Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as losartan potassium, Losartan Potassium
losartan · 6 trials · 3 indications
Sitting blood pressure (\[BP\] or supine if child could not sit) was measured after the participant had been seated for 5 minutes with back supported, feet on the floor and right arm (or left arm if it was the customary side for BP measurement for the patient) supported at heart level. Systolic BP was determined by averaging 3 replicate measurements obtained at least 1 minute apart.
Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 14 weeks of treatment
Change in urinary protein excretion, determined as urinary Pr/Cr ratio compared to baseline\*, after approximately twelve weeks of treatment. Baseline is defined as values obtained at Visit 3, Week (-1) during the Single Blind Run-in period.
Change in urinary protein excretion, determined as urinary Pr/Cr ratio compared to baseline\*, after approximately three years of treatment. \*The baseline for efficacy data in the extension was defined as the last value obtained in the double-blind treatment phase.
The outcome measure of glomerular filtration rate was based on mL/min/1.73m\^2, as determined by the Schwartz formula: GFR = \_\_\_\_\_0.55 x height (cm)\_\_\_\_\_\_\_ divided by serum creatinine (mg/dL) GFR values were compared to the baseline GFR measure. \[Note: For male participants, ages 13 to 17 years, 0.70 was used as the multiplier in place of 0.55\] Baseline in regard to the extension is defined as the last value obtained in the double-blind treatment phase.
Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 8. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 8. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 12. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 12. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 16. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 16. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
The augmentation index (AIx) is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. A mathematical transfer function translated the peripheral wave form into a central waveform using an FDA approved process based on directly recorded arterial pressure values. The mean AIx for each subject was estimated as a time-weighted average over the 10-hour post dose observation period and expressed as a change from baseline.
The augmentation index (AIx) is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. A mathematical transfer function translated the peripheral wave form into a central waveform using an FDA approved process based on directly recorded arterial pressure values. The mean AIx for each subject was estimated as a time-weighted average over the 10-hour post dose observation period and expressed as a change from baseline.
| Arm | Type | Description |
|---|---|---|
| Losartan potassium 0.1 to 1.4 mg/kg | EXPERIMENTAL | Open-label losartan at starting dose of 0.1 mg/kg/day with uptitration at Weeks 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved |
| Losartan potassium 0.3 to 1.4 mg/kg | EXPERIMENTAL | Open-label losartan at starting dose of 0.3 mg/kg/day with uptitration at Weeks 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved |
| Losartan potassium 0.7 to 1.4 mg/kg | EXPERIMENTAL | Open-label losartan at starting dose of 0.7 mg/kg/day with uptitration at Weeks 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved |
| Losartan-Based Regimen Alone (L Group) | ACTIVE_COMPARATOR | Losartan-based regimen, with sequential titration including HCTZ and CCB as needed to achieve target blood pressure. |
| Diet Management and Losartan-Based Regimen (DML Group) | EXPERIMENTAL | Losartan with sequential titration including HCTZ and CCB as needed to achieve target blood pressure combined with low-salt intake diet. |
| Losartan Double-Blind Base Study (12-weeks) | EXPERIMENTAL | Normotensive participants received losartan. Hypertensive participants received either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo). |
| Amlodipine Double-Blind Base Study (12-weeks) | ACTIVE_COMPARATOR | Hypertensive participants were randomized to receive either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo) for 12 weeks. |
| Losartan Open-Label Extension Phase (Month 36) | EXPERIMENTAL | Participants were were carried over from the base study into the long-term safety extension. Participants in the extension were randomly assigned to either losartan or enalapril regardless of their previous randomized treatment. Dosing during the extension period (i.e. starting dose and any titration) was up to the investigator and varied by patient). |
