Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as SPP100 (aliskiren), Aliskiren
SPP100 · 60 trials · 22 indications
Sitting blood pressure was measured at trough (24 hours ± 2 hours post dose) and recorded at all study visits. At the first study visit, blood pressure was measured in both arms and the arm with highest sitting DBP was found and used for all subsequent readings throughout the study. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these three sitting blood pressure measurements were used as the average sitting blood pressure for that visit. Analysis of covariance (ANCOVA) model contained treatment and region as two factors and baseline as a covariate.
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 1-2 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 1-2 minute intervals and the mean of three sSBP measurements were used as the average sitting office blood pressure for that visit.
Time to first confirmed occurrence of either cardiovascular death or heart failure re-hospitalization within 6 months of randomization was the primary efficacy variable. For the primary efficacy analysis, an event will be considered for the analysis if it occurs on or before Day 190 (189 days from randomization). The primary composite endpoint is the the composite of cardiovascular death or heart faliure re-hospitalization within 6 months.
Number of participants that had first occurrence of the composite endpoint, which is defined as either CV death or HF hospitalization due to HF.
Change from baseline in PAV for all matched slices of anatomically comparable segments of the target coronary artery were assessed by intravascular ultrasound (IVUS) evaluation after 104 weeks of treatment . calculation for change is the value at the later time point minus the value at the earlier time point, with positive numbers to represent increases and negative numbers to represent decreases
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Change in mean sitting systolic blood pressure (msSBP) from baseline to end of study (Week 8)
After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msDBP at baseline from the msDBP at 8 weeks was calculated using an Analysis of Covariance (ANCOVA) model with baseline as a covariate and treatment and region as two factors.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. An automated BP measurement device and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, diastolic BP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements.
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.
An AE was defined as the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug, even if the event is not considered to be related to study drug. An SAE was defined as an event which was fatal or life-threatening, resulted in persistent or significant disability/incapacity, constituted a congenital anomaly/birth defect, required inpatient hospitalization or prolongation of existing hospitalization, was medically significant, i.e. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above.
At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings.
To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint
To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint
To evaluate the non-inferiority of aliskiren 75 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint
Change from baseline to end of study in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal. Baseline LVESV was a covariate.
AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Efficacy of furosemide for sodium excretion (efficacy index 1) was defined by dividing urinary sodium excretion by the urinary excretion of furosemide. Diuretic index 1 for sodium was calculated for the for the total 0 to 4 hour urine collection.
Efficacy of furosemide for water excretion (efficacy index 2) was defined by dividing urine volume by the urinary excretion of furosemide.Diuretic index 2 for water was calculated for the 0 to 4 hour fraction urine collection.
Peripheral venous blood was collected after 30 minutes of rest in the sitting position for analysis of biomarkers. Geometric mean ratio to baseline at Week 12 for Venous angiotensin II levels was calculated in patients with decompensated systolic heart failure (SHF) and left ventricular ejection fraction ≤40% at 0 hour pre-dose, 3 hours and 24 hours post-dose.
The difference in resting vs. peak (85% of maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. Treadmill speed and incline were increased every 3 minutes until the patient was exhausted or peak HR was reached. The SBP at rest vs peak HR was recorded at Baseline and at Week 8 + 2 days (24-hrs after a missed dose); the change in rest vs. peak SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate.
MBF is measured by Positron Emission Tomography (PET) first at rest, then 45 minutes later, during cold pressor testing (CPT). The patient is placed in the PET scanner and injected with N-13 ammonia as a tracer. PET images are taken to assess myocardial blood flow at rest. After 40 minutes, the patient immerses one hand in ice water and PET images are taken to assess myocardial blood flow at sympathetic activation. Change from baseline data is analyzed by an analysis of variance (ANOVA) model including treatment and week as fixed factors and subject (nested in treatment) as a random factor.
Blood samples for the measurement of NT-proBNP were collected, processed, and shipped to the TIMI Biomarker Core Laboratory, Boston MA for storage and analysis. The change from baseline to Week 8 was expressed as the geometric mean of the ratio: Week 8/Baseline.
Pharmacokinetics (concentrations of aliskiren in blood and urine) of a single dose of aliskiren in End Stage Renal Disease (ESRD) patients on hemodialysis and matched healthy subjects was analyzed.
