiting	7.6% 27/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	6.7% 24/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	7.6% 30/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
General disorders Application site dermatitis	8.5% 30/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	10.0% 36/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	10.9% 43/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
General disorders Application site erythema	13.5% 48/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	12.3% 44/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	13.1% 52/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Infections and infestations Urinary tract infection	11.8% 42/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	12.0% 43/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	14.6% 58/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Injury, poisoning and procedural complications Fall	8.5% 30/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	7.2% 26/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	10.6% 42/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Investigations Weight decreased	10.4% 37/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	7.2% 26/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	11.9% 47/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Psychiatric disorders Agitation	13.2% 47/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	15.3% 55/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	14.6% 58/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Psychiatric disorders Anxiety	5.1% 18/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	5.3% 19/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	4.8% 19/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Psychiatric disorders Depression	5.4% 19/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	4.5% 16/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	4.5% 18/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Psychiatric disorders Hallucination	2.5% 9/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	5.3% 19/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	4.0% 16/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Psychiatric disorders Insomnia	7.6% 27/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	6.7% 24/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	7.6% 30/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Renal and urinary disorders Urinary incontinence	3.7% 13/355 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	3.9% 14/359 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.	5.3% 21/396 • Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks). Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

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 the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER