Study of Efficacy and Safety of VAY736 in Patients With Pemphigus Vulgaris

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01930175
• Collaborator: (none)
• Enrollment: 13
• Locations: 5
• Arms: 3
• Actual Duration (Months): 69.2
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The study evaluated the efficacy, safety and pharmacokinetics of VAY736 in the treatment of patients with pemphigus vulagaris (PV).

Condition or Disease	Intervention/Treatment	Phase
Pemphigus Vulgaris	Drug: VAY736; Drug: Placebo	Phase 2

Detailed Description

This was a non-confirmatory, randomized, partial-blind, placebo-controlled trial evaluating the efficacy, safety and pharmacokinetics (PK) of VAY736 in the treatment of PV patients.

A total of 13 patients were enrolled and randomized into the study. Of these 13 patients,seven were randomized to the 3 mg/kg VAY736 group, two were randomized to the 10 mg/kg VAY736 group and four were randomized to the placebo group.In the placebo group, three out of the four patients consented to open-label VAY736 treatment and received 10 mg/kg VAY736 after Week 24 onwards. Thus, a total of 12 patients received VAY736, 7 patients received 3 mg/kg and 5 patients 10 mg/kg.

The Screening period consisted of a Screening Visit performed within 28 days prior to randomization to assess patient eligibility. Following Screening, patients underwent pre-dose procedures which included assessment of their PV by Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin disease Intensity Score (ABSIS) and Investigator Global Assessment (IGA), and blood sampling for PK endpoints. Patients then received the study drug, which was administered over approximately a 2 hour period. The patients remained in the study center overnight post-infusion for observation and for measurement of safety parameters and PK samples approximately 24 h post-infusion (start of infusion: ±2 h). Patients were then discharged from the study site and returned as per the schedule. Patients were evaluated at Week 1, Week 2 and Week 3, then every 3 weeks through to Week 12, and every 4 weeks through to Week 24. At Week 24, the blind was broken to confirm treatment allocation. If a patient was on placebo, such patient completing the Week 24 visit and after unblinding had the option of receiving open label VAY736 10mg/kg.

Recruitment was paused in Mar-2015 and at the time 13 patients were enrolled. The study recruitment was then terminated in Dec-2015 for strategic reasons related to the development of the compound.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Partial-blind, Placebo-controlled Trial Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of VAY736 in the Treatment of Patients With Pemphigus Vulgaris
• Actual Study Start Date: Dec 18, 2013
• Actual Primary Completion Date: Sep 25, 2019
• Actual Study Completion Date: Sep 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo single dose iv of Placebo	Drug: Placebo
Experimental: VAY736 3 mg/kg single dose iv of VAY736 at a dose of 3mg/kg	Drug: VAY736; Other Names: Ianalumab
Experimental: VAY736 10 mg/kg single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo.	Drug: VAY736; Other Names: Ianalumab

Outcome Measures

Primary Outcome Measures

1. Pemphigus Disease Area Index (PDAI) at Week 12 [Week 12]

   PDAI is specific cutaneous and mucosal disease activity assessment performed by investigator based on evaluation of lesions in well-defined anatomical locations. The score weighted for the number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Damage, such as post inflammatory hyperpigmentation or erythema from resolving lesion, scored separately from the main score as absent (0) or present (1) for each body area or scalp resulting in a score of 0 to 12 or 0 to 1, respectively. Thus, PDAI ranged from 0 to 263, with 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity) and 13 points representing disease damage.

Secondary Outcome Measures

1. Autoimmune Skin Disease Intensity Score (ABSIS) at Baseline and Week 12. [Baseline, Week 12]

   The ABSIS Score is a quality- and quantity-based score for cutaneous and oral mucosal lesions combining the extent of the affected body surface area (BSA), the quality of the skin lesions and oral involvement. The ABSIS score ranged from 0 to 206 with 150 points for skin involvement, 11 points for oral involvement and 45 points for subjective discomfort during eating and drinking. A reduction from baseline (or, a negative change from baseline) in ABSIS indicates improvement in patients.