Pharmacokinetics (concentrations of aliskiren in blood and urine) of a single dose of aliskiren in End Stage Renal Disease (ESRD) patients on hemodialysis and matched healthy subjects was analyzed.
Pharmacokinetics (concentrations of aliskiren in blood and urine) of a single dose of aliskiren in End Stage Renal Disease (ESRD) patients on hemodialysis and matched healthy subjects was analyzed.
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. In single blind run-in (4 weeks) and double blind treatment period (8 weeks), patients were received matching placebo of aliskiren/amlodipine 150/5 mg tablet, aliskiren/amlodipine 150/2.5 mg tablet, aliskiren 150 mg tablet and two amlodipine 2.5 mg capsules once daily. |
| Aliskiren 150 mg | ACTIVE_COMPARATOR | In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Aliskiren 150 mg tablet once daily (o.d)+ placebo of two amlodipine 2.5 mg capsule o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period. |
| Amlodipine 2.5 mg | ACTIVE_COMPARATOR | In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Amlodipine 2.5 mg capsule once daily (o.d)+ placebo of amlodipine 2.5 mg capsule o.d., Aliskiren 150 mg o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period. |
| Amlodipine 5 mg | ACTIVE_COMPARATOR | In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received amlodipine 5 mg (two amlodipine 2.5 mg capsules o.d.)+ placebo of aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. , aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period. |
| Aliskiren/amlodipine 150/2.5 mg | EXPERIMENTAL | In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/2.5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. for 8 weeks of double blind period. |
| Aliskiren/amlodipine 150/5 mg | EXPERIMENTAL | In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period. |
| Aliskiren | EXPERIMENTAL | Patients will receive one of the following doses based on the their weight: Low weight (≥20 to \<50 kg) patients: Starting dose 37.5 mg with optional titration to 75 and then 150 mg Mid weight (≥50 to \<80 kg) patients: Starting dose 75 mg with optional titration to 150 and then 300 mg High weight (≥80 to ≤150 kg) patients: Starting dose 150 mg with optional titration to 300 and then 600 mg |
| Enalapril | ACTIVE_COMPARATOR | Patients will receive one of the following doses based on their weight: Low weight (≥20 to \<50 kg) patients: Starting dose 2.5 mg with optional titration to 5 and then 10 mg Mid weight (≥50 to \<80 kg) patients: Starting dose 5 mg with optional titration to 10 and then 20 mg High weight (≥80 to ≤150 kg) patients: Starting dose 10 mg with optional titration to 20 and then 40 mg |
| Low Dose Aliskiren | EXPERIMENTAL | Participants received body-weight stratified dose of aliskiren capsules (6.25/12.5/25 mg) once daily. Participants whose body weight ≥ 20 kilogram (kg) to less than \< 50 kg received 6.25 mg; ≥50 kg and \< 80 kg received 12.5 mg and ≥ 80 kg and ≤ 150 kg received 25 mg of aliskiren. |
| Mid dose | EXPERIMENTAL | Participants received body-weight stratified dose of aliskiren capsules (37.5/75/150 mg) once daily. Participants whose body weight ≥ 20 kg to \< 50 kg received 37.5 mg; ≥50 kg and \< 80 kg received 75 mg and ≥ 80 kg and ≤ 150 kg received 150 mg of aliskiren. |
| High dose | EXPERIMENTAL | Participants received body-weight stratified dose of aliskiren capsules (150/300/600 mg) once daily. Participants whose body weight ≥ 20 kg to \< 50 kg received 150 mg; ≥50 kg and \< 80 kg received 300 mg and ≥ 80 kg and ≤ 150 kg received 600 mg of aliskiren. |
| Non responder Olmesartan/Amlodipine | EXPERIMENTAL | Aliskiren/Amlodipine and Aliskiren/Amlodipine/HCTZ |
| Combination Aliskiren / Enalapril | EXPERIMENTAL | Aliskiren / Enalapril combination therapy-150 mg/10 mg titrated to 300 mg/ 10 mg film-coated tablets and administered orally. |
| 1 | PLACEBO_COMPARATOR | - |
| 2 | EXPERIMENTAL | Aliskiren 300 mg |
| Candesartan+HCTZ, aliskiren+HCTZ, aliskiren+HCTZ+amlodipine | EXPERIMENTAL | - |
