Hypertension
Conditions
Brief summary
This study will explore the dose-response of losartan as well as the safety and tolerability in children from 6 months to 6 years of age.
Interventions
DRUGlosartan potassium
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.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 6 Years
Healthy volunteers
No
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 taking hypertensive medications within the past 30 days * Participant has a known sensitivity to losartan or history of angioneurotic edema
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Systolic Blood Pressure | Baseline and Day 21 | 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 Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | up to 12 weeks (Base Study); up to 24 months (Extension) | — |
| Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | up to 12 weeks (Base Study); up to 24 months (Extension) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Diastolic Blood Pressure | Baseline and Day 21 | Sitting 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. Diastolic BP was determined by averaging 3 replicate measurements obtained at least 1 minute apart. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Losartan Potassium 0.1 to 1.4 mg/kg 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 | 33 |
| Losartan Potassium 0.3 to 1.4 mg/kg 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 | 34 |
| Losartan Potassium 0.7 to 1.4 mg/kg Open-label losartan at starting dose of 0.7 mg/kg/day with uptitration at Week 3, 6, or 9 to the next highest dose level if blood pressure goal not achieved | 34 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 12-week Base Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| 12-week Base Study | Protocol-specific Criteria Met | 1 | 0 | 1 | 0 |
| 12-week Base Study | Protocol Violation | 0 | 0 | 1 | 0 |
| Optional Extension | Adverse Event | 0 | 0 | 0 | 1 |
| Optional Extension | End of Study | 0 | 0 | 0 | 11 |
| Optional Extension | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Optional Extension | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Optional Extension | Physician Decision | 0 | 0 | 0 | 3 |
| Optional Extension | Protocol-specific criteria met | 0 | 0 | 0 | 9 |
| Optional Extension | Protocol Violation | 0 | 0 | 0 | 1 |
| Optional Extension | Withdrawal by Subject | 0 | 0 | 0 | 10 |
Baseline characteristics
| Characteristic | Losartan Potassium 0.1 to 1.4 mg/kg | Losartan Potassium 0.3 to 1.4 mg/kg | Losartan Potassium 0.7 to 1.4 mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 40.2 Months STANDARD_DEVIATION 24.4 | 45.0 Months STANDARD_DEVIATION 21.5 | 40.6 Months STANDARD_DEVIATION 21.2 | 42.0 Months STANDARD_DEVIATION 22.3 |
| Sex: Female, Male Female | 13 Participants | 16 Participants | 14 Participants | 43 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 20 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 34 | 22 / 54 | 23 / 63 | 17 / 33 | 12 / 15 | 20 / 28 | 20 / 31 | 28 / 42 |
| serious Total, serious adverse events | 3 / 34 | 2 / 54 | 2 / 63 | 0 / 33 | 3 / 15 | 5 / 28 | 2 / 31 | 5 / 42 |
Outcome results
Primary
Mean Change From Baseline in Systolic Blood Pressure
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.
