Efficacy and Tolerability of BAF312 in Patients With Polymyositis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01801917
• Collaborator: (none)
• Enrollment: 14
• Locations: 8
• Arms: 3
• Actual Duration (Months): 39.4
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study assessed the efficacy, safety and tolerability of BAF312 administered orally in patients with clinically active polymyositis and also in patients with polymyositis who had shown inadequate response to corticosteroids and or DMARDs (disease modifying antirheumatic drugs).

Condition or Disease	Intervention/Treatment	Phase
Polymyositis	Drug: Placebo; Drug: BAF312	Phase 2

Detailed Description

This study was stopped prematurely due to overall slow recruitment and no evidence for efficacy in a parallel study in dermatomyositis with an assumed similar pathophysiology. With very small sample sizes per group the overall results for this study including primary and all other efficacy and PD data are inconclusive

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-centre Double-blind, Placebo Controlled, Proof of Concept Study to Evaluate the Efficacy and Tolerability of BAF312 in Patients With Polymyositis
• Actual Study Start Date: Apr 24, 2013
• Actual Primary Completion Date: Aug 5, 2016
• Actual Study Completion Date: Aug 5, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 5 placebo tablets daily during non-titration phase	Drug: Placebo; Matching placebo tablet for oral administration
Experimental: BAF312 2mg 1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during non-titration phase	Drug: BAF312; BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration
Experimental: BAF312 10 mg 5 tablets of BAF312 2 mg daily during non-titration phase	Drug: BAF312; BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration

Outcome Measures

Primary Outcome Measures

1. Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) for Combined Efficacy Endpoint: Manual Muscle Testing in 24 Muscles (MMT24) [Baseline, at 12 weeks]

   Manual Muscle Testing Scoring Sheet: Neck flexors, neck extensors and other designated muscles bilaterally (Biceps brachii, Deltoid middle, Quadriceps, Gluteus maximus, Gluteus medius, Trapezius, Iliopsoas, Hamstrings, Wrist extensors, Wrist Flexors, Ankle plantar flexors and Ankle dorsiflexors) were tested on a 0-10 scale by the Investigator. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The scores range was 0 to 260. Higher scores indicate better outcome.

2. Percent Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) Serum Creatine Kinase (CK) Levels [Baseline, at 12 weeks]

   Serum creatine kinase (CK) were analyzed as part of the blood chemistry panel. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The variable CK was log-transformed for statistical analysis and after estimation was converted to percent change from baseline divided by the mean baseline

Secondary Outcome Measures

1. Six-minute Walking Distance (6MWD) at Week 12 [Baseline, 12 weeks]

   This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted

2. Six-minute Walking Distance (6MWD) at Week 24 [Baseline, 24 weeks]

   This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted

3. BAF312 Trough Plasma Concentrations (PK Set) [-7 Baseline, day 28, 56, 84]

   All blood samples were taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. For each sample, approximately 2 mL of blood was drawn. BAF312 was determined in ethylenediaminetetraacetic acid (EDTA) plasma using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method for the quantification. The anticipated lower limit of quantification (LLOQ) was 0.02 ng/mL using 0.1 mL of plasma

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• "definite" or "probable" for polymyositis at least three months before Baseline

• active disease as defined by elevated CK levels, or other enzymes, or MRI/biopsy if enzymes are normal, and persisting muscle weakness

• stable dose of corticosteroid for at least 2 weeks prior to Baseline and should not have received a medium or high dose in the last 8 weeks prior to study entry.

• patients treated with methotrexate must have been on a stable dose for at least 6 weeks prior to Baseline.

Exclusion Criteria:

• Patients with overlap polymyositis, late-stage polymyositis, or other types of myositis.

• Preexisting severe cardiac or pulmonary involvement, malignancy of any organ system or significant eye diseases.

• Uncontrolled diabetes mellitus or diabetes complicated with organ involvement.