| Aliskiren/amlodipine 300/10 mg tablet | EXPERIMENTAL | Aliskiren/amlodipine treatment regimen: At randomization, patients were treated with aliskiren/amlodipine 150/5 mg for one week. For the remaining 7 weeks of the study, patients were force-titrated to receive aliskiren/amlodipine 300/10 mg. |
| Amlodipine 10 mg capsule | ACTIVE_COMPARATOR | Amlodipine treatment regimen: At randomization, patients were treated with amlodipine 5 mg for one week. For the remaining 7 weeks of the study, patients were force-titrated to receive amlodipine 10 mg. |
| Aliskiren 300 mg/Amlodipine 5 mg | EXPERIMENTAL | Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks. |
| Aliskiren 300 mg/Amlodipine 10 mg | EXPERIMENTAL | Participants received 1 Aliskiren/Amlodipine 300/10 mg tablet + 1 Placebo to Aliskiren tablet orally once daily in the morning for 8 weeks. |
| Aliskiren 300 mg | ACTIVE_COMPARATOR | Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks. |
| Aliskiren 150 mg tablet | EXPERIMENTAL | Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos. |
| Aliskiren 300 mg tablet | EXPERIMENTAL | Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos. |
| Amlodipine 5 mg capsule | EXPERIMENTAL | Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos. |
| Aliskiren/amlodipine 150/5 mg tablet | EXPERIMENTAL | Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos. |
| Aliskiren/amlodipine 150/10 mg tablet | EXPERIMENTAL | 150/5 for 1 week, then up-titrated to 150/10 mg. Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos. |
| Aliskiren/amlodipine 300/5 mg tablet | EXPERIMENTAL | Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos. |
| Aliskiren / amlodipine | EXPERIMENTAL | Patients received an aliskiren 150 mg tablet plus an amlodipine 5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus amlodipine 10 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet and a placebo capsule. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed. |
| Aliskiren / hydrochlorothiazide | EXPERIMENTAL | Patients received an aliskiren 150 mg tablet plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo capsule and a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed. |
| Amlodipine / hydrochlorothiazide | EXPERIMENTAL | Patients received an amlodipine 5 mg capsule plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to amlodipine 10 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received 2 placebo tablets. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed. |
| Aliskiren / amlodipine / hydrochlorothiazide | EXPERIMENTAL | Patients received an aliskiren 150 mg tablet, a HCTZ 12.5 mg capsule and a placebo capsule for the first 3 days of treatment. Amlodipine 5 mg was then added for the remainder of the first 4 weeks of treatment. At the end of 4 weeks, patients were force titrated up to aliskiren / amlodipine / hydrochlorothiazide 300/10/25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed. |
| Aliskiren/Amlodipine/Hydrochlorothiazide | EXPERIMENTAL | Participants received aliskiren 300 milligrams (mg) plus hydrochlorothiazide 12.5 mg for one week, at Week 1 followed by combination of aliskiren 300 mg plus amlodipine 5 mg plus hydrochlorothiazide 12.5 mg for one week, at Week 2. Following Week 2, participants were force titrated up to aliskiren 300 mg plus amlodipine 10 mg plus hydrochlorothiazide 25 mg for 26 to 52 weeks (Weeks 28 to 54). All study medications were taken orally with water, once daily in the morning. |
| Aliskiren/hydrochlorothiazide (HCTZ) (300/25 mg) | EXPERIMENTAL | - |
| Aliskiren (300 mg) | ACTIVE_COMPARATOR | - |
| Aliskiren 75 mg | EXPERIMENTAL | - |
| Ramipril 5 mg | ACTIVE_COMPARATOR | Ramipril 5 mg once daily |
| Aliskiren/Amlodipine | EXPERIMENTAL | - |
| Aliskiren/Amlodipine/HCTZ | EXPERIMENTAL | - |
| Core Treatment | EXPERIMENTAL | Oral pills of aliskiren 150 mg /valsartan 160 mg in combination for 2-weeks. The aliskiren 300 mg /valsartan 320 mg in combination for 52-weeks, optional addition of Hydrochlorothiazide (HCTZ) 12.5 mg starting from Week 10 if the blood pressure was uncontrolled (mean sitting Systolic Blood Pressure ≥ 140 and/or mean sitting Diastolic Blood Pressure ≥ 90 mmHg). The dose of Hydrochlorothiazide (HCTZ) 12.5 mg could be increased to 25 mg if blood pressure remained uncontrolled. |
