Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Valsartan (VAL489), Valsartan and simvastatin
Valsartan · 48 trials · 12 indications
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.
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.
Three arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSDBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and center (pooled as appropriate) as factors and centered baseline MSDBP as a covariate.
Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participant remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 1-2 minute intervals and the mean of three sitting systolic blood pressure (SSBP) measurements were used as the average sitting office blood pressure for that visit. Negative change from Baseline indicates improvement.
Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participant remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 1-2 minute intervals and the mean of three SDBP measurements were used as the average sitting office blood pressure for that visit. Negative change from Baseline indicates improvement.
An AE was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes.
No new unexpected AE's were observed in long-term treatment with VAA 80/5 mg. There were no deaths during the study. The SAEs were rare, with 9 patients (2.5%) reporting 10 events (1 patient experienced 2 SAEs). These events were not clustered to any particular primary system organ class and only 2 events the investigators could not excluded a relationship to study drug. The events that occurred were expected in this study population and/or were known to be associated with either valsartan or amlodipine. AEs leading to discontinuation occurred in 14 patients (3.8%).
Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was \< 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.
Only occurrences of peripheral edema quantified as a reported adverse event coded as peripheral edema were included in the analysis. If a patient experienced more than one occurrence of peripheral edema between Day 1 and Week 8, it was only counted once in the analysis.
Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.
Progression to diabetes was determined by (a) an algorithm based on central laboratory measurements of fasting plasma glucose and/or a 2 hour oral glucose tolerance test or (b) adjudication by the Diabetes Endpoint Adjudication Committee.
The extended cardiovascular endpoint was defined as a cardiovascular morbidity/mortality event including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, revascularization procedure, hospitalization for congestive heart failure, and hospitalization for unstable angina.
The core cardiovascular endpoint was defined as a cardiovascular morbidity/mortality event including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure.
Progression to diabetes was determined by (a) an algorithm based on central laboratory measurements of fasting plasma glucose and/or a 2 hour oral glucose tolerance test or (b) adjudication by the Diabetes Endpoint Adjudication Committee.
The extended cardiovascular endpoint was defined as a cardiovascular morbidity/mortality event including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, revascularization procedure, hospitalization for congestive heart failure, and hospitalization for unstable angina.
The core cardiovascular endpoint was defined as a cardiovascular morbidity/mortality event including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure.
Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 1
| Arm | Type | Description |
|---|---|---|
| valsartan | EXPERIMENTAL | 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 160 mg | ACTIVE_COMPARATOR | One capsule Valsartan 160 mg and 1 tablet placebo to Valsartan/Amlodipine taken orally once daily at approximately 9:00 AM for 8 weeks |
