LAAS (Losartan Anti-Atherosclerosis Study)(0954-330)(COMPLETED)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00496834
• Collaborator: (none)
• Enrollment: 201
• Arms: 2
• Actual Duration (Months): 19

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate efficacy, arterial stiffness measured by Pulse Wave Velocity (PWV) of Losartan potassium group compared to Carvedilol group after 24 weeks of treatment in patients with the essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: losartan potassium; Drug: Comparator: carvedilol; Drug: Comparator: losartan (+) hydrochlorothiazide (HCTZ); Drug: Comparator: carvedilol (+) hydrochlorothiazide	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 201 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Comparative, Non-inferiority, Multicenter Study to Compare Efficacy of Losartan Potassium Group and Carvedilol Group on Arterial Stiffness in Essential Hypertension Patients
• Actual Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Losartan or Losartan/HCTZ	Drug: losartan potassium; Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg/ hydrochlorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan); Drug: Comparator: losartan (+) hydrochlorothiazide (HCTZ); Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg/ hydrochlorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan)
Active Comparator: 2 Carvedilol or Carvedilol/HCTZ	Drug: Comparator: carvedilol; Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan); Drug: Comparator: carvedilol (+) hydrochlorothiazide; Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan)

Outcome Measures

Primary Outcome Measures

1. Pulse Wave Velocity (PWV) Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug [Baseline and 24 Weeks]

   Analysis was performed in the modified intention to treat (mITT) population.

2. PWV Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug [Baseline and 24 Weeks]

   Analysis was performed in the per protocol (PP) population which additionally excludes certain protocol violations as described in the analysis plan.

Secondary Outcome Measures

1. Systolic Blood Pressure (SBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug [Baseline and 24 weeks]

2. Diastolic Blood Pressure (DBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug [Baseline and 24 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or Female adults, 18 years or over

• Essential Hypertension with mean SBP (systolic blood pressure) ≥ 140 mm Hg or mean DBP (diastolic blood pressure) ≥ 90 mm Hg* when blood pressure is measured at Visit 1(week -2) and at Visit 2(week 0).

If diabetes patients, mean SBP ≥ 130 mm Hg or mean DBP ≥ 80 mm Hg (Mean of blood pressure values measured consecutively at least 2 minutes apart)

• Patient who is willing to, and is able to sign the informed consent form

Exclusion Criteria:

• Patient Is Pregnant Or Breastfeeding, Or Expecting To Conceive Within The Projected Duration Of The Study

• Patient Has Known Or Suspected Secondary Hypertension Of Any Etiology

• Patient has history of malignant hypertension

• Patient has history of cerebrovascular accident (cerebral infarction) or myocardiac infarction within the last 6 months

• Patient takes antihypertensive drugs

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00496834
• Other Study ID Numbers: 0954-330; 2007_015; NCT01001416
• First Posted: Jul 4, 2007
• Last Update Posted: Feb 22, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hypertension; Losartan; Hydrochlorothiazide; Carvedilol

Study Results

Participant Flow

Recruitment Details	7 centers participated in this study (7 medical centers of university). FPE (First patient enrolled): Feb-2008, FPI (First patient in): Feb-2008, LPO (Last patient out): Sep-2009

Arm/Group Title	Losartan	Carvedilol
Arm/Group Description	Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).	Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).
Period Title: Overall Study
STARTED	101	100
COMPLETED	83	87
NOT COMPLETED	18	13

Baseline Characteristics

Arm/Group Title	Losartan	Carvedilol	Total
Arm/Group Description	Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).	Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).	Total of all reporting groups
Overall Participants	101	100	201
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.0 (9.3)	50.1 (10.2)	49.6 (9.7)
Age, Customized (participants) [Number]
>= 18 to < 65 years	96 95%	91 91%	187 93%
>=65 years	5 5%	9 9%	14 7%
Sex: Female, Male (Count of Participants)
Female	63 62.4%	57 57%	120 59.7%
Male	38 37.6%	43 43%	81 40.3%
DBP (diastolic blood pressure) (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	96.4 (8.8)	96.4 (8.3)	96.4 (8.5)
Height (Centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeters]	164.9 (7.8)	163.3 (9.2)	164.1 (8.5)
PWV (pulse wave velocity) (meters/second) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters/second]	7.6 (1.4)	7.7 (1.4)	7.6 (1.4)
Pulse (BPM (beats per minute)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [BPM (beats per minute)]	71.8 (10.0)	72.3 (10.0)	72.0 (10.0)
SBP (systolic blood pressure) (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	150.6 (11.0)	152.7 (12.1)	151.6 (11.6)
Weight (Kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms]	70.9 (10.6)	69.9 (13.2)	70.4 (12.0)

Outcome Measures

1. Primary Outcome

Title	Pulse Wave Velocity (PWV) Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug
Description	Analysis was performed in the modified intention to treat (mITT) population.
Time Frame	Baseline and 24 Weeks

Outcome Measure Data

Analysis Population Description

Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94). Missing data were imputed by the last observation carried forward (LOCF) technique.