| Extension Treatment | EXPERIMENTAL | For patients entering into extension, those previously treated with Hydrochlorothiazide (HCTZ) 12.5 or 25 mg in addition to aliskiren 300 mg/valsartan 320 mg were treated with aliskiren 300 mg/valsartan 320 mg/HCTZ 25 mg in the extension. Those patients who had not received HCTZ during the core study were treated with aliskiren 300 mg/valsartan 320 mg/HCTZ 12.5 mg. The HCTZ 12.5 mg dose could be increased to HCTZ 25 mg if the mean sitting Systolic Blood Pressure (msSBP) was ≥140 mmHg and/or the mean sitting Diastolic Blood Pressure (msDBP) was ≥90 mmHg for 2 consecutive visits. |
| Aliskiren-based regimen | EXPERIMENTAL | Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg |
| Ramipril-based regimen | ACTIVE_COMPARATOR | Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg |
| 3 | EXPERIMENTAL | Various sequences of different doses of Aliskiren |
| 4 | EXPERIMENTAL | Various sequences of different doses of Aliskiren plus placebo |
| Furosemide 60 mg | EXPERIMENTAL | Treatment period 1 (Day 1 to Day 7): All eligible patients received 60 mg furosemide, 150 mg placebo of aliskiren, and 300 mg placebo aliskiren once daily. |
| Furosemide 60 mg + Aliskiren 150 mg | EXPERIMENTAL | Treatment Period 2 (Day 8 to day 17): Patients received 60 mg furosemide, 150 mg aliskiren and 300 mg placebo once daily. |
| Furosemide 60 mg + Aliskiren 300 mg | EXPERIMENTAL | Treatment Period 3 (Day 18 to day 27): Patients received 60 mg furosemide, 300 mg aliskiren and 150 mg placebo of aliskiren once daily. |
| Aliskiren and Valsartan | EXPERIMENTAL | - |
| Telmisartan and Ramipril | ACTIVE_COMPARATOR | - |
| Ramipril | EXPERIMENTAL | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received ramipril 10 mg capsule o.d and matching placebo of aliskiren tablet. |
| Aliskiren plus Ramipril | EXPERIMENTAL | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (period 2), patients received ramipril (10 mg once daily capsule) and aliskiren (150 mg once daily tablet) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site |
| Valsartan | ACTIVE_COMPARATOR | For the first week of the 8 week treatment period, patients received valsartan 160 mg, placebo to valsartan, and 2 tablets of placebo to aliskiren. For the remaining 7 weeks of the study, patients received valsartan 320 mg (two 160 mg capsules) and 2 tablets of placebo to aliskiren. The tablets and capsules (2 of each) were taken orally once daily each morning. To evaluate a missed dose, the last dose of medication was administered at the clinic, and the patient was scheduled to return 2 days later for exercise testing (8 weeks + 2 days). |
| Valsartan 320 mg | EXPERIMENTAL | Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. |
| Aliskiren/valsartan 300/320 mg | EXPERIMENTAL | Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study. |
| Fed Group | ACTIVE_COMPARATOR | - |
| Fasted group | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Aliskiren/Amlodipine 150/2.5 mg | DRUG | Aliskiren/amlodipine 150/2.5 mg tablet |
| Aliskiren/amlodipine 150/5 mg | DRUG | Aliskiren/amlodipine 150/5 mg tablet |
| Aliskiren 150 mg | DRUG | Aliskiren 150 mg tablet |
| Amlodipine 2.5 mg | DRUG | Amlodipine 2.5 mg capsule |
| Placebo of Aliskiren | DRUG | Aliskiren placebo tablet |
| Placebo of Amlodipine | DRUG | Amlodipine placebo capsule |
| Placebo of Aliskiren/amlodipine 150/2.5 mg | DRUG | Aliskiren/amlodipine 150/2.5 mg placebo tablet |
| Placebo of Aliskiren/amlodipine 150/5 mg | DRUG | Aliskiren/amlodipine 150/5 mg placebo tablet |
| Aliskiren | DRUG | Low weight patients: Starting dose 37.5 mg with optional titration to 75 and then 150 mg Mid weight patients: Starting dose 75 mg with optional titration to 150 and then 300 mg High weight patients: Starting dose 150 mg with optional titration to 300 and then 600 mg |