• Pregnant or nursing (lactating) women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Phoenix	Arizona	United States	85013
2	Novartis Investigative Site	Torono	Ontario	Canada	M5G 2C4
3	Novartis Investigative Site	Prague 2		Czechia	128 50
4	Novartis Investigative Site	Budapest		Hungary	1083
5	Novartis Investigative Site	Debrecen		Hungary	4032
6	Novartis Investigative Site	Bydgoszcz		Poland	85-168
7	Novartis Investigative Site	Taichung		Taiwan	40447
8	Novartis Investigative Site	Taichung		Taiwan	40705

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01801917
• Other Study ID Numbers: CBAF312X2205
• First Posted: Mar 1, 2013
• Last Update Posted: Jan 5, 2021
• Last Verified: Jan 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Polymyositis; Myositis; PM; chronic muscle inflammation; inflammatory myopathy; inclusion body myositis
• Additional relevant MeSH terms: Polymyositis; Siponimod

Study Results

Participant Flow

Arm/Group Title	BAF312 2mg/BAF312 2mg	BAF312 10 mg/BAF312 10 mg	Placebo/BAF312 2 mg	Placebo/BAF312 10 mg
Arm/Group Description	Patients in Period 1 continue on same 2 mg dose of BAF312 in Period 2	Patients in Period 1 continue on same 10 mg dose of BAF312 in Period 2	Patients on placebo in Period 1 switch to active 2 mg BAF312 in Period 2	Patients on placebo in Period 1 switch to active 10 mg BAF312 in Period 2
Period Title: Period 1 - Randomized
STARTED	7	2	4	1
COMPLETED	6	2	3	1
NOT COMPLETED	1	0	1	0
Period Title: Period 1 - Randomized
STARTED	6	0	3	0
COMPLETED	6	0	3	0
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	BAF312 2mg/BAF312 2mg	BAF312 10 mg/BAF312 10 mg	Placebo/BAF312 2 mg	Placebo/BAF312 10 mg	Total
Arm/Group Description	Patients in Period 1 continue on same 2 mg dose of BAF312 in Period 2	Patients in Period 1 continue on same 10 mg dose of BAF312 in Period 2	Patients on placebo in Period 1 switch to active 2 mg BAF312 in Period 2	Patients on placebo in Period 1 switch to active 10 mg BAF312 in Period 2	Total of all reporting groups
Overall Participants	7	2	4	1	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.3 (14.78)	47.0 (21.21)	48.0 (8.83)	53.0 (0.0)	49.4 (12.51)
Sex: Female, Male (Count of Participants)
Female	5 71.4%	2 100%	2 50%	1 100%	10 71.4%
Male	2 28.6%	0 0%	2 50%	0 0%	4 28.6%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	7 100%	1 50%	3 75%	0 0%	11 78.6%
Black	0 0%	0 0%	0 0%	1 100%	1 7.1%
Asian	0 0%	1 50%	1 25%	0 0%	2 14.3%
Disease duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.6 (4.46)	5.4 (2.74)	2.7 (1.67)	16.9 (0)	5.6 (4.77)
Baseline MMT24 Score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	202.6 (41.74)	184.0 (19.80)	189.5 (45.65)	166.0 (0)	193.6 (37.90)
Taking DMARD at baseline (participants) [Number]
Number [participants]	7 100%	2 100%	4 100%	1 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) for Combined Efficacy Endpoint: Manual Muscle Testing in 24 Muscles (MMT24)
Description	Manual Muscle Testing Scoring Sheet: Neck flexors, neck extensors and other designated muscles bilaterally (Biceps brachii, Deltoid middle, Quadriceps, Gluteus maximus, Gluteus medius, Trapezius, Iliopsoas, Hamstrings, Wrist extensors, Wrist Flexors, Ankle plantar flexors and Ankle dorsiflexors) were tested on a 0-10 scale by the Investigator. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The scores range was 0 to 260. Higher scores indicate better outcome.
Time Frame	Baseline, at 12 weeks

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) included patients with PD data and no major protocol deviations

