Safety and Tolerability of Valsartan in Children 6 to 17 Years of Age

• ClinicalTrials.gov Identifier: NCT01365481
• Recruitment Status: Completed
• First Posted: June 3, 2011
• Results First Posted: April 21, 2016
• Last Update Posted: July 13, 2016
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Hypertension; Chronic Kidney Disease
• Interventions: Drug: Valsartan; Drug: amlodipine; Drug: Hydrochlorothiazide
• Enrollment: 150

Participant Flow

Recruitment Details	A 1 arm study of valsartan but with 2 groups for analyses. The valsartan +antihypertensive group includes the patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.
Pre-assignment Details	These 2 groups were not randomized and considered to be 2 different populations since the patients in the valsartan+antihypertensive group had concomitant antihypertensive usage per individual patient's conditions at any time during treatment period.

Arm/Group Title	CKD Patients: Valsartan + Antihypertensive Group	CKD Patients: Valsartan Alone	Non-CKD Patients: Valsartan + Antihypertensive Group	Non-CKD Patients: Valsartan Alone
Arm/Group Description	CKD Patients - Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	CKD Patients - Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.	Non-CKD patients-Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	Non-CKD patients-Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.
Period Title: Overall Study
Started	23	52	18	57
Completed	16	37	14	50
Not Completed	7	15	4	7
Reason Not Completed
Adverse Event	6	9	0	2
Withdrawal by Subject	0	2	1	1
Lost to Follow-up	1	1	2	3
Abnormal laboratory value(s)	0	1	0	0
Administrative problems	0	1	0	0
Protocol deviation	0	1	0	1
Unsatisfactory therapeutic effect	0	0	1	0

Baseline Characteristics

Arm/Group Title		CKD Patients: Valsartan + Antihypertensive Group	CKD Patients: Valsartan Alone	Non-CKD Patients: Valsartan + Antihypertensive Group	Non-CKD Patients: Valsartan Alone	Total
Arm/Group Description		CKD Patients - Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	CKD Patients - Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.	Non-CKD patients-Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	Non-CKD patients-Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.	Total of all reporting groups
Overall Number of Baseline Participants		23	52	18	57	150
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	23 participants	52 participants	18 participants	57 participants	150 participants
		12.90 (3.35)	12.30 (3.20)	13.79 (2.64)	14.37 (2.83)	13.36 (3.130)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	23 participants	52 participants	18 participants	57 participants	150 participants
6 – 11 years		10	22	3	10	45
12 – 17 years		13	30	15	47	105
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	52 participants	18 participants	57 participants	150 participants
	Female	12 52.2%	16 30.8%	3 16.7%	20 35.1%	51 34.0%
	Male	11 47.8%	36 69.2%	15 83.3%	37 64.9%	99 66.0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at End Point (Week 78 or Last Observation Carried Forward (LOCF)
Description	Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sSBP measurements were used as the average sitting office blood pressure for that visit.
Time Frame	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)

Outcome Measure Data

Analysis Population Description

The Full Analysis set (FAS) included all patients who entered the treatment period. ) This OM looked at the Valsartan + Antihypertensive and Valsartan alone for ALL patients and did not break up the analysis between CKD and non-CKD patients.

Arm/Group Title	Valsartan + Antihypertensive Group	Valsartan Alone
Arm/Group Description:	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.
Overall Number of Participants Analyzed	41	109
Mean (Standard Deviation); Unit of Measure: millimeter(s) of mercury (mmHg)
	-13.3 (13.69)	-15.5 (13.35)

2. Primary Outcome

Title	Change From Baseline in Mean Sitting Diastolic Blood Pressure (MsDBP) at End Point (Week 78 or Last Observation Carried Forward (LOCF)
Description	Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sDBP measurements were used as the average sitting office blood pressure for that visit.
Time Frame	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)

Outcome Measure Data

Analysis Population Description

The Full Analysis set (FAS) included all patients who entered the treatment period. ) This OM looked at the Valsartan + Antihypertensive and Valsartan alone for ALL patients and did not break up the analysis between CKD and non-CKD patients.

Arm/Group Title	Valsartan + Antihypertensive Group	Valsartan Alone
Arm/Group Description:	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.
Overall Number of Participants Analyzed	41	109
Mean (Standard Deviation); Unit of Measure: millimeter(s) of mercury (mmHg)
	-10.3 (11.94)	-10.8 (11.45)

3. Secondary Outcome

Title	Number of Participants With MSSBP, MSDBP and (MSSBP and MSDBP Combined) < 95th Percentile for Gender, Age, and Height
Description	Number of Participants with Mean sitting systolic (MSSBP) and mean sitting diastolic(MSDBP) blood pressure and both combined less than the 95th percentile for age, gender and height
Time Frame	End Point (Week 78 or Last observation carried forward (LOCF)

Outcome Measure Data

Analysis Population Description

The Full Analysis set (FAS) included all patients who entered the treatment period. This analysis includes only participants with baseline MSSBP or MSDBP or (MSSBP or MSDBP combined) ≥95th percentile for gender, age and height. n analyzed is displayed in left column. This OM did not break up the analysis between CKD and non-CKD patients.