Time frame: Baseline and Day 21
Population: Analysis performed using the Full Analysis Set defined as all randomized participants who had at least 1 dose of study drug, had baseline data, and had a post-treatment endpoint observation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium 0.1 to 1.4 mg/kg | Mean Change From Baseline in Systolic Blood Pressure | -7.31 mmHg | Standard Deviation 12.53 |
| Losartan Potassium 0.3 to 1.4 mg/kg | Mean Change From Baseline in Systolic Blood Pressure | -7.65 mmHg | Standard Deviation 7.49 |
| Losartan Potassium 0.7 to 1.4 mg/kg | Mean Change From Baseline in Systolic Blood Pressure | -6.67 mmHg | Standard Deviation 7.86 |
p-value: 0.75395% CI: [-6.45, 8.9]ANCOVA
Primary
Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s)
Time frame: up to 12 weeks (Base Study); up to 24 months (Extension)
Population: All Patients as Treated Population, which consisted of all randomized participants who received at least 1 dose of study drug. Adverse events for the base study were reported by the dose taken at the time of the event and not the study group to which they were randomly assigned. Adverse events for the study extension were reported as 1 arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan Potassium 0.1 to 1.4 mg/kg | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Clinical Adverse Event | 21 Participants |
| Losartan Potassium 0.1 to 1.4 mg/kg | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Laboratory Adverse Event | 1 Participants |
| Losartan Potassium 0.3 to 1.4 mg/kg | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Clinical Adverse Event | 30 Participants |
| Losartan Potassium 0.3 to 1.4 mg/kg | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Laboratory Adverse Event | 1 Participants |
| Losartan Potassium 0.7 to 1.4 mg/kg | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Clinical Adverse Event | 36 Participants |
| Losartan Potassium 0.7 to 1.4 mg/kg | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Laboratory Adverse Event | 0 Participants |
| Base Study-Losartan Potassium 1.4 mg/kg | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Laboratory Adverse Event | 0 Participants |
| Base Study-Losartan Potassium 1.4 mg/kg | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Clinical Adverse Event | 22 Participants |
| Extension-Losartan Potassium | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Clinical Adverse Event | 75 Participants |
| Extension-Losartan Potassium | Number of Participants Who Reported 1 or More Clinical and/or Laboratory Adverse Event(s) | Laboratory Adverse Event | 5 Participants |
Primary
Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event
Time frame: up to 12 weeks (Base Study); up to 24 months (Extension)
Population: All Patients as Treated Population, which consisted of all randomized participants who received at least 1 dose of study drug. Adverse events for the base study were reported by the dose taken at the time of the event and not the study group to which they were randomly assigned. Adverse events for the study extension were reported as 1 arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan Potassium 0.1 to 1.4 mg/kg | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Clinical Adverse Event | 0 Participants |
| Losartan Potassium 0.1 to 1.4 mg/kg | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Laboratory Adverse Event | 0 Participants |
| Losartan Potassium 0.3 to 1.4 mg/kg | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Clinical Adverse Event | 0 Participants |
| Losartan Potassium 0.3 to 1.4 mg/kg | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Laboratory Adverse Event | 0 Participants |
| Losartan Potassium 0.7 to 1.4 mg/kg | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Clinical Adverse Event | 0 Participants |
| Losartan Potassium 0.7 to 1.4 mg/kg | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Laboratory Adverse Event | 0 Participants |
| Base Study-Losartan Potassium 1.4 mg/kg | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Laboratory Adverse Event | 0 Participants |
| Base Study-Losartan Potassium 1.4 mg/kg | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Clinical Adverse Event | 0 Participants |
| Extension-Losartan Potassium | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Clinical Adverse Event | 1 Participants |
| Extension-Losartan Potassium | Number of Participants Who Were Discontinued From Study Due to a Clinical and/or Laboratory Adverse Event | Laboratory Adverse Event | 0 Participants |
Secondary
Mean Change From Baseline in Diastolic Blood Pressure
Sitting 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. Diastolic BP was determined by averaging 3 replicate measurements obtained at least 1 minute apart.
Time frame: Baseline and Day 21
Population: Analysis performed using the Full Analysis Set defined as all randomized participants who had at least 1 dose of study drug, had baseline data, and had a post-treatment endpoint observation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan Potassium 0.1 to 1.4 mg/kg | Mean Change From Baseline in Diastolic Blood Pressure | -8.25 mmHg | Standard Deviation 11.76 |
| Losartan Potassium 0.3 to 1.4 mg/kg | Mean Change From Baseline in Diastolic Blood Pressure | -5.15 mmHg | Standard Deviation 8.06 |
| Losartan Potassium 0.7 to 1.4 mg/kg | Mean Change From Baseline in Diastolic Blood Pressure | -6.73 mmHg | Standard Deviation 8.59 |
p-value: 0.64395% CI: [-5.9, 9.51]ANCOVA