Safety and Efficacy Study of LHW090 in Resistant Hypertension Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02515331
• Collaborator: (none)
• Enrollment: 64
• Locations: 16
• Arms: 3
• Actual Duration (Months): 21.4
• Patients Per Site: 4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the present study was to determine whether LHW090 displays the clinical safety and efficacy profile to support further development in patients with resistant hypertension.

Condition or Disease	Intervention/Treatment	Phase
Patients, Resistant Hypertension	Drug: LHW090; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Sponsor Open, Site and Subject Double Blind, Parallel Group, Placebo-controlled Study to Evaluate the Safety and Efficacy of LHW090 After 4 Weeks Treatment in Patients With Resistant Hypertension
• Actual Study Start Date: Nov 4, 2015
• Actual Primary Completion Date: Aug 17, 2017
• Actual Study Completion Date: Aug 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LHW090 100 mg LHW090 100 mg once daily for 28 days	Drug: LHW090; Capsule - oral dose
Experimental: LHW090 200 mg LHW090 200 mg once daily for 28 days	Drug: LHW090; Capsule - oral dose
Placebo Comparator: Placebo Matching placebo to LHW090 oral dose for 28 days	Drug: Placebo; Capsule - oral dose

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Reported Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths [6 months]

   Number of participants with AEs, SAEs and deaths were assessed.

2. Change From Baseline in Mean Daytime Blood Pressure [Baseline, day 27]

   Change in the 12 hour average of systolic blood pressure (SBP) measured by ambulatory blood pressure was defined as the 12 hour daytime average SBP on Day 28 minus the 12 hour daytime average SBP on Day -1. monitoring (ABPM). A negative change from baseline indicates improvement.

Secondary Outcome Measures

1. Pharmacokinetics of LHW090/LHV527 in Plasma: Observe Maximum Plasma Concentration Following LHW090 at Steady State in Patients (Cmax) [Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28]

   Blood samples were collected to assess Cmax.

2. Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (Tmax) [Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28]

   Blood samples were collected to assess Tmax.

3. Pharmacokinetics of LHW090/LHV527 in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) [Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28]

   Blood samples were collected to assess AUClast.

4. Pharmacokinetics of LHW090/LHV527 in Plasma: Last Measurable Plasma Concentration (Clast) [Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28]

   Blood samples were collected to assess Clast.

5. Pharmacokinetics of LHW090/LHV527 in Plasma:Tlast [Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28]

   Blood samples were collected to assess Tlast.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female patients, age 40 to 85 years inclusive.

• • Patients with uncontrolled hypertension (here defined as having a mean daytime systolic BP ≥ 135 mmHg by ABPM at screening) despite treatment with a stable (at least 1 month) regimen that includes an optimal dose of an ARB plus a diuretic plus at least one additional class of anti-hypertensive medication.

For the purposes of this trial, optimal doses of anti-hypertensive medications are defined as:

• the highest dose listed in the clinical practice guideline from the American Society for Hypertension and the International Society for Hypertension or

• the highest allowable prescribed dose per the manufacturer's label or

• the highest dose tolerated by an individual patient or

• the highest dose appropriate for an individual patient in the judgment of the Investigator

• Subjects must weigh at least 45 kg to participate in the study and must have a body mass index (BMI) within the range of 18-38 kg/m^2.

Exclusion Criteria:

• Patients with an estimated GFR <60 ml/min/1.73m^2.

• Use of angiotensin converting enzyme inhibitors (ACE-inhibitors). Note: Patients who discontinue their ACE-inhibitor and substitute with an angiotensin receptor blocker may be eligible to be re-screened provided their anti-hypertensive regimen has been stable for at least 1 month. Any substitutions or changes to a patient's anti-hypertensive regimen should be done under the guidance of the patient's treating physician.

• Severe hypertension as defined by systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg at screening.

• A history of secondary hypertension of any etiology including but not limited to unilateral or bilateral renal artery stenosis, polycystic kidney disease, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, and drug-induced hypertension.

• Known current significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or significant severe valvular disease on prior or current echocardiogram).

• A history of known moderate or malignant retinopathy defined as moderate (retinal signs of hemorrhage), microaneurysms, cotton-wool spots, hard exudates, or a combination thereof) or malignant (signs of moderate retinopathy plus swelling of the optic disk). Patients with a stable ophthalmologic history in the past 6 months are eligible.

