Efficacy of Losartan + Amlodipine Compared to Amlodipine Alone in the Treatment of Uncontrolled High Blood Pressure (MK-0954F-399)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01277822
First received: January 13, 2011
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

This study will determine whether using losartan and amlodipine together will be non-inferior in lowering blood pressure than amlodipine alone.


Condition Intervention Phase
Hypertension
Drug: Losartan (+) amlodipine
Drug: Placebo to match losartan/amlodipine tablets
Drug: Amlodipine camsylate
Drug: Placebo to match amlodipine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The 8 Weeks, Multicenter, Randomized, Double-blind, Clinical Study To Evaluate Efficacy Of Treatment With Losartan/Amlodipine 100/5 mg Combination Compared To Amlodipine 10 mg Monotherapy In Hypertensive Patients Who Are Not Appropriately Respond To Amlodipine 5 mg Monotherapy

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Diastolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.


Secondary Outcome Measures:
  • Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    Diastolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.

  • Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Systolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.

  • Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    Systolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.

  • Percentage of Participants Who Achieve Target Blood Pressure at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Participants were evaluated at Week 8 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) <90mmHg or sitting systolic BP (sitSBP) <140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline.

  • Percentage of Participants Who Achieve Target Blood Pressure at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Participants were evaluated at Week 4 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) <90mmHg or sitting systolic BP (sitSBP) <140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline.

  • Percentage of Participants Who Had Peripheral Edema During the Study [ Time Frame: up to 8 weeks ] [ Designated as safety issue: Yes ]
    A pitting assessment of edema on both legs was performed at baseline and throughout the study. Participants were assessed in a seated position with both feet extended and the right ankle in a neutral dorsiflexion position. The index finger was pressed firmly over the bony prominence approximately 3cm proximal to the midpoint of the medial malleolus of the right ankle and will be held for three seconds. Presence of a residual indentation in the area after releasing pressure on the index finger was considered positive for pitting edema.

  • Change From Baseline in Ankle Circumference at Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: Yes ]
    Each ankle was marked with a semi-permanent marker at approximately 3 cm proximal to the midpoint of the medial malleolus to aid consistency in the performance of the measurements. Ankle circumference was measured in both ankles at baseline and Week 8 using a tension controlled tape to minimize error.


Enrollment: 334
Study Start Date: May 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Losartan/amlodipine Treatment Arm
One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.
Drug: Losartan (+) amlodipine
One tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks.
Other Name: COZAAR XQ™
Drug: Placebo to match amlodipine
2 tablets containing placebo, orally, once daily, for 8 weeks.
Active Comparator: Amlodipine Treatment Arm
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.
Drug: Placebo to match losartan/amlodipine tablets
One tablet containing placebo, orally, once daily, for 8 weeks.
Drug: Amlodipine camsylate
2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Participants with essential hypertension:

    • who are on single drug therapy
    • who are newly diagnosed and not yet taking any drug therapy, or have not had any drug therapy for at least 2 weeks prior to entering study
    • who have blood pressure readings of 90mmHg ≤ MSDBP < 110mmHg and 140mmHg ≤ MSSBP <180mmHg after 2 weeks wash-out for patients on single agent.
  • Randomization (Visit 3)

    • After dosing of amlodipine 5mg for 6 weeks, blood pressure readings are:

      • 90mmHg ≤ MSDBP < 110mmHg and 140mmHg ≤ MSSBP < 180mmHg.

Exclusion criteria

  • Participant with MSDBP ≥ 110mmHg or MSSBP ≥ 180mmHg.
  • Participant currently taking ≥ 2 antihypertensive medications (note: fixed-dose combination medicine should be counted as the number of active ingredients).
  • Participant with known secondary hypertension of any etiology.
  • Participant with malignant hypertension or current evidence of impending or active malignant hypertension, including headache, papilledema, cardiac ischemia, or pulmonary congestion precipitated by elevated blood pressure.
  • Participant with known intolerance, contraindication or hypersensitivity to any component of dihydropyridines, angiotensin II receptor blockers.
  • Participant showing positive in pregnancy test, lactating woman, or woman who intends to get pregnant during the study period.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01277822     History of Changes
Other Study ID Numbers: 0954F-399
Study First Received: January 13, 2011
Results First Received: March 24, 2014
Last Updated: May 19, 2014
Health Authority: Korea: Institutional Review Board

Keywords provided by Merck Sharp & Dohme Corp.:
Hypertension
Uncontrolled hypertension
High blood pressure
Uncontrolled high blood pressure
Untreated high blood pressure
Untreated hypertension
Essential hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Losartan
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Antihypertensive Agents
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 23, 2014