Arm/Group Title	Valsartan + Antihypertensive Group	Valsartan Alone
Arm/Group Description:	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.
Overall Number of Participants Analyzed	41	109
Measure Type: Number; Unit of Measure: Number of Participants
MSSBP (n=39, 105)	23	90
MSDBP (n=28, 51)	20	47
MSSBP and MSDBP combined (n=40, 105)	22	88

4. Secondary Outcome

Title	Percentage of Chronic Kidney Disease (CKD) Patients Who Had >=50% Reduction in Urine Albumin/Creatinine Ratio (UACR) From Baseline to End Point
Description	Percentage of Patients with CKD who had Urine albumin creatinine reduction >/= 50% from baseline
Time Frame	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)

Outcome Measure Data

Analysis Population Description

The Safety set (SAF) included all patients who received at least one dose of study medication that has Chronic Kidney Disease (CKD) only

Arm/Group Title	Valsartan + Antihypertensive Group	Valsartan Alone
Arm/Group Description:	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.
Overall Number of Participants Analyzed	23	52
Measure Type: Number; Unit of Measure: Percentage of patients
	50.0	41.9

5. Secondary Outcome

Title	Percentage of Chronic Kidney Disease (CKD) Patients Who Had Estimated Glomerular Filtration Rate (eGFR) Decrease > 25 % From Baselinefrom Baseline to End Point
Description	Percentage of Patients with CKD who had eGFR decrease > 25 % from Baseline
Time Frame	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)

Outcome Measure Data

Analysis Population Description

The Safety set (SAF) included all patients who received at least one dose of study medication.that has Chronic Kidney Disease (CKD)

Arm/Group Title	Valsartan + Antihypertensive Group	Valsartan Alone
Arm/Group Description:	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.
Overall Number of Participants Analyzed	23	52
Measure Type: Number; Unit of Measure: Percentage of patients
	30.4	27.5