• To facilitate ABPM assessment, an upper arm circumference greater than 42 cm.

• History within the previous 6 months of myocardial infarction, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), hypertensive encephalopathy, stroke, or transient ischemic attack (TIA).

Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

• Women of child-bearing potential

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35294
2	Novartis Investigative Site	North Hollywood	California	United States	91606
3	Novartis Investigative Site	Atlantis	Florida	United States	33462
4	Novartis Investigative Site	Daytona Beach	Florida	United States	32117
5	Novartis Investigative Site	Jacksonville	Florida	United States	32216
6	Novartis Investigative Site	Honolulu	Hawaii	United States	96814
7	Novartis Investigative Site	Knoxville	Tennessee	United States	37920
8	Novartis Investigative Site	Gentofte		Denmark	DK 2820
9	Novartis Investigative Site	Paris		France	75015
10	Novartis Investigative Site	Berlin		Germany	10098
11	Novartis Investigative Site	Duesseldorf		Germany	40225
12	Novartis Investigative Site	Hannover		Germany	30625
13	Novartis Investigative Site	Homburg		Germany	66421
14	Novartis Investigative Site	Meibergdreef 9		Netherlands	1105 AZ
15	Novartis Investigative Site	Basel		Switzerland	4031
16	Novartis Investigative Site	Lausanne		Switzerland	1011

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Aug 22, 2016
• Statistical Analysis Plan - Aug 22, 2016

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02515331
• Other Study ID Numbers: CLHW090X2202; 2015-001890-42
• First Posted: Aug 4, 2015
• Last Update Posted: Jan 5, 2021
• Last Verified: Jun 1, 2018

• Keywords provided by Novartis Pharmaceuticals: resistant hypertension
• Additional relevant MeSH terms: Hypertension

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized in a 1:1:2 ratio to LHW090 100 mg, LHW090 200 mg and placebo, respectively.

Arm/Group Title	LHW090 100 mg	LHW090 200 mg	Placebo
Arm/Group Description	LHW090 100 mg once daily for 28 days	LHW090 200 mg once daily for 28 days	Matching placebo to LHW090 oral dose for 28 days
Period Title: Overall Study
STARTED	17	15	32
Primary Pharmacodynamic Analysis Set	15	14	29
Pharmacokinetic (PK) Analysis Set	17	15	0
COMPLETED	15	15	28
NOT COMPLETED	2	0	4

Baseline Characteristics

Arm/Group Title	LHW090 100 mg	LHW090 200 mg	Placebo	Total
Arm/Group Description	LHW090 100 mg once daily for 28 days	LHW090 200 mg once daily for 28 days	Matching placebo to LHW090 oral dose for 28 days	Total of all reporting groups
Overall Participants	17	15	32	64
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.2 (8.42)	61.8 (5.16)	64.4 (9.56)	63.8 (8.38)
Sex: Female, Male (Count of Participants)
Female	4 23.5%	9 60%	13 40.6%	26 40.6%
Male	13 76.5%	6 40%	19 59.4%	38 59.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 5.9%	0 0%	0 0%	1 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	4 23.5%	7 46.7%	14 43.8%	25 39.1%
White	11 64.7%	7 46.7%	18 56.3%	36 56.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 5.9%	1 6.7%	0 0%	2 3.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Reported Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths
Description	Number of participants with AEs, SAEs and deaths were assessed.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Safety analysis set: included all participants who were randomized.

Arm/Group Title	LHW090 100 mg	LHW090 200 mg	Placebo
Arm/Group Description	LHW090 100 mg once daily for 28 days	LHW090 200 mg once daily for 28 days	Matching placebo to LHW090 oral dose for 28 days
Measure Participants	17	15	32
AEs	12 70.6%	3 20%	14 43.8%
SAEs	0 0%	0 0%	0 0%
Deaths	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Change From Baseline in Mean Daytime Blood Pressure
Description	Change in the 12 hour average of systolic blood pressure (SBP) measured by ambulatory blood pressure was defined as the 12 hour daytime average SBP on Day 28 minus the 12 hour daytime average SBP on Day -1. monitoring (ABPM). A negative change from baseline indicates improvement.
Time Frame	Baseline, day 27

Outcome Measure Data

Analysis Population Description

The primary pharmacodynamics (PD) analysis set, which included patients that received study drug with any available PD data, was considered for the analysis. Only patients with values on both baseline and day 27 were analyzed.

