Efficacy and Safety Study of Fosamax Plus D in Postmenopausal Women With Osteoporosis (0217A-263)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00729651
• Collaborator: (none)
• Enrollment: 343
• Arms: 2
• Actual Duration (Months): 12.7

Study Details

Study Description

Brief Summary

To demonstrate the efficacy/safety of Fosamax Plus D

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis Postmenopausal	Drug: alendronate sodium (+) cholecalciferol; Drug: Comparator: Alendronate sodium (Fosamax); Dietary Supplement: Comparator: Calcium	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 343 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Open-label, Active-controlled Study to Evaluate the Efficacy and Safety of Fosamax Plus D in Postmenopausal Osteoporotic Women
• Actual Study Start Date: Mar 20, 2008
• Actual Primary Completion Date: Apr 10, 2009
• Actual Study Completion Date: Apr 10, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Alendronate sodium/Cholecalciferol	Drug: alendronate sodium (+) cholecalciferol; Alendronate sodium/Cholecalciferol; tablet, once weekly, for 16 weeks; Other Names: Fosamax Plus D ; Dietary Supplement: Comparator: Calcium; 500 mg oral tablet calcium once daily, for 16 weeks
Active Comparator: 2 Alendronate sodium	Drug: Comparator: Alendronate sodium (Fosamax); Alendronate sodium; tablet, once weekly, for 16 weeks; Dietary Supplement: Comparator: Calcium; 500 mg oral tablet calcium once daily, for 16 weeks

Outcome Measures

Primary Outcome Measures

1. Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Below the Deficiency Level (Less Than 15 ng/ml) at 16 Weeks of Treatment [16 weeks]

Secondary Outcome Measures

1. Serum PTH (Parathyroid Hormone) Percentage Changes From Baseline to 16 Weeks of Treatment [Baseline and 16 weeks]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient agrees to apply sunscreen and limit sunlight-exposure to 1 hour per day during the study

• Patient has been diagnosed with osteoporosis

• Patient has been postmenopausal for more than 6 months

• Patient has no contraindication to taking oral bisphosphonates

• Patient is eligible for dual energy x-ray absorptiometry in spine or hip

Exclusion Criteria:

• Patients with esophageal dysfunction

• Patients who can not sit or stand at least 30 minutes

• Patients who had a malignant disease or active systemic disease 5 years prior to participating in this trial

• Patients with diseases of bone or mineral metabolism besides osteoporosis or receiving therapies which affect bone metabolism or calcium metabolism

• Patients with history of major gastrointestinal disease (peptic ulcer, malabsorption, esophageal disease, gastritis, gastroduodenitis, etc.) within the last 6 months

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: NCT00729651
• Other Study ID Numbers: 0217A-263; MK0217A-263; 2008_015
• First Posted: Aug 7, 2008
• Last Update Posted: Feb 8, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Cholecalciferol; Vitamin D; Alendronate; Calcium

Study Results

Participant Flow

Recruitment Details	17 centers participated in this study (11 - Medical Center of the University, 7 - General Hospital). FPE(First patient enrolled) : March-2008, FPI(First patient in) : April-2008, LPO(Last patient out) : April-2009.

Arm/Group Title	Fosamax Plus D	Fosamax
Arm/Group Description	Once weekly Fosamax plus D tablet [Alendronate sodium 70 mg/Cholecalciferol 5600 IU] + once daily calcium formulation [500 mg/day]), 16 weeks	Once weekly Fosamax 70 mg tablet [Alendronate sodium 70 mg] + once daily calcium formulation [500 mg/day]), 16 weeks
Period Title: Overall Study
STARTED	173	170
COMPLETED	154	152
NOT COMPLETED	19	18