| Valsartan/amlodipine 160/5 mg | EXPERIMENTAL | One film-coated tablet Valsartan/amlodipine 160/5 mg and 1 capsule Placebo to Valsartan taken orally once daily at approximately 9:00 AM for 8 weeks |
| Single-Blind Run-In Valsartan 160 mg | OTHER | Single-Blind Run-In treatment with one capsule Valsartan 160 mg taken orally once daily at approximately 9:00 AM for 4 weeks. |
| 1 | ACTIVE_COMPARATOR | - |
| 2 | ACTIVE_COMPARATOR | - |
| 3 | ACTIVE_COMPARATOR | - |
| 4 | EXPERIMENTAL | - |
| CKD patients: Valsartan+enalapril | EXPERIMENTAL | - |
| CKD patients: Enalapril | ACTIVE_COMPARATOR | - |
| Non-CKD patients: Valsartan | EXPERIMENTAL | - |
| Non-CKD patients: Enalapril | ACTIVE_COMPARATOR | - |
| Valsartan Open Label | EXPERIMENTAL | Extemporaneous oral suspension prepared from valsartan tablets was administered to participants once daily. The starting dose of valsartan was 1 mg/kg, escalated to 2 mg/kg or 4 mg/kg based on mean sitting systolic blood pressure (MSSBP) control after 2 weeks up to 18 weeks. |
| Amlodipine + Valsartan | EXPERIMENTAL | Participants received 160 mg Valsartan and 5 mg amlodipine orally once a day for 52 weeks. If blood pressure was not normalized at week 4, treatment was uptitrated to valsartan/amlodipine 160/10 mg. Participants with still uncontrolled hypertension could receive add-on antihypertensive medication. |
| Losartan + Hydrochlorothiazide | ACTIVE_COMPARATOR | Participants received 100 mg losartan and 12.5 mg Hydrochlorothiazide (HCT) orally once a day for 52 weeks. If blood pressure was not normalized at week 4, treatment was uptitrated to losartan/HCT 100/25 mg, respectively, until end of study. Participants with still uncontrolled hypertension could receive add-on antihypertensive medication. |
| Low Dose | EXPERIMENTAL | - |
| Medium Dose | EXPERIMENTAL | - |
| High Dose | EXPERIMENTAL | - |
| Valsartan + Amlodipine 80/5 mg | EXPERIMENTAL | Valsartan 80 mg or Amlodipine 5 mg ---\> Valsartan + Amlodipine 80 / 5 mg |
| Valsartan + Amlodipine 80/5 mg + Diuretic | EXPERIMENTAL | Valsartan + Amlodipine 80 / 5 mg + Diuretic |
| Amlodipine 10 mg | ACTIVE_COMPARATOR | Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator. |
| Valsartan 80 mg | EXPERIMENTAL | - |
| Valsartan 320 mg | EXPERIMENTAL | - |
| Enalapril 10 mg | ACTIVE_COMPARATOR | - |
| Enalapril 20 mg | ACTIVE_COMPARATOR | - |
| Enalapril 40 mg | ACTIVE_COMPARATOR | - |
| Valsartan/amlodipine 80/5 mg | EXPERIMENTAL | - |
| Amlodipine 5 mg | ACTIVE_COMPARATOR | - |
| Valsartan 160 mg + nateglinide 60 mg | EXPERIMENTAL | For the first 2 weeks of treatment, patients took the combination of nateglinide 30 mg (3 times daily, ante cibum \[ac\] before meals) and valsartan 80 mg (once daily \[od\] in the morning). After 2 weeks, patients were up-titrated to nateglinide 60 mg ac and valsartan 160 mg od. |
| Valsartan 160 mg + nateglinide placebo | EXPERIMENTAL | For the first 2 weeks of treatment, patients took valsartan 80 mg capsules (once daily \[od\] in the morning). After 2 weeks, patients were up-titrated to 160 mg valsartan od. Patients also received nateglinide placebo tablets (3 times daily, ante cibum \[ac\] before meals). |
| Nateglinide 60 mg + valsartan placebo | EXPERIMENTAL | For the first 2 weeks of treatment, patients took nateglinide 30 mg tablets (3 times daily, ante cibum \[ac\] before meals). After 2 weeks, patients were uptitrated to 60 mg nateglinide ac. Patients also received valsartan placebo capsules (once daily \[od\] in the morning). |
| Placebo | PLACEBO_COMPARATOR | Patients took 3 nateglinide placebo tablets (3 times daily, ante cibum \[ac\] before meals) and 1 valsartan placebo capsule (once daily \[od\] in the morning). |
| LCZ696 followed by Valsartan | EXPERIMENTAL | Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks |
| Valsartan followed by LCZ696 | EXPERIMENTAL | Period 1: Valsartan 320mg QD for 4 weeks then washout followed by Period 2: LCZ696 400mg QD for 4 weeks |