| Enalapril | DRUG | Low weight patients: Starting dose 2.5 mg with optional titration to 5 and then 10 mg Mid weight patients: Starting dose 5 mg with optional titration to 10 and then 20 mg High weight patients: Starting dose 10 mg with optional titration to 20 and then 40 mg |
| Aliskiren (6.25/12.5/25 mg) | DRUG | Aliskiren dispensing capsules containing minitablets (3.125 mg per minitablet). For the low dose arm, participants used one or more of the 6.25 mg capsule (containing 2 minitablets) once daily to reach the body-weight stratified dose of aliskiren. |
| Aliskiren (37.5/75/150 mg) | DRUG | Aliskiren dispensing capsules containing minitablets (3.125 mg per minitablet). For the medium dose arm, participants used one or more of the 37.5 mg capsule (containing 12 minitablets) once daily to reach the body- weight stratified dose of aliskiren. |
| Aliskiren (150/300/600 mg) | DRUG | Aliskiren dispensing capsules containing minitablets (3.125 mg per minitablet). For the high dose arm, participants used one or more of the 150 mg capsule (containing 48 minitablets) once daily to reach the body- weight stratified dose of aliskiren. |
| Aliskiren/Amlodipine and Aliskiren/Amlodipine/HCTZ | DRUG | Aliskiren 300 mg / Amlodipine 10 mg/HCTZ 12.5 mg |
| Placebo | DRUG | Placebo |
| Candesartan+HCTZ - Phase 1 | DRUG | 4 weeks treatment with candesartan 32 mg (two 16 mg tablets) plus hydrochlorothiazide 25 mg (two 12.5 mg tablets) taken orally with water in the morning between 7 and 10 am. |
| Aliskiren+HCTZ - Phase 2 | DRUG | Patients with uncontrolled mean sitting diastolic blood pressure (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am. |
| Aliskiren+HCTZ+amlodipine - Phase 3 | DRUG | The first 60 patients with uncontrolled mean sitting systolic or diastolic blood pressure (msDBP ≥ 90 mm Hg and/or msSBP ≥ 140 mm Hg) at the end of Phase 2 were offered 4 weeks treatment with aliskiren 300 mg plus HCTZ 25 mg in a single tablet plus an amlodipine 5 mg tablet taken orally with water in the morning between 7 and 10 am. |
| Aliskiren/amlodipine 300/10 mg tablet | DRUG | Each dose was taken by mouth with water at approximately 8:00 in the morning with or without food, except on the morning of the next office/clinic visit, when the medication was taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of two tablets and one capsule of study medication per day throughout the study. |
| Amlodipine 10 mg capsule | DRUG | Each dose was taken by mouth with water at approximately 8:00 in the morning with or without food, except on the morning of the next office/clinic visit, when the medication was taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of two tablets and one capsule of study medication per day throughout the study. |
| Aliskiren 300 mg | DRUG | Aliskiren 300 mg tablet taken orally once a day with a glass of water. |
| Aliskiren/Amlodipine 300/5 mg | DRUG | Aliskiren/Amlodipine 300/5 mg tablet taken orally once a day with a glass of water. |
| Aliskiren/Amlodipine 300/10 mg | DRUG | Aliskiren/Amlodipine 300/10 mg taken orally once a day with a glass of water. |
| Placebo to Aliskiren | DRUG | Placebo to Aliskiren tablet taken orally once a day. |
| Placebo to Aliskiren/Amlodipine | DRUG | Placebo to Aliskiren/Amlodipine taken orally once a day. |
| Aliskiren 150 mg tablet | DRUG | - |
| Aliskiren 300 mg tablet | DRUG | - |
| Amlodipine 5 mg capsule | DRUG | - |
| Aliskiren/amlodipine 150/5 mg tablet | DRUG | - |
| Aliskiren/amlodipine 150/10 mg tablet | DRUG | - |
| Aliskiren/amlodipine 300/5 mg tablet | DRUG | - |
| Amlodipine | DRUG | 5 and 10 mg capsules |
| Hydrochlorothiazide (HCTZ) | DRUG | 12.5 and 25 mg capsules |
| Hydrochlorothiazide | DRUG | 12.5 mg and 25 mg capsule |
| Aliskiren/hydrochlorothiazide (HCTZ) (300/25 mg) | DRUG | During the titration period, patients received aliskiren/hydrochlorothiazide (HCTZ) 150/12.5 mg for 1 week. |
| Aliskiren (300 mg) | DRUG | During the titration period, patients received aliskiren 150 mg for one week. Subsequently, patients were up-titrated and received aliskiren 300 mg. |