Arm/Group Title	Losartan	Carvedilol
Arm/Group Description	Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.	Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.
Measure Participants	88	94
Mean (Standard Deviation) [meters/second]	0.28 (1.29)	-0.12 (1.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan, Carvedilol
	Comments	Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94).
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	non-inferiority margin= -1.5m/s
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95%; -0.83 to 0.01
	Parameter Dispersion	Type: Standard Deviation; Value: 1.43
	Estimation Comments	The lower limit of ≥-1.5m/s was judged to prove the non-inferiority of the test group to the control group.

2. Primary Outcome

Title	PWV Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug
Description	Analysis was performed in the per protocol (PP) population which additionally excludes certain protocol violations as described in the analysis plan.
Time Frame	Baseline and 24 Weeks

Outcome Measure Data

Analysis Population Description

Participants for analysis was per protocol (Number of patients: Losartan group was 54, Carvedilol group was 67). Missing data were imputed by the last observation carried forward (LOCF) technique. For the primary efficacy endpoints, Per protocol analysis approach was supplementary used.

Arm/Group Title	Losartan	Carvedilol
Arm/Group Description	Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration 4) did not commit major violation and 5) did not have protocol violation including erroneous prescription of the investigational drug, baseline PWV test date violation, PWV test date violation 24 weeks after the administration of the investigational drug, titration violation, use of prohibited concomitant drugs, visit window violation and inclusion/exclusion criteria violation.	Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration 4) did not commit major violation and 5) did not have protocol violation including erroneous prescription of the investigational drug, baseline PWV test date violation, PWV test date violation 24 weeks after the administration of the investigational drug, titration violation, use of prohibited concomitant drugs, visit window violation and inclusion/exclusion criteria violation.
Measure Participants	54	67
Mean (Standard Deviation) [meters/second]	0.16 (1.25)	-0.20 (1.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan, Carvedilol
	Comments	Participants for analysis was per protocol (Number of patients: Losartan group was 54, Carvedilol group was 67). For the primary efficacy endpoints, Per protocol analysis approach was supplementary used.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	non-inferiority margin=-1.5m/s
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.86 to 0.15
	Parameter Dispersion	Type: Standard Deviation; Value: 1.40
	Estimation Comments	The lower limit of ≥-1.5m/s was judged to prove the non-inferiority of the test group to the control group.

3. Secondary Outcome

Title	Systolic Blood Pressure (SBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94) Missing data were imputed by the last observation carried forward (LOCF) technique.

Arm/Group Title	Losartan	Carvedilol
Arm/Group Description	Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.	Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.
Measure Participants	88	94
Mean (Standard Deviation) [mm Hg]	-15.08 (14.59)	-14.81 (15.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan, Carvedilol
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9032
	Comments	Significance level=0.05
	Method	t-test, 2 sided
	Comments	The secondary efficacy analysis was performed in the modified intention to treat population using t-test.

4. Secondary Outcome

Title	Diastolic Blood Pressure (DBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94) Missing data were imputed by the last observation carried forward (LOCF) technique.

Arm/Group Title	Losartan	Carvedilol
Arm/Group Description	Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.	Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.
Measure Participants	88	94
Mean (Standard Deviation) [mm Hg]	-8.43 (9.29)	-7.81 (9.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan, Carvedilol
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6574
	Comments	Significance level=0.05
	Method	t-test, 2 sided
	Comments	The secondary efficacy analysis was performed in the modified intention to treat population using t-test