Arm/Group Title	LHW090 100 mg	LHW090 200 mg	Placebo
Arm/Group Description	LHW090 100 mg once daily for 28 days	LHW090 200 mg once daily for 28 days	Matching placebo to LHW090 oral dose for 28 days
Measure Participants	15	13	28
Mean (Standard Deviation) [mmHg]	-9.41 (8.379)	-16.84 (7.678)	-0.79 (10.555)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LHW090 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	1-sided p-value
	Method	Longitudinal repeated measures mixed eff
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.555
	Confidence Interval	(2-Sided) 95%; -14.388 to -2.722
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9077
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LHW090 200 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	1-sided p-value
	Method	Longitudinal repeated measures mixed eff
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-14.727
	Confidence Interval	(2-Sided) 95%; -20.852 to -8.602
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0548
	Estimation Comments

3. Secondary Outcome

Title	Pharmacokinetics of LHW090/LHV527 in Plasma: Observe Maximum Plasma Concentration Following LHW090 at Steady State in Patients (Cmax)
Description	Blood samples were collected to assess Cmax.
Time Frame	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28

Outcome Measure Data

Analysis Population Description

The PK analysis set, which included participants with at least one valid PK concentration measurement and no major protocol deviations affecting PK data, was considered. Only participants with available PK data were analyzed.

Arm/Group Title	LHW090 100 mg	LHW090 200 mg
Arm/Group Description	LHW090 100 mg once daily for 28 days	LHW090 200 mg once daily for 28 days
Measure Participants	17	15
LHW090, day 1	3620 (1220)	6340 (3440)
LHW090, day 28	4190 (1740)	7340 (4300)
LHV527, day 1	5040 (1770)	6330 (3700)
LHV527, day 28	5240 (1960)	9870 (1810)

4. Secondary Outcome

Title	Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (Tmax)
Description	Blood samples were collected to assess Tmax.
Time Frame	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28

Outcome Measure Data

Analysis Population Description

The PK analysis set, which included participants with at least one valid PK concentration measurement and no major protocol deviations affecting PK data, was considered. Only participants with available PK data were analyzed.

Arm/Group Title	LHW090 100 mg	LHW090 200 mg
Arm/Group Description	LHW090 100 mg once daily for 28 days	LHW090 200 mg once daily for 28 days
Measure Participants	17	15
LHW090, day 1	2.08	3.00
LHW090, day 28	2.00	2.92
LHV527, day 1	3.07	4.08
LHV527, day 28	3.92	4.00

5. Secondary Outcome

Title	Pharmacokinetics of LHW090/LHV527 in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast)
Description	Blood samples were collected to assess AUClast.
Time Frame	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28

Outcome Measure Data

Analysis Population Description

The PK analysis set, which included participants with at least one valid PK concentration measurement and no major protocol deviations affecting PK data, was considered. Only participants with available PK data were analyzed.

Arm/Group Title	LHW090 100 mg	LHW090 200 mg
Arm/Group Description	LHW090 100 mg once daily for 28 days	LHW090 200 mg once daily for 28 days
Measure Participants	17	15
LHW090, day 1	12300 (3870)	24500 (16000)
LHW090, day 28	13700 (4370)	24400 (11400)
LHV527, day 1	25300 (11800)	28700 (17900)
LHV527, day 28	27700 (11600)	52300 (14400)

6. Secondary Outcome

Title	Pharmacokinetics of LHW090/LHV527 in Plasma: Last Measurable Plasma Concentration (Clast)
Description	Blood samples were collected to assess Clast.
Time Frame	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28

Outcome Measure Data

Analysis Population Description

The PK analysis set, which included participants with at least one valid PK concentration measurement and no major protocol deviations affecting PK data, was considered. Only participants with available PK data were analyzed.