2. Change From Baseline in Investigator Global Assessment (IGA) at Week 12 [Baseline, Week 12]

   The IGA score ranges from 0 to 4 and the decrease or reduction from baseline in IGA score indicates improvement in patients. IGA score scale: 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe active disease

3. VAY736 Serum Concentration - AUCinf [predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks]

   The area under the serum concentration-time curve from time zero to infinity [mass × time / volume]. The concentration of VAY736 was measured in the serum.

4. VAY736 Serum Concentration - AUClast [predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks]

   The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration [mass × time / volume]. The concentration of VAY736 was measured in the serum.

5. VAY736 Serum Concentration - Cmax [predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks]

   The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum.

6. VAY736 Serum Concentration - Tmax [predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks]

   Tmax is the time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum.

7. VAY736 Serum Concentration - T1/2 [predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks]

   T1/2 is the terminal elimination half-life [time]. The concentration of VAY736 was measured in the serum.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients 20 to 70 years of age

• Confirmed diagnosis of pemphigus vulgaris

• Presence of mild to moderate pemphigus vulgaris

• Patients must weight between 40 kg and 150 kg inclusive

• on a stable dose of oral corticosteriod therapy (with or without azathioprine or mycophenolate)

Exclusion Criteria:

• Pregnant or nursing (lactating) women

• Women of child-bearing potential unless they are using a highly effective method of birth control during dosing and for 4 months following study treatment

• Recent previous treatment with photo therapy, biological therapy, steroids, immunosuppresive agents (unless washout period applied)

• Active or recent history of clinically significant infection

• use of rituximab within 1 year Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Chapel Hill	North Carolina	United States	27516
2	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19104
3	Novartis Investigative Site	Vienna		Austria	1040
4	Novartis Investigative Site	Sofia	BGR	Bulgaria	1431
5	Novartis Investigative Site	Taipei		Taiwan	10002

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Apr 9, 2019
• Statistical Analysis Plan - Jul 13, 2017

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01930175
• Other Study ID Numbers: CVAY736X2203
• First Posted: Aug 28, 2013
• Last Update Posted: Oct 8, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Pemphigus vulgaris; pemphigus; blistering disease
• Additional relevant MeSH terms: Pemphigus

Study Results

Participant Flow

Recruitment Details	A total of 13 participants were enrolled and randomized into the study from Austria (1 center); Bulgaria (1 center); Taiwan (1 center); USA (2 centers).
Pre-assignment Detail	The study was planned to be conducted in approximately 32 patients. However, after enrolling 13 patients, the recruitment was terminated due to strategic reasons related to the development of the compound.

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo
Period Title: Core Study
STARTED	7	2	4
Safety Analysis Set	7	2	4
Pharmacokinetics (PK) Analysis Set	7	2	0
COMPLETED	7	1	3
NOT COMPLETED	0	1	1
Period Title: Core Study
STARTED	0	0	3
COMPLETED	0	0	3
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo	Total
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo	Total of all reporting groups
Overall Participants	7	2	4	13
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.6 (10.45)	35.0 (8.49)	56.0 (8.83)	50.4 (11.44)
Sex: Female, Male (Count of Participants)
Female	3 42.9%	0 0%	2 50%	5 38.5%
Male	4 57.1%	2 100%	2 50%	8 61.5%
Race/Ethnicity, Customized (Count of Participants)
Asian	2 28.6%	1 50%	1 25%	4 30.8%
Caucasian	4 57.1%	1 50%	3 75%	8 61.5%
Other	1 14.3%	0 0%	0 0%	1 7.7%

Outcome Measures

1. Primary Outcome

Title	Pemphigus Disease Area Index (PDAI) at Week 12
Description	PDAI is specific cutaneous and mucosal disease activity assessment performed by investigator based on evaluation of lesions in well-defined anatomical locations. The score weighted for the number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Damage, such as post inflammatory hyperpigmentation or erythema from resolving lesion, scored separately from the main score as absent (0) or present (1) for each body area or scalp resulting in a score of 0 to 12 or 0 to 1, respectively. Thus, PDAI ranged from 0 to 263, with 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity) and 13 points representing disease damage.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All evaluable patients.