| Valsartan + amlodipine 40/2.5 mg | EXPERIMENTAL | - |
| Valsartan + amlodipine 40/5 mg | EXPERIMENTAL | - |
| Valsartan + amlodipine 80/2.5 mg | EXPERIMENTAL | - |
| Valsartan 40 mg | ACTIVE_COMPARATOR | - |
| Amlodipine 2.5 mg | ACTIVE_COMPARATOR | - |
| Valsartan 20 mg or 40 mg | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Valsartan | DRUG | week 1: 40/80/160 week 2-78: 80/160/320mg, oral, by mouth, once daily |
| amlodipine | DRUG | added to valsartan after week 8 if the MSSBP and/or MSDBP was higher than 95th percentile for age, gender and height under the maintenance valsartan dose |
| Hydrochlorothiazide | DRUG | added to valsartan after week 8 if the MSSBP and/or MSDBP was higher than 95th percentile for age, gender and height under the maintenance valsartan dose |
| Valsartan/amlodipine 160/5 mg | DRUG | Valsartan/amlodipine 160/5mg film coated tablets taken orally once daily. |
| Valsartan 160 mg | DRUG | Valsartan 160 mg capsule taken orally once daily. |
| Placebo | DRUG | 1 capsule or tablet taken orally once daily |
| Valsartan/hydrochlorothiazide (HCTZ) | DRUG | - |
| Valsartan/amlodipine | DRUG | - |
| Amlodipine/hydrochlorothiazide(HCTZ) | DRUG | - |
| Valsartan/amlodipine/hydrochlorothiazide(HCTZ) | DRUG | - |
| Enalapril | DRUG | Enalapril (10, 20, and 40 mg, weight stratified). All study medications were taken orally once daily, at approximately the same time each day, with or without food. |
| placebo matched to enalapril | DRUG | Placebo matched to enalapril. All study medications were taken orally once daily, at approximately the same time each day, with or without food. |
| placebo matched to valsartan | DRUG | placebo matched to valsartan. All study medications were taken orally once daily, at approximately the same time each day, with or without food. |
| Losartan | DRUG | 100 mg tablets taken orally once daily in the morning. |
| Valsartan 0.25 mg/kg | DRUG | once daily |
| Valsartan 1.0 mg/kg | DRUG | once daily |
| Valsartan 4.0 mg/kg | DRUG | once daily |
| Valsartan + Amlodipine besilate | DRUG | During the run-in period, either Valsartan 80 mg or Amlodipine 5 mg tablet was given once daily. Throughout the Valsartan + Amlodipine treatment period, a Valsartan + Amlodipine tablet 80/5 mg was given once daily at around 8:00 AM in the morning. |
| Valsartan 160 mg capsules | DRUG | - |
| Amlodipine 5 mg capsules | DRUG | - |
| Valsartan/amlodipine 80/5 mg | DRUG | 1 valsartan/amlodipine 80/5 mg tablet, 1 placebo capsule to match valsartan once daily |
| Valsartan 80 mg | DRUG | 1 valsartan 80 mg capsule, 1 placebo tablet to match valsartan/amlodipine 80/5 mg once daily |
| Amlodipine 5 mg | DRUG | 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures. |
| valsartan + amlodipine | DRUG | - |
| Valsartan plus Hydrochlorothiazide | DRUG | - |
| Candesartan plus Hydrochlorothiazide | DRUG | - |
| Valsartan + HCTZ | DRUG | - |
| Amlodipine + HCTZ | DRUG | - |
| Valsartan + amlodipine + HCTZ | DRUG | - |
| Valsartan + Hydrochlorothiazide | DRUG | - |
| simvastatin | DRUG | - |
| valsartan + simvastatin | DRUG | - |
| lisinopril | DRUG | - |
| irbesartan | DRUG | - |
| valsartan+amlodipine combination | DRUG | - |
| VALSARTAN, VALSARTAN+HYDROCHLOROTHIAZIDE | DRUG | - |
| valsartan+amlodipine | DRUG | - |
| valsartan+amlodipine combination, valsartan, amlodipine | DRUG | - |
| Valsartan 160 mg + nateglinide 60 mg | DRUG | The double-blinding of the randomized study medication was maintained by the use of identical placebo and active tablets and capsules for nateglinide and valsartan, respectively. Patients were instructed not to take the morning dose of either medication nor to eat breakfast on the day of a scheduled study visit, but to wait until after the visit was completed. Patients not tolerating the higher dose (Level 2) were down-titrated to receive Level 1. Patients not tolerating the lower dose (Level 1) had a treatment interruption. Starting at Week 2 and throughout the study, attempts were to be made to reach the highest dose level (Level 2), if medically acceptable. Following each change in dose level or re-initiation of treatment, tolerability was assessed after 2 weeks of exposure. |