| Aliskiren 75 mg | DRUG | Aliskiren 75 mg tablet taken once daily in the morning with a light meal. |
| Ramipril | DRUG | comparator |
| Valsartan | DRUG | Valsartan 320 mg |
| Aliskiren/HCTZ | DRUG | - |
| Aliskiren plus placebo | DRUG | - |
| Furosemide 60 mg | DRUG | Furosemide 60 mg commercially-available tablets |
| Placebo for Aliskiren | DRUG | Matching placebo for aliskiren 150 mg and 300 mg |
| Aliskiren/ Valsartan | DRUG | - |
| Telmisartan/ Ramipril | DRUG | - |
| Placebo to ramipril | DRUG | Matching placebo to ramipril capsule in double blind phase |
| Placebo to valsartan | DRUG | Placebo to valsartan was supplied in capsules matching valsartan 160 mg. |
| Placebo Aliskiren | DRUG | Placebo Aliskiren taken orally once daily. |
| Placebo Amlodipine | DRUG | Placebo Amlodipine taken orally once daily |
| Valsartan 320 mg | DRUG | Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. If a patient was not up-titrated or required down-titration, the patient continued on that dose for the remainder of the study. If 2 down-titrations were required, they stopped study drug. In order to adequately blind the study, patients were required to take 1 tablet and 2 capsules during the first 4 weeks of the study and 2 tablets and 2 capsules for the remainder of the study. Each dose was taken by mouth with water at approximately 8:00 AM. |
| Aliskiren/valsartan 300/320 mg | DRUG | Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study. If a patient was not up-titrated or required down-titration, the patient continued on that dose for the remainder of the study. If 2 down-titrations were required, they stopped study drug. In order to adequately blind the study, patients were required to take 1 tablet and 2 capsules during the first 4 weeks of the study and 2 tablets and 2 capsules for the remainder of the study. Each dose was taken by mouth with water at approximately 8:00 AM. |
| SPP100 | DRUG | - |
| SPP100 (aliskiren) | DRUG | - |
Inclusion Criteria: * Patients with essential hypertension (msDBP ≥ 95 mmHg and \< 110 mmHg and msSBP ≥140 mmHg ) * Outpatients Exclusion Criteria: * Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg) * History of allergy or hypersensitivity to renin inhibitors, calcium channel blocker...
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SPP100 is being developed for the treatment of hypertension, also known as high blood pressure. It is a small molecule cardiovascular therapy studied in patients with mild to moderate essential hypertension. Development has reached Phase 2, and the program includes two completed clinical trials with a combined enrollment of 334 patients.
SPP100 is being developed by Novartis AG, which trades under the ticker NVS. Novartis is the sponsor behind the clinical program evaluating the drug in hypertension. The program includes two completed trials, one conducted in Japan and one in Switzerland.
SPP100 is in Phase 2 development for hypertension. It is an investigational small molecule and is not approved. Two trials have been completed, including a Phase 2 long term study of SPP100 in patients with essential hypertension and a Phase 1 pharmacokinetic and pharmacodynamic study in Japanese patients.
Two completed trials have evaluated SPP100. NCT00246584 was a Phase 2 long term study in patients with essential hypertension conducted in Switzerland, enrolling 300 patients. NCT00424541 was a Phase 1 pharmacokinetic and pharmacodynamic study in Japanese patients with mild to moderate essential hypertension, enrolling 34 patients in Japan.
Yes, SPP100 is also known as aliskiren. Both names refer to the same investigational small molecule developed by Novartis for hypertension. Readers searching for either name will find the same Phase 2 program, which includes the completed trials NCT00246584 and NCT00424541.
The SPP100 clinical program enrolled a total of 334 patients across two completed trials. The Phase 2 long term hypertension study NCT00246584 enrolled 300 patients, and the Phase 1 study NCT00424541 in Japanese patients enrolled 34. Both trials were randomized and double blind.