Arm/Group Title	BAF312 2mg	BAF312 10 mg	Placebo
Arm/Group Description	1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1	5 tablets of BAF312 2 mg daily during Period 1	matching placebo
Measure Participants	7	2	5
Mean (90% Confidence Interval) [scores on a scale]	11.2	39.0	9.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BAF312 2mg, Placebo
	Comments	It was a Bayesian analysis with non-informative prior for co-primary endpoints, MMT-24 and CK, with dual criteria for statistical significance: ≥ 90% posterior probability (PP) of achieving an increase from baseline in MMT24 and decrease in CK and clinical relevance: ≥ 50% PP achieving an increase of 15 points in MMT24 and a decrease of 30% in CK vs. placebo. For this table the value is the posterior probability of achieving an increase in MMT24 and a decrease in CK in 2mg group vs. placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Bayesian
	Estimated Value	0.586
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BAF312 2mg, Placebo
	Comments	It was a Bayesian analysis with non-informative prior for co-primary endpoints, MMT-24 and CK, with dual criteria for statistical significance: ≥ 90% posterior probability (PP) of achieving an increase from baseline in MMT24 and decrease in CK and clinical relevance: ≥ 50% PP achieving an increase of 15 points in MMT24 and a decrease of 30% in CK vs. placebo. . For this table the value is the PP of achieving an increase of 15 points in MMT24 and a decrease of 30% in CK in 2mg group vs. placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Bayesian
	Estimated Value	0.022
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BAF312 10 mg, Placebo
	Comments	It was a Bayesian analysis with non-informative prior for co-primary endpoints, MMT-24 and CK, with dual criteria for statistical significance: ≥ 90% posterior probability (PP) of achieving an increase from baseline in MMT24 and decrease in CK and clinical relevance: ≥ 50% PP achieving an increase of 15 points in MMT24 and a decrease of 30% in CK vs. placebo. For this table the value is the posterior probability of achieving an increase in MMT24 and a decrease in CK in 10mg group vs. placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Bayesian
	Estimated Value	0.963
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BAF312 10 mg, Placebo
	Comments	It was a Bayesian analysis with non-informative prior for co-primary endpoints, MMT-24 and CK, with dual criteria for statistical significance: ≥ 90% posterior probability (PP) of achieving an increase from baseline in MMT24 and decrease in CK and clinical relevance: ≥ 50% PP achieving an increase of 15 points in MMT24 and a decrease of 30% in CK vs. placebo. . For this table the value is the PP of achieving an increase of 15 points in MMT24 and a decrease of 30% in CK in 10mg group vs. placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Bayesian
	Estimated Value	0.837
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percent Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) Serum Creatine Kinase (CK) Levels
Description	Serum creatine kinase (CK) were analyzed as part of the blood chemistry panel. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The variable CK was log-transformed for statistical analysis and after estimation was converted to percent change from baseline divided by the mean baseline
Time Frame	Baseline, at 12 weeks

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) included patients with PD data and no major protocol deviations

Arm/Group Title	BAF312 2mg	BAF312 10 mg	Placebo
Arm/Group Description	1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1	5 tablets of BAF312 2 mg daily during Period 1	matching placebo
Measure Participants	7	2	5
Mean (90% Confidence Interval) [U/L]	-19.7	-55.6	-0.5

3. Secondary Outcome

Title	Six-minute Walking Distance (6MWD) at Week 12
Description	This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) included patients with PD data and no major protocol deviations

Arm/Group Title	BAF312 2mg	BAF312 10 mg	Placebo
Arm/Group Description	1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1	5 tablets of BAF312 2 mg daily during Period 1	matching placebo
Measure Participants	6	1	4
Period 1, Week 12	362.47 (52.02)	393.00 (0.0)	303.10 (112.480)
Distance walked,change from BL at Wk 12	46.82 (65.64)	23.00 (0.0)	-6.40 (21.981)

4. Secondary Outcome

Title	Six-minute Walking Distance (6MWD) at Week 24
Description	This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) included patients with PD data and no major protocol deviations

Arm/Group Title	BAF312 2mg	Placebo/BAF312 2 mg
Arm/Group Description	1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1	Patients on placebo in Period 1 switch to active 2 mg BAF312 in Period 2
Measure Participants	6	3
Period 2, Week 24	364.60 (73.803)	329.33 (186.551)
Distance walked,change from baseline at Wk 24	48.95 (91.922)	4.33 (51.637)

5. Secondary Outcome

Title	BAF312 Trough Plasma Concentrations (PK Set)
Description	All blood samples were taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. For each sample, approximately 2 mL of blood was drawn. BAF312 was determined in ethylenediaminetetraacetic acid (EDTA) plasma using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method for the quantification. The anticipated lower limit of quantification (LLOQ) was 0.02 ng/mL using 0.1 mL of plasma
Time Frame	-7 Baseline, day 28, 56, 84

Outcome Measure Data

Analysis Population Description

P

Arm/Group Title	BAF312 2mg	BAF312 10 mg
Arm/Group Description	1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during Period 1	5 tablets of BAF312 2 mg daily during Period 1
Measure Participants	6	2
Day - 7	0 (0)	0 (0)
Day 28	25.3 (11.2)	182 (0)
Day 56	25.1 (12.6)	270 (0)
Day 84	21.4 (10.1)	240 (0)