| Valsartan 160 mg + nateglinide placebo | DRUG | The double-blinding of the randomized study medication was maintained by the use of identical placebo and active tablets and capsules for nateglinide and valsartan, respectively. Patients were instructed not to take the morning dose of either medication nor to eat breakfast on the day of a scheduled study visit, but to wait until after the visit was completed. Patients not tolerating the higher dose (Level 2) were down-titrated to receive Level 1. Patients not tolerating the lower dose (Level 1) had a treatment interruption. Starting at Week 2 and throughout the study, attempts were to be made to reach the highest dose level (Level 2), if medically acceptable. Following each change in dose level or re-initiation of treatment, tolerability was assessed after 2 weeks of exposure. |
| Nateglinide 60 mg + valsartan placebo | DRUG | The double-blinding of the randomized study medication was maintained by the use of identical placebo and active tablets and capsules for nateglinide and valsartan, respectively. Patients were instructed not to take the morning dose of either medication nor to eat breakfast on the day of a scheduled study visit, but to wait until after the visit was completed. Patients not tolerating the higher dose (Level 2) were down-titrated to receive Level 1. Patients not tolerating the lower dose (Level 1) had a treatment interruption. Starting at Week 2 and throughout the study, attempts were to be made to reach the highest dose level (Level 2), if medically acceptable. Following each change in dose level or re-initiation of treatment, tolerability was assessed after 2 weeks of exposure. |
| Valsartan placebo + nateglinide placebo | DRUG | The double-blinding of the randomized study medication was maintained by the use of identical placebo and active tablets and capsules for nateglinide and valsartan, respectively. Patients were instructed not to take the morning dose of either medication nor to eat breakfast on the day of a scheduled study visit, but to wait until after the visit was completed. Patients not tolerating the higher dose (Level 2) were down-titrated to receive Level 1. Patients not tolerating the lower dose (Level 1) had a treatment interruption. Starting at Week 2 and throughout the study, attempts were to be made to reach the highest dose level (Level 2), if medically acceptable. Following each change in dose level or re-initiation of treatment, tolerability was assessed after 2 weeks of exposure. |
| Valsartan and simvastatin | DRUG | - |
| LCZ696 | DRUG | LCZ696 400mg tablet once daily |
| Valsartan + amlodipine 40/2.5 mg | DRUG | Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily |
| Valsartan + amlodipine 40/5 mg | DRUG | Valsartan + amlodipine 40/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily |
| Valsartan + amlodipine 80/2.5 mg | DRUG | Valsartan + amlodipine 80/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily |
| Valsartan + amlodipine 80/5 mg | DRUG | Valsartan + amlodipine 80/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily |
| Valsartan 40 mg | DRUG | Valsartan 40 mg tablet plus 3 tablet and 2 capsule placebos taken once daily |
| Amlodipine 2.5 mg | DRUG | Amlodipine 2.5 mg capsule plus 4 tablet and 1 capsule placebos taken once daily |
| valsartan 160 mg BID | DRUG | - |
| Valsartan (VAL489) | DRUG | - |
Inclusion Criteria: * Documented diagnosis of hypertension * able to swallow a tablet * body weight ≥18 kg and ≤160 kg at baseline * MSSBP must be ≥ 95th percentile and ≤25% above the 95th percentile for age, gender and height. Exclusion Criteria: * Any clinically significant physical abnormaliti...