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Valsartan + Antihypertensive Group	Valsartan Alone	CKD Patients: Valsartan + Antihypertensive Group	CKD Patients: Valsartan Alone	Non-CKD Patients: Valsartan + Antihypertensive Group	Non-CKD Patients: Valsartan Alone
Arm/Group Description	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.	CKD Patients - Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	CKD Patients - Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.	Non-CKD patients-Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.	Non-CKD patients-Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg.
All-Cause Mortality
	Valsartan + Antihypertensive Group	Valsartan Alone	CKD Patients: Valsartan + Antihypertensive Group	CKD Patients: Valsartan Alone	Non-CKD Patients: Valsartan + Antihypertensive Group	Non-CKD Patients: Valsartan Alone
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events
	Valsartan + Antihypertensive Group	Valsartan Alone	CKD Patients: Valsartan + Antihypertensive Group	CKD Patients: Valsartan Alone	Non-CKD Patients: Valsartan + Antihypertensive Group	Non-CKD Patients: Valsartan Alone
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	8/41 (19.51%)	7/109 (6.42%)	7/23 (30.43%)	4/52 (7.69%)	1/18 (5.56%)	3/57 (5.26%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	1/41 (2.44%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
Gastrointestinal disorders
Oesophageal polyp † 1	1/41 (2.44%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
General disorders
Face oedema † 1	1/41 (2.44%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
Oedema peripheral † 1	1/41 (2.44%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
Hepatobiliary disorders
Cholelithiasis † 1	0/41 (0.00%)	1/109 (0.92%)	0/23 (0.00%)	0/52 (0.00%)	0/18 (0.00%)	1/57 (1.75%)
Infections and infestations
Gastroenteritis † 1	1/41 (2.44%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
Pneumonia † 1	1/41 (2.44%)	1/109 (0.92%)	1/23 (4.35%)	1/52 (1.92%)	0/18 (0.00%)	0/57 (0.00%)
Urinary tract infection † 1	0/41 (0.00%)	1/109 (0.92%)	0/23 (0.00%)	1/52 (1.92%)	0/18 (0.00%)	0/57 (0.00%)
Viral upper respiratory tract infection † 1	0/41 (0.00%)	1/109 (0.92%)	0/23 (0.00%)	0/52 (0.00%)	0/18 (0.00%)	1/57 (1.75%)
Investigations
Glomerular filtration rate decreased † 1	1/41 (2.44%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
Musculoskeletal and connective tissue disorders
Synovitis † 1	1/41 (2.44%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
Nervous system disorders
Somnolence † 1	0/41 (0.00%)	1/109 (0.92%)	0/23 (0.00%)	0/52 (0.00%)	0/18 (0.00%)	1/57 (1.75%)
Psychiatric disorders
Drug abuse † 1	0/41 (0.00%)	1/109 (0.92%)	0/23 (0.00%)	0/52 (0.00%)	0/18 (0.00%)	1/57 (1.75%)
Renal and urinary disorders
Chronic kidney disease † 1	1/41 (2.44%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
IgA nephropathy † 1	0/41 (0.00%)	1/109 (0.92%)	0/23 (0.00%)	1/52 (1.92%)	0/18 (0.00%)	0/57 (0.00%)
Lupus nephritis † 1	3/41 (7.32%)	1/109 (0.92%)	3/23 (13.04%)	1/52 (1.92%)	0/18 (0.00%)	0/57 (0.00%)
Nephrotic syndrome † 1	0/41 (0.00%)	1/109 (0.92%)	0/23 (0.00%)	1/52 (1.92%)	0/18 (0.00%)	0/57 (0.00%)
Neurogenic bladder † 1	0/41 (0.00%)	1/109 (0.92%)	0/23 (0.00%)	1/52 (1.92%)	0/18 (0.00%)	0/57 (0.00%)
Proteinuria † 1	1/41 (2.44%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
Vascular disorders
Hypertension † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Hypotension † 1	0/41 (0.00%)	1/109 (0.92%)	0/23 (0.00%)	0/52 (0.00%)	0/18 (0.00%)	1/57 (1.75%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Valsartan + Antihypertensive Group	Valsartan Alone	CKD Patients: Valsartan + Antihypertensive Group	CKD Patients: Valsartan Alone	Non-CKD Patients: Valsartan + Antihypertensive Group	Non-CKD Patients: Valsartan Alone
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	34/41 (82.93%)	68/109 (62.39%)	18/23 (78.26%)	36/52 (69.23%)	16/18 (88.89%)	32/57 (56.14%)
Blood and lymphatic system disorders
Lymphadenopathy † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Eye disorders
Myopia † 1	1/41 (2.44%)	1/109 (0.92%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	1/57 (1.75%)
Retinal vascular disorder † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Vision blurred † 1	2/41 (4.88%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	4/41 (9.76%)	7/109 (6.42%)	2/23 (8.70%)	4/52 (7.69%)	2/18 (11.11%)	3/57 (5.26%)
Abdominal pain upper † 1	2/41 (4.88%)	5/109 (4.59%)	2/23 (8.70%)	2/52 (3.85%)	0/18 (0.00%)	3/57 (5.26%)