| Enalapril Open-Label Extension Phase (Month 36) | ACTIVE_COMPARATOR | Participants were were carried over from the base study into the long-term safety extension. Participants in the extension were randomly assigned to either losartan or enalapril regardless of their previous randomized treatment. Dosing during the extension period (i.e. starting dose and any titration) was up to the investigator and varied by patient). |
| 1 | EXPERIMENTAL | Losartan |
| 2 | PLACEBO_COMPARATOR | Placebo |
| Losartan 50 mg | EXPERIMENTAL | 50-mg losartan tablet administered daily with 1 tablet of 100-mg losartan placebo beginning Week 1 and continuing to end of study (up to 4 years) |
| Losartan 150 mg | EXPERIMENTAL | Titrated losartan administration up to daily 150-mg losartan: Week 1, daily 50-mg losartan tablet coadministered with 100-mg losartan placebo; Week 2, daily 50-mg losartan placebo coadministered with 100-mg losartan; Week 3 to end of study (up to 4 years), daily 50-mg losartan tablet coadministered with 100-mg losartan |
| 3 | ACTIVE_COMPARATOR | losartan 100 mg + ISMN 15 mg |
| 4 | ACTIVE_COMPARATOR | losartan 100 mg + ISMN 60 mg |
| 5 | PLACEBO_COMPARATOR | Placebo |
| Name | Type | Description |
|---|---|---|
| losartan potassium | DRUG | losartan potassium, dry powder, to be suspended in liquid and given orally, once daily; doses will start at 0.1 mg/kg, 0.3 mg/kg, and 0.7 mg/kg, respectively, in the three study arms and can be escalated up to 1.4 mg/kg (maximum dose 100 mg) until target blood pressure is reached. |
| losartan potassium (+ hydrochlorothiazide [HCTZ] + calcium channel blocker [CCB]) | DRUG | Losartan 50 mg or 100 mg once daily for 40 weeks with sequential titration including HCTZ 12.5 mg or 25 mg and CCB only as needed to achieve target blood pressure, as follows: Patients with mild-moderate hypertension, uncontrolled hypertension on monotherapy, or diabetes: * Losartan 50 mg * Losartan 100 mg * Losartan 100 mg/HCTZ 12.5 mg * Losartan 100 mg/HCTZ 25 mg * Losartan 100 mg/HCTZ 25 mg + CCB Patients with severe hypertension: * Losartan 50 mg/HCTZ 12.5 mg * Losartan 100 mg/HCTZ 12.5 mg * Losartan 100 mg/HCTZ 25 mg * Losartan 100 mg/HCTZ 25 mg + CCB * Losartan 100 mg/HCTZ 25 mg + increasing CCB |
| Low Salt Diet | BEHAVIORAL | Low-salt intake diet (Dietary Approaches to Stop Hypertension \[DASH\]) including: * Healthy diet * Reduction in sodium intake to less than 2300 mmol/day * Low alcohol consumption (less than 2 standard drinks/day) |
| Comparator: Placebo (Losartan) | OTHER | Placebo (losartan suspension), administered orally, once daily for 12 weeks |
| Comparator: amlodipine besylate | DRUG | Amlodipine besylate (1 mg/mL) liquid suspension, oral administration, titrated to 0.2 mg/kg/day (5 mg maximum dose) per day for 12 Weeks |
| Comparator: Placebo (amlodipine besylate) | OTHER | Liquid suspension, 1mg/mL, titrated to 0.2 mg/kg/day (5 mg maximum dose) once daily, for 12 weeks |
| Placebo (Losartan) | OTHER | Normotensive patients randomized to losartan placebo for 12 weeks. |
| Enalapril Maleate | DRUG | Enalapril 2.5-, 5-, 10-, and 20-mg tablets or enalapril suspension (1 mg/mL), oral administration, once daily for 36 months. |
| Comparator: losartan +/- HCTZ | DRUG | Placebo to losartan once daily for 4 weeks in run-in period. Then, losartan 50 mg for 4 weeks, then titrate to losartan 100 mg at Week 4, then titrate to losartan 100 mg + hydrochlorothiazide (HCTZ) 12.5 mg at Week 8, and finally titrate to losartan 100 mg + HCTZ 25 mg at Week 12. Duration of treatment is approximately 16 weeks. |
| Comparator: Placebo | DRUG | Placebo to losartan once daily for 4 weeks in run-in period. Then, placebo to losartan or losartan/HCTZ once daily for approximately 16 weeks. |
| Losartan 50 mg | DRUG | 50-mg losartan oral tablet |
| Losartan 150 mg | DRUG | 100-mg losartan oral tablet + 50-mg losartan oral tablet |
| Comparator: isosorbide mononitrate (ISMN) | DRUG | Single dose ISMN 60 mg in one of five treatment periods |
| Comparator: losartan + ISMN | DRUG | Single dose losartan 100 mg and ISMN 15 mg in one of five treatment periods |
Inclusion Criteria: * Participant is determined to be hypertensive Exclusion Criteria: * Participant has a history of severe or symptomatic hypertension * Participant has history of heart failure, rhythm disturbance or cardiomyopathy, or obstructive valvular disease * Participant has started taki...
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