Adverse Events

Time Frame	Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Arm/Group Title	Period 1 BAF312 2mg		Period 1 BAF312 10mg		Period 1 Placebo		Period 2 BAF312 2mg/ BAF312 2mg		Period 2 Placebo/ BAF312 2mg
Arm/Group Description	Period 1 BAF312 2mg		Period 1 BAF312 10mg		Period 1 Placebo		Period 2 BAF312 2mg/ BAF312 2mg		Period 2 Placebo/ BAF312 2mg
All Cause Mortality
	Period 1 BAF312 2mg		Period 1 BAF312 10mg		Period 1 Placebo		Period 2 BAF312 2mg/ BAF312 2mg		Period 2 Placebo/ BAF312 2mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Period 1 BAF312 2mg		Period 1 BAF312 10mg		Period 1 Placebo		Period 2 BAF312 2mg/ BAF312 2mg		Period 2 Placebo/ BAF312 2mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Blood and lymphatic system disorders
Haemolytic anaemia	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Haemolytic uraemic syndrome	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Renal and urinary disorders
Acute kidney injury	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Period 1 BAF312 2mg		Period 1 BAF312 10mg		Period 1 Placebo		Period 2 BAF312 2mg/ BAF312 2mg		Period 2 Placebo/ BAF312 2mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/7 (85.7%)		2/2 (100%)		4/5 (80%)		4/6 (66.7%)		2/3 (66.7%)
Cardiac disorders
Palpitations	0/7 (0%)		0/2 (0%)		1/5 (20%)		0/6 (0%)		0/3 (0%)
Eye disorders
Cataract	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		1/3 (33.3%)
Eye pain	0/7 (0%)		1/2 (50%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Ocular hyperaemia	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Vitreous detachment	0/7 (0%)		0/2 (0%)		0/5 (0%)		1/6 (16.7%)		0/3 (0%)
Gastrointestinal disorders
Abdominal pain upper	1/7 (14.3%)		0/2 (0%)		1/5 (20%)		0/6 (0%)		0/3 (0%)
Diarrhoea	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		1/3 (33.3%)
Nausea	1/7 (14.3%)		0/2 (0%)		1/5 (20%)		0/6 (0%)		0/3 (0%)
Vomiting	0/7 (0%)		1/2 (50%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
General disorders
Asthenia	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Chest discomfort	0/7 (0%)		1/2 (50%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Fatigue	0/7 (0%)		0/2 (0%)		1/5 (20%)		1/6 (16.7%)		0/3 (0%)
Feeling cold	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Pyrexia	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Hepatobiliary disorders
Cholelithiasis	0/7 (0%)		0/2 (0%)		0/5 (0%)		1/6 (16.7%)		0/3 (0%)
Infections and infestations
Nasopharyngitis	0/7 (0%)		0/2 (0%)		1/5 (20%)		0/6 (0%)		0/3 (0%)
Upper respiratory tract infection	0/7 (0%)		0/2 (0%)		0/5 (0%)		1/6 (16.7%)		1/3 (33.3%)
Urinary tract infection	0/7 (0%)		1/2 (50%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Injury, poisoning and procedural complications
Epicondylitis	0/7 (0%)		0/2 (0%)		1/5 (20%)		0/6 (0%)		0/3 (0%)
Investigations
Carbon monoxide diffusing capacity decreased	0/7 (0%)		0/2 (0%)		1/5 (20%)		0/6 (0%)		0/3 (0%)
Cardiac murmur	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Gamma-glutamyltransferase increased	0/7 (0%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Musculoskeletal pain	0/7 (0%)		0/2 (0%)		0/5 (0%)		1/6 (16.7%)		0/3 (0%)
Myalgia	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Pain in extremity	0/7 (0%)		0/2 (0%)		0/5 (0%)		1/6 (16.7%)		0/3 (0%)
Polymyositis	0/7 (0%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		1/3 (33.3%)
Spinal pain	0/7 (0%)		0/2 (0%)		0/5 (0%)		1/6 (16.7%)		0/3 (0%)
Nervous system disorders
Cerebral artery stenosis	0/7 (0%)		0/2 (0%)		1/5 (20%)		0/6 (0%)		0/3 (0%)
Dizziness	0/7 (0%)		1/2 (50%)		2/5 (40%)		0/6 (0%)		0/3 (0%)
Headache	2/7 (28.6%)		0/2 (0%)		2/5 (40%)		0/6 (0%)		0/3 (0%)
Psychiatric disorders
Depression	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	1/7 (14.3%)		0/2 (0%)		0/5 (0%)		0/6 (0%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Papule	0/7 (0%)		0/2 (0%)		0/5 (0%)		1/6 (16.7%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. 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.