Adverse Events

Time Frame	Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.
Arm/Group Title	Losartan		Carvedilol
Arm/Group Description	Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Subjects who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who received the investigational drug at least more than once.		Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Subjects who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who received the investigational drug at least more than once.
All Cause Mortality
	Losartan		Carvedilol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Losartan		Carvedilol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/101 (5%)		6/100 (6%)
Cardiac disorders
Prinzmetal angina	1/101 (1%)	1	0/100 (0%)	0
Gastrointestinal disorders
Mouth haemorrhage	1/101 (1%)	1	0/100 (0%)	0
Infections and infestations
Chronic sinusitis	0/101 (0%)	0	1/100 (1%)	1
Injury, poisoning and procedural complications
Overdose	1/101 (1%)	1	5/100 (5%)	5
Ligament sprain	1/101 (1%)	1	0/100 (0%)	0
Nervous system disorders
Myelitis transverse	0/101 (0%)	0	1/100 (1%)	1
Vascular disorders
Haematoma	1/101 (1%)	1	0/100 (0%)	0
Other (Not Including Serious) Adverse Events
	Losartan		Carvedilol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/101 (34.7%)		51/100 (51%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/101 (1%)	1	0/100 (0%)	0
Cardiac disorders
Atrioventricular block first degree	1/101 (1%)	1	0/100 (0%)	0
Bradycardia	0/101 (0%)	0	1/100 (1%)	1
Palpitations	1/101 (1%)	1	0/100 (0%)	0
Ear and labyrinth disorders
Tinnitus	0/101 (0%)	0	1/100 (1%)	1
Eye disorders
Conjunctivitis	0/101 (0%)	0	1/100 (1%)	1
Eye pain	1/101 (1%)	1	0/100 (0%)	0
Gastrointestinal disorders
Dyspepsia	3/101 (3%)	3	3/100 (3%)	3
Nausea	0/101 (0%)	0	3/100 (3%)	3
Duodenal ulcer	0/101 (0%)	0	2/100 (2%)	2
Abdominal discomfort	1/101 (1%)	1	0/100 (0%)	0
Constipation	1/101 (1%)	1	0/100 (0%)	0
Diarrhoea	0/101 (0%)	0	1/100 (1%)	1
Gastric ulcer	0/101 (0%)	0	1/100 (1%)	1
Gastritis	1/101 (1%)	1	0/100 (0%)	0
Haemorrhoids	1/101 (1%)	1	0/100 (0%)	0
Melaena	0/101 (0%)	0	1/100 (1%)	1
Mouth ulceration	0/101 (0%)	0	1/100 (1%)	1
Periodontitis	0/101 (0%)	0	1/100 (1%)	1
Reflux gastritis	0/101 (0%)	0	1/100 (1%)	1
Reflux oesophagitis	0/101 (0%)	0	1/100 (1%)	1
Toothache	1/101 (1%)	1	0/100 (0%)	0
Vomiting	0/101 (0%)	0	1/100 (1%)	1
General disorders
Chest pain	2/101 (2%)	2	3/100 (3%)	3
Chest discomfort	2/101 (2%)	2	2/100 (2%)	2
Fatigue	0/101 (0%)	0	2/100 (2%)	2
Face oedema	0/101 (0%)	0	1/100 (1%)	1
Oedema peripheral	1/101 (1%)	1	0/100 (0%)	0
Infections and infestations
Nasopharyngitis	4/101 (4%)	4	7/100 (7%)	10
Acute sinusitis	0/101 (0%)	0	1/100 (1%)	1
Bronchiolitis	0/101 (0%)	0	1/100 (1%)	1
Herpes zoster	0/101 (0%)	0	1/100 (1%)	1
Pharyngitis	0/101 (0%)	0	1/100 (1%)	1
Pharyngotonsillitis	0/101 (0%)	0	1/100 (1%)	1
Upper respiratory tract infection	0/101 (0%)	0	1/100 (1%)	1
Injury, poisoning and procedural complications
Joint sprain	0/101 (0%)	0	1/100 (1%)	1
Metabolism and nutrition disorders
Hyperlipidaemia	1/101 (1%)	1	2/100 (2%)	2
Anorexia	0/101 (0%)	0	1/100 (1%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/101 (1%)	1	2/100 (2%)	2
Tendonitis	1/101 (1%)	1	1/100 (1%)	1
Musculoskeletal stiffness	0/101 (0%)	0	1/100 (1%)	1
Myofascial pain syndrome	0/101 (0%)	0	1/100 (1%)	1
Pain in extremity	1/101 (1%)	1	0/100 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign colonic neoplasm	0/101 (0%)	0	1/100 (1%)	1
Uterine leiomyoma	1/101 (1%)	1	0/100 (0%)	0
Nervous system disorders
Headache	8/101 (7.9%)	8	9/100 (9%)	12
Dizziness	5/101 (5%)	5	3/100 (3%)	3
Dizziness postural	0/101 (0%)	0	2/100 (2%)	2
Cerebral infarction	1/101 (1%)	1	0/100 (0%)	0
Hypoaesthesia	0/101 (0%)	0	1/100 (1%)	1
Migraine	1/101 (1%)	1	0/100 (0%)	0
Psychiatric disorders
Insomnia	1/101 (1%)	1	1/100 (1%)	1
Renal and urinary disorders
Pollakiuria	2/101 (2%)	2	1/100 (1%)	1
Haematuria	0/101 (0%)	0	2/100 (2%)	4
Dysuria	1/101 (1%)	1	0/100 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	0/101 (0%)	0	3/100 (3%)	3
Menopausal symptoms	1/101 (1%)	1	1/100 (1%)	1
Benign prostatic hyperplasia	1/101 (1%)	1	0/100 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/101 (1%)	1	1/100 (1%)	2
Cough	1/101 (1%)	1	0/100 (0%)	0
Nasal congestion	0/101 (0%)	0	1/100 (1%)	1
Productive cough	1/101 (1%)	1	0/100 (0%)	0
Rhinorrhoea	1/101 (1%)	1	0/100 (0%)	0
Upper respiratory tract inflammation	0/101 (0%)	0	1/100 (1%)	1
Skin and subcutaneous tissue disorders
Pruritus allergic	0/101 (0%)	0	1/100 (1%)	1
Rash maculo-papular	0/101 (0%)	0	1/100 (1%)	1
Urticaria	0/101 (0%)	0	1/100 (1%)	1
Surgical and medical procedures
Tooth extraction	0/101 (0%)	0	1/100 (1%)	1
Vascular disorders
Ischaemia	2/101 (2%)	2	0/100 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.