Arm/Group Title	LHW090 100 mg	LHW090 200 mg
Arm/Group Description	LHW090 100 mg once daily for 28 days	LHW090 200 mg once daily for 28 days
Measure Participants	17	15
LHW090, day 1	404 (358)	1710 (1600)
LHW090, day 28	682 (752)	1790 (1740)
LHV527, day 1	3490 (1700)	4670 (3050)
LHV527, day 28	3430 (1340)	7840 (3130)

7. Secondary Outcome

Title	Pharmacokinetics of LHW090/LHV527 in Plasma:Tlast
Description	Blood samples were collected to assess Tlast.
Time Frame	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28

Outcome Measure Data

Analysis Population Description

The PK analysis set, which included participants with at least one valid PK concentration measurement and no major protocol deviations affecting PK data, was considered. Only participants with available PK data were analyzed.

Arm/Group Title	LHW090 100 mg	LHW090 200 mg
Arm/Group Description	LHW090 100 mg once daily for 28 days	LHW090 200 mg once daily for 28 days
Measure Participants	17	15
LHW090, day 1	8.00	8.00
LHW090, day 28	8.00	8.00
LHV527, day 1	8.00	8.00
LHV527, day 28	8.00	8.00

Adverse Events

Time Frame	up to 28 days
Arm/Group Title	LHW090 100mg		LHW090 200mg		Placebo
Arm/Group Description	LHW090 100 mg once daily for 28 days		LHW090 200 mg once daily for 28 days		Matching placebo to LHW090 oral dose for 28 days
All Cause Mortality
	LHW090 100mg		LHW090 200mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/15 (0%)		0/32 (0%)
Serious Adverse Events
	LHW090 100mg		LHW090 200mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/15 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	LHW090 100mg		LHW090 200mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/17 (70.6%)		3/15 (20%)		14/32 (43.8%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Lymphadenopathy	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Thrombocytopenia	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Cardiac disorders
Sinus tachycardia	0/17 (0%)		1/15 (6.7%)		0/32 (0%)
Eye disorders
Eyelid oedema	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Photopsia	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Gastrointestinal disorders
Abdominal pain	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Constipation	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Diarrhoea	1/17 (5.9%)		1/15 (6.7%)		1/32 (3.1%)
Gastrointestinal motility disorder	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Gastrooesophageal reflux disease	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Haematochezia	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Haemorrhoids	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Nausea	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
General disorders
Asthenia	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Feeling hot	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Non-cardiac chest pain	0/17 (0%)		1/15 (6.7%)		0/32 (0%)
Oedema peripheral	2/17 (11.8%)		0/15 (0%)		3/32 (9.4%)
Immune system disorders
Hypersensitivity	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Infections and infestations
Eye infection	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Viral upper respiratory tract infection	0/17 (0%)		0/15 (0%)		2/32 (6.3%)
Injury, poisoning and procedural complications
Contusion	1/17 (5.9%)		0/15 (0%)		1/32 (3.1%)
Fall	1/17 (5.9%)		0/15 (0%)		1/32 (3.1%)
Investigations
Blood cholesterol increased	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Blood potassium increased	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Cardiac murmur	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Haematocrit increased	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Haemoglobin increased	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Weight increased	1/17 (5.9%)		0/15 (0%)		1/32 (3.1%)
Metabolism and nutrition disorders
Gout	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Hypercholesterolaemia	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Hypokalaemia	0/17 (0%)		0/15 (0%)		2/32 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Arthritis	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Back pain	0/17 (0%)		0/15 (0%)		2/32 (6.3%)
Muscular weakness	0/17 (0%)		1/15 (6.7%)		0/32 (0%)
Neck pain	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Pain in extremity	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Nervous system disorders
Headache	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Syncope	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Renal and urinary disorders
Pollakiuria	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Renal failure	1/17 (5.9%)		1/15 (6.7%)		1/32 (3.1%)
Urethral pain	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Reproductive system and breast disorders
Breast discomfort	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional	0/17 (0%)		1/15 (6.7%)		0/32 (0%)
Skin and subcutaneous tissue disorders
Dermatosis	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Erythema	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Pruritus	3/17 (17.6%)		0/15 (0%)		0/32 (0%)
Pruritus generalised	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Rash	1/17 (5.9%)		0/15 (0%)		0/32 (0%)
Skin discolouration	0/17 (0%)		0/15 (0%)		1/32 (3.1%)
Skin irritation	1/17 (5.9%)		0/15 (0%)		0/32 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.