A Study to Investigate the Magnitude and Duration of Response of MK0954 Compared to Placebo in Patients With Hypertension (0954-021)(COMPLETED)

A Double-blind, Randomized, Parallel-group, Placebo-controlled Pilot Study to Investigate the Magnitude and Duration of Response and the Safety of MK0954 (50 mg Given Once or Twice Daily, or 100 mg Given Once Daily) Compared to Placebo Using Ambulatory Blood Pressure Monitoring

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00886600

Enrollment

122

Registered

2009-04-23

Start date

1991-05-31

Completion date

1992-08-31

Last updated

2015-08-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypertension

Brief summary

The purpose of this study was to evaluate the magnitude and durations of the antihypertensive effects of losartan using ambulatory blood pressure monitoring (ABPM), and to evaluate the safety of losartan 50 and 100 mg doses compared to placebo.

Interventions

DRUGlosartan potassium

losartan potassium (50 or 100 mg) administered orally once daily (q.d.)or twice daily (b.i.d) for four weeks

DRUGComparator: placebo

placebo capsules to losartan potassium (50 or 100 mg) administered orally once daily (q.d.)or twice daily (b.i.d) for four weeks

DRUGhydrochlorothiazide (HCTZ)

open-label hydrochlorothiazide (HCTZ) 12.5 mg (for patients with Sitting Diastolic Blood Pressure (SiDBP) ≥85 mm Hg after 4 weeks of losartan monotherapy (Combination Therapy Period)) orally once daily (q.d.) for 2 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

21 Years to No maximum

Healthy volunteers

Inclusion criteria

* Non-black men and women with mild to moderate hypertension and within 30% of their ideal body weight * Patient is in good general health * Blood pressure at time of randomization is 95-115 mm Hg

Exclusion criteria

* Secondary Hypertension or history of malignant hypertension * History of stroke * History of myocardial infarction * Atrial flutter or atrial fibrillation * History of congestive Heart failure * Patient taking major psychotropic agent or anti-depressant * Patient regularly uses NSAIDS or high dose aspirin * Known positive test for HIV/AIDS or Hepatitis B * Patient is being treated for acute ulcer disease * Prior exposure to losartan * Actively treated diabetes mellitus * History of chronic liver disease * Actively treated diabetes mellitus * Any known bleeding or platelet disorder * Absence of one kidney * Women of childbearing potential * Alcoholism or drug addiction

Design outcomes

Primary

Measure	Time frame
Mean Change From Baseline in 24-hour Diastolic Ambulatory Blood Pressure Monitoring (ABPM) at Week 4	24 hour period at Baseline and Week 4
Mean Change From Baseline in 24-hour Systolic Ambulatory Blood Pressure Monitoring (ABPM) at Week 4	24-hour period at baseline and Week 4

Secondary

Measure	Time frame
Mean Change From Baseline in Sitting Diastolic Blood Pressure (siDBP) 24 Hours After Morning Dose at Week 4	Baseline and 24-hours after morning dose at Week 4
Mean Change From Baseline in Sitting Diastolic Blood Pressure (siDBP) After Adding HCTZ 24 Hours After Morning Dose at Week 6	Baseline and 24-hours after morning dose at Week 6
Mean Change From Week 4 in Sitting Diastolic Blood Pressure (siDBP) Adding HCTZ 24 Hours After Morning Dose at Week 6	Baseline and 24-hours after morning dose at Week 6

Participant flow

Recruitment details

Patients were recruited at 9 sites in the United States. Prime Therapy Period: May, 1991 to March, 1992.

Pre-assignment details

Patients could be randomized if sitting diastolic blood pressure (SiDBP) after 2 and 4 weeks of placebo washout was 95-115 mm Hg and the difference between measurements at the 2 visits was ≤7 mm Hg. At the end of placebo baseline the mean 24-hr DBP using ambulatory blood pressure monitoring (ABPM) had to be at least 85 mm Hg.

Participants by arm

Arm	Count
Placebo / HCTZ 12.5 mg Losartan placebo orally once daily for 4 weeks followed by Losartan placebo + open-label hydrochlorothiazide (HCTZ) 12.5 mg (for patients with SiDBP ≥85 mm Hg) orally once daily for 2 weeks	32
Losartan 50 mg q.d. / HCTZ 12.5 mg Losartan 50 mg orally once daily for 4 weeks followed by Losartan 50 mg + open-label HCTZ 12.5 mg (for patients with SiDBP ≥85 mm Hg) orally once daily for 2 weeks	29
Losartan 100 mg q.d. / HCTZ 12.5 mg Losartan 100 mg orally once daily for 4 weeks followed by Losartan 100 mg once daily + open-label HCTZ 12.5 mg (for patients with SiDBP ≥85 mm Hg).orally once daily for 2 weeks	30
Losartan 50 mg b.i.d. / HCTZ 12.5 mg Losartan 50 mg orally twice daily for 4 weeks followed by Losartan 50 mg twice daily + open-label HCTZ 12.5 mg (for patients with SiDBP ≥85 mm Hg) orally once daily for 2 weeks	31
Total	122

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Combination Therapy Period	Adverse Event	0	0	1	0
Combination Therapy Period	Protocol Violation	0	0	1	0
Double-blind Monotherapy	Adverse Event	1	1	1	1
Double-blind Monotherapy	Protocol Violation	0	0	0	1
Double-blind Monotherapy	Withdrawal by Subject	1	0	0	0

Baseline characteristics

Characteristic	Placebo / HCTZ 12.5 mg	Losartan 50 mg q.d. / HCTZ 12.5 mg	Losartan 100 mg q.d. / HCTZ 12.5 mg	Losartan 50 mg b.i.d. / HCTZ 12.5 mg	Total
Age, Continuous	52.2 years STANDARD_DEVIATION 12	56.8 years STANDARD_DEVIATION 12.1	51.2 years STANDARD_DEVIATION 9.6	54.1 years STANDARD_DEVIATION 9	53.5 years STANDARD_DEVIATION 10.8
Diastolic 24-hr mean ambulatory blood pressure monitoring (ABPM)	94.8 mm Hg STANDARD_DEVIATION 5.9	94.0 mm Hg STANDARD_DEVIATION 6.9	93.8 mm Hg STANDARD_DEVIATION 6	94.4 mm Hg STANDARD_DEVIATION 6.9	94.2 mm Hg STANDARD_DEVIATION 6.4
Race/Ethnicity Caucasian	30 participants	29 participants	30 participants	30 participants	119 participants
Race/Ethnicity Filipino	1 participants	0 participants	0 participants	0 participants	1 participants
Race/Ethnicity Indian	1 participants	0 participants	0 participants	0 participants	1 participants
Race/Ethnicity Oriental	0 participants	0 participants	0 participants	1 participants	1 participants
Sex: Female, Male Female	7 Participants	10 Participants	9 Participants	13 Participants	39 Participants
Sex: Female, Male Male	25 Participants	19 Participants	21 Participants	18 Participants	83 Participants
Sitting Diastolic Blood Pressure (SiDBP)	100.7 mm Hg STANDARD_DEVIATION 4	100.0 mm Hg STANDARD_DEVIATION 4.6	101.5 mm Hg STANDARD_DEVIATION 5.1	101.2 mm Hg STANDARD_DEVIATION 4.8	100.9 mm Hg STANDARD_DEVIATION 4.6