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo
Measure Participants	7	2	3
Mean (Standard Deviation) [Score on the scale]	5.90 (1.836)	10.15 (8.273)	22.07 (25.628)

2. Secondary Outcome

Title	Autoimmune Skin Disease Intensity Score (ABSIS) at Baseline and Week 12.
Description	The ABSIS Score is a quality- and quantity-based score for cutaneous and oral mucosal lesions combining the extent of the affected body surface area (BSA), the quality of the skin lesions and oral involvement. The ABSIS score ranged from 0 to 206 with 150 points for skin involvement, 11 points for oral involvement and 45 points for subjective discomfort during eating and drinking. A reduction from baseline (or, a negative change from baseline) in ABSIS indicates improvement in patients.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All evaluable patients.

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo
Measure Participants	7	2	4
Baseline	13.26 (7.621)	16.38 (12.905)	33.75 (21.620)
Week 12	2.19 (3.465)	5.55 (7.707)	16.17 (25.838)

3. Secondary Outcome

Title	Change From Baseline in Investigator Global Assessment (IGA) at Week 12
Description	The IGA score ranges from 0 to 4 and the decrease or reduction from baseline in IGA score indicates improvement in patients. IGA score scale: 0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe active disease
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All evaluable patients.

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo
Measure Participants	7	2	3
Mean (Standard Deviation) [Score on the scale]	-1.4 (0.79)	-1.0 (0.00)	-0.7 (0.58)

4. Secondary Outcome

Title	VAY736 Serum Concentration - AUCinf
Description	The area under the serum concentration-time curve from time zero to infinity [mass × time / volume]. The concentration of VAY736 was measured in the serum.
Time Frame	predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Outcome Measure Data

Analysis Population Description

PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo
Measure Participants	7	2	0
Mean (Standard Deviation) [day*ug/mL]	440 (114)	1480 (231)

5. Secondary Outcome

Title	VAY736 Serum Concentration - AUClast
Description	The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration [mass × time / volume]. The concentration of VAY736 was measured in the serum.
Time Frame	predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Outcome Measure Data

Analysis Population Description

PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo
Measure Participants	7	2	0
Mean (Standard Deviation) [day*ug/mL]	440 (114)	1480 (231)

6. Secondary Outcome

Title	VAY736 Serum Concentration - Cmax
Description	The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum.
Time Frame	predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Outcome Measure Data

Analysis Population Description

PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo
Measure Participants	7	2	0
Mean (Standard Deviation) [ug/mL]	77.1 (13.0)	230 (2.83)

7. Secondary Outcome

Title	VAY736 Serum Concentration - Tmax
Description	Tmax is the time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum.
Time Frame	predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Outcome Measure Data

Analysis Population Description

PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo
Measure Participants	7	2	0
Median (Full Range) [Hours]	2.05	2.11

8. Secondary Outcome

Title	VAY736 Serum Concentration - T1/2
Description	T1/2 is the terminal elimination half-life [time]. The concentration of VAY736 was measured in the serum.
Time Frame	predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Outcome Measure Data

Analysis Population Description

PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

Arm/Group Title	VAY736 3 mg/kg	VAY736 10 mg/kg	Placebo
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg	single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo	single dose iv of Placebo
Measure Participants	7	2	0
Mean (Standard Deviation) [Days]	11.2 (2.01)	15.4 (1.93)