Constipation † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Diarrhoea † 1	2/41 (4.88%)	8/109 (7.34%)	1/23 (4.35%)	5/52 (9.62%)	1/18 (5.56%)	3/57 (5.26%)
Nausea † 1	2/41 (4.88%)	3/109 (2.75%)	2/23 (8.70%)	2/52 (3.85%)	0/18 (0.00%)	1/57 (1.75%)
Toothache † 1	3/41 (7.32%)	1/109 (0.92%)	2/23 (8.70%)	0/52 (0.00%)	1/18 (5.56%)	1/57 (1.75%)
Vomiting † 1	5/41 (12.20%)	4/109 (3.67%)	4/23 (17.39%)	3/52 (5.77%)	1/18 (5.56%)	1/57 (1.75%)
General disorders
Asthenia † 1	2/41 (4.88%)	1/109 (0.92%)	1/23 (4.35%)	0/52 (0.00%)	1/18 (5.56%)	1/57 (1.75%)
Chest pain † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Pyrexia † 1	12/41 (29.27%)	18/109 (16.51%)	8/23 (34.78%)	12/52 (23.08%)	4/18 (22.22%)	6/57 (10.53%)
Infections and infestations
Acarodermatitis † 1	1/41 (2.44%)	1/109 (0.92%)	0/23 (0.00%)	1/52 (1.92%)	1/18 (5.56%)	0/57 (0.00%)
Enterobiasis † 1	1/41 (2.44%)	1/109 (0.92%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	1/57 (1.75%)
Influenza † 1	3/41 (7.32%)	1/109 (0.92%)	1/23 (4.35%)	0/52 (0.00%)	2/18 (11.11%)	1/57 (1.75%)
Mycoplasma infection † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Nasopharyngitis † 1	11/41 (26.83%)	22/109 (20.18%)	7/23 (30.43%)	14/52 (26.92%)	4/18 (22.22%)	8/57 (14.04%)
Pharyngitis † 1	2/41 (4.88%)	0/109 (0.00%)	2/23 (8.70%)	0/52 (0.00%)	0/18 (0.00%)	0/57 (0.00%)
Respiratory tract infection † 1	2/41 (4.88%)	4/109 (3.67%)	1/23 (4.35%)	0/52 (0.00%)	1/18 (5.56%)	4/57 (7.02%)
Rhinitis † 1	0/41 (0.00%)	3/109 (2.75%)	0/23 (0.00%)	0/52 (0.00%)	0/18 (0.00%)	3/57 (5.26%)
Upper respiratory tract infection † 1	2/41 (4.88%)	17/109 (15.60%)	1/23 (4.35%)	12/52 (23.08%)	1/18 (5.56%)	5/57 (8.77%)
Urinary tract infection † 1	2/41 (4.88%)	3/109 (2.75%)	2/23 (8.70%)	2/52 (3.85%)	0/18 (0.00%)	1/57 (1.75%)
Metabolism and nutrition disorders
Hyperkalaemia † 1	1/41 (2.44%)	4/109 (3.67%)	1/23 (4.35%)	4/52 (7.69%)	0/18 (0.00%)	0/57 (0.00%)
Hyperphosphataemia † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/41 (2.44%)	4/109 (3.67%)	1/23 (4.35%)	3/52 (5.77%)	0/18 (0.00%)	1/57 (1.75%)
Neck pain † 1	2/41 (4.88%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	2/18 (11.11%)	0/57 (0.00%)
Pain in extremity † 1	3/41 (7.32%)	0/109 (0.00%)	2/23 (8.70%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Nervous system disorders
Dizziness † 1	8/41 (19.51%)	17/109 (15.60%)	4/23 (17.39%)	6/52 (11.54%)	4/18 (22.22%)	11/57 (19.30%)
Headache † 1	14/41 (34.15%)	23/109 (21.10%)	8/23 (34.78%)	11/52 (21.15%)	6/18 (33.33%)	12/57 (21.05%)
Hypoaesthesia † 1	1/41 (2.44%)	1/109 (0.92%)	0/23 (0.00%)	1/52 (1.92%)	1/18 (5.56%)	0/57 (0.00%)
Renal and urinary disorders
Micturition urgency † 1	1/41 (2.44%)	1/109 (0.92%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	1/57 (1.75%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	18/41 (43.90%)	18/109 (16.51%)	12/23 (52.17%)	12/52 (23.08%)	6/18 (33.33%)	6/57 (10.53%)
Dyspnoea † 1	1/41 (2.44%)	2/109 (1.83%)	0/23 (0.00%)	2/52 (3.85%)	1/18 (5.56%)	0/57 (0.00%)
Epistaxis † 1	2/41 (4.88%)	1/109 (0.92%)	1/23 (4.35%)	0/52 (0.00%)	1/18 (5.56%)	1/57 (1.75%)
Nasal congestion † 1	3/41 (7.32%)	1/109 (0.92%)	1/23 (4.35%)	1/52 (1.92%)	2/18 (11.11%)	0/57 (0.00%)
Oropharyngeal pain † 1	2/41 (4.88%)	2/109 (1.83%)	1/23 (4.35%)	1/52 (1.92%)	1/18 (5.56%)	1/57 (1.75%)
Rhinitis allergic † 1	2/41 (4.88%)	0/109 (0.00%)	1/23 (4.35%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Rhinorrhoea † 1	4/41 (9.76%)	3/109 (2.75%)	3/23 (13.04%)	2/52 (3.85%)	1/18 (5.56%)	1/57 (1.75%)
Skin and subcutaneous tissue disorders
Acne † 1	1/41 (2.44%)	2/109 (1.83%)	0/23 (0.00%)	1/52 (1.92%)	1/18 (5.56%)	1/57 (1.75%)
Papule † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Pruritus † 1	0/41 (0.00%)	3/109 (2.75%)	0/23 (0.00%)	3/52 (5.77%)	0/18 (0.00%)	0/57 (0.00%)
Vascular disorders
Hypertension † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
Hypotension † 1	2/41 (4.88%)	2/109 (1.83%)	2/23 (8.70%)	2/52 (3.85%)	0/18 (0.00%)	0/57 (0.00%)
Pallor † 1	1/41 (2.44%)	0/109 (0.00%)	0/23 (0.00%)	0/52 (0.00%)	1/18 (5.56%)	0/57 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights 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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862 ­778 ­8300

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT01365481 History of Changes
• Other Study ID Numbers: CVAL489K2305; 2009-017594-37 ( EudraCT Number )
• First Submitted: May 9, 2011
• First Posted: June 3, 2011
• Results First Submitted: March 9, 2016
• Results First Posted: April 21, 2016
• Last Update Posted: July 13, 2016