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study for up to 5 years.
Adverse Event Reporting Description	Any sign or symptom until end of study for up to 5 years.
Arm/Group Title	VAY736 3 mg/kg		VAY736 10 mg/kg		Placebo		Open Label VAY736 10 mg/kg
Arm/Group Description	single dose iv of VAY736 at a dose of 3mg/kg		single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo		single dose iv of Placebo		Patients randomized to placebo in period 1 received open label VAY736 10mg/kg at week 24.
All Cause Mortality
	VAY736 3 mg/kg		VAY736 10 mg/kg		Placebo		Open Label VAY736 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Serious Adverse Events
	VAY736 3 mg/kg		VAY736 10 mg/kg		Placebo		Open Label VAY736 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		0/2 (0%)		1/4 (25%)		1/3 (33.3%)
Eye disorders
Cataract	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Duodenal ulcer	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Pemphigus	0/7 (0%)		0/2 (0%)		1/4 (25%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	VAY736 3 mg/kg		VAY736 10 mg/kg		Placebo		Open Label VAY736 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/7 (85.7%)		2/2 (100%)		3/4 (75%)		3/3 (100%)
Cardiac disorders
Arrhythmia	0/7 (0%)		0/2 (0%)		1/4 (25%)		0/3 (0%)
Eye disorders
Conjunctivitis allergic	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Diarrhoea	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Flatulence	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Gingival recession	0/7 (0%)		0/2 (0%)		1/4 (25%)		0/3 (0%)
Nausea	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Oral pain	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Toothache	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
General disorders
Chills	0/7 (0%)		1/2 (50%)		0/4 (0%)		0/3 (0%)
Fatigue	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Influenza like illness	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Pain	0/7 (0%)		1/2 (50%)		0/4 (0%)		0/3 (0%)
Pyrexia	0/7 (0%)		1/2 (50%)		0/4 (0%)		0/3 (0%)
Infections and infestations
Bronchitis	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Dermatophytosis of nail	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Herpes simplex	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Impetigo	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Laryngitis	0/7 (0%)		0/2 (0%)		1/4 (25%)		0/3 (0%)
Nasopharyngitis	1/7 (14.3%)		0/2 (0%)		1/4 (25%)		1/3 (33.3%)
Oral fungal infection	0/7 (0%)		0/2 (0%)		1/4 (25%)		0/3 (0%)
Otitis media	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Paronychia	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Rhinitis	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Tooth abscess	0/7 (0%)		1/2 (50%)		0/4 (0%)		0/3 (0%)
Upper respiratory tract infection	1/7 (14.3%)		1/2 (50%)		0/4 (0%)		0/3 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	0/7 (0%)		1/2 (50%)		0/4 (0%)		0/3 (0%)
Investigations
Amylase increased	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Blood bilirubin increased	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Blood calcium decreased	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Blood magnesium decreased	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Blood potassium increased	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Lipase increased	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Back pain	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Osteoarthritis	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Pain in extremity	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Nervous system disorders
Dizziness	1/7 (14.3%)		1/2 (50%)		0/4 (0%)		0/3 (0%)
Headache	2/7 (28.6%)		1/2 (50%)		0/4 (0%)		1/3 (33.3%)
Sciatica	0/7 (0%)		1/2 (50%)		0/4 (0%)		0/3 (0%)
Psychiatric disorders
Insomnia	2/7 (28.6%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/7 (42.9%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Dysphonia	0/7 (0%)		0/2 (0%)		1/4 (25%)		0/3 (0%)
Dyspnoea	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Oropharyngeal pain	2/7 (28.6%)		1/2 (50%)		0/4 (0%)		1/3 (33.3%)
Rhinorrhoea	0/7 (0%)		1/2 (50%)		0/4 (0%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Dermatitis	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Mechanical urticaria	0/7 (0%)		0/2 (0%)		0/4 (0%)		1/3 (33.3%)
Rash	1/7 (14.3%)		0/2 (0%)		0/4 (0%)		0/3 (0%)
Vascular disorders
Orthostatic hypotension	0/7 (0%)		1/2 (50%)		0/4 (0%)		0/3 (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 (ie, data from all sites) in the clinical trial.