Baseline Characteristics

Arm/Group Title	Fosamax Plus D	Fosamax	Total
Arm/Group Description	Once weekly Fosamax plus D tablet [Alendronate sodium 70 mg/Cholecalciferol 5600 IU] + once daily calcium formulation [500 mg/day]), 16 weeks	Once weekly Fosamax 70 mg tablet [Alendronate sodium 70 mg] + once daily calcium formulation [500 mg/day]), 16 weeks	Total of all reporting groups
Overall Participants	173	170	343
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.59 (7.09)	65.31 (7.62)	64.94 (7.36)
Age, Customized (participants) [Number]
<=44 years of age	0 0%	0 0%	0 0%
45-49 years of age	1 0.6%	0 0%	1 0.3%
50-59 years of age	47 27.2%	43 25.3%	90 26.2%
60-69 years of age	85 49.1%	73 42.9%	158 46.1%
70-79 years of age	37 21.4%	51 30%	88 25.7%
>=80 years of age	3 1.7%	3 1.8%	6 1.7%
Sex: Female, Male (Count of Participants)
Female	173 100%	170 100%	343 100%
Male	0 0%	0 0%	0 0%
Patients with/without Vitamin D deficiency (participants) [Number]
With Vitamin D deficiency at baseline	57 32.9%	56 32.9%	113 32.9%
Without Vitamin D deficiency at baseline	116 67.1%	114 67.1%	230 67.1%
T-score classification by inclusion criteria: A fracture in spine Lumbar 1-4 and T-score ≤ -2.0] (Number) [Number]
A fracture in spine Lumbar 1-4 and T-score ≤ -2.0	9 5.2%	5 2.9%	14 4.1%
Not Applicable	164 94.8%	165 97.1%	329 95.9%
T-score classification by inclusion criteria: Femoral neck T-score ≤ -2.5 (Number) [Number]
Femoral neck T-score ≤ -2.5	43 24.9%	58 34.1%	101 29.4%
Not Applicable	130 75.1%	112 65.9%	242 70.6%
T-score classification by inclusion criteria: Femoral total T-score ≤ -2.5 (Number) [Number]
Femoral total T-score ≤ -2.5	20 11.6%	25 14.7%	45 13.1%
Not Applicable	153 88.4%	145 85.3%	298 86.9%
T-score classification by inclusion criteria: Spine (average of spine Lumbar 1-4 ) T-score ≤-2.5 (Number) [Number]
Spine (average of spine Lumbar 1-4 ) T-score ≤-2.5	144 83.2%	132 77.6%	276 80.5%
Not Applicable	29 16.8%	38 22.4%	67 19.5%
Two or more fractures in spine (Lumbar 1-4) (Number) [Number]
Two or more fractures in spine(Lumbar 1-4)	3 1.7%	4 2.4%	7 2%
Not Applicable	170 98.3%	166 97.6%	336 98%
A fracture in spine Lumbar 1, Lumbar 2, Lumbar 3, Lumbar 4 and T-score ≤-2.0 (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.44 (0.71)	-2.34 (0.3)	-2.40 (0.59)
Diastolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	72.5 (8.84)	73.82 (8.85)	73.15 (8.86)
Femoral neck T-score ≤ -2.5 (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.95 (0.48)	-2.94 (0.42)	-2.94 (0.45)
Femoral total T-score ≤ -2.5 (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-3.00 (0.52)	-3.00 (0.41)	-3.00 (0.46)
Height (Centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeters]	152.11 (5.88)	152.47 (5.59)	152.29 (5.73)
Serum PTH (Parathyroid hormone) (pg/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/ml]	25.27 (11.01)	23.47 (11.85)	24.38 (11.45)
Spine (average of spine Lumbar 1, Lumbar 2, Lumbar 3, Lumbar 4 ) T-score ≤ -2.5 (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.96 (0.40)	-3.06 (0.50)	-3.01 (0.45)
Systolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	122.83 (15.8)	124.08 (14.52)	123.45 (15.17)
Weight (Kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms]	53.84 (6.89)	54.8 (7.03)	54.32 (6.97)
serum 25 OHD (Serum 25-hydroxyvitamin D) (ng/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ml]	18.82 (6.46)	18.71 (6.25)	18.77 (6.35)

Outcome Measures

1. Primary Outcome

Title	Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Below the Deficiency Level (Less Than 15 ng/ml) at 16 Weeks of Treatment
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Participants for analysis was modified intention to treat (Number of patients : Fosamax Plus D Group was 136, Fosamax was 132). Missing data were imputed by the last observation carried forward (LOCF) technique.

Arm/Group Title	Fosamax Plus D	Fosamax
Arm/Group Description	Once weekly Fosamax plus D tablet [Alendronate sodium 70 mg/Cholecalciferol 5600 IU] + once daily calcium formulation [500 mg/day]), 16 weeks and patients who 1) received at least one dose of investigational product, 2) performed efficacy assessment including pre-treatment value and at least one post-treatment value, 3) did not have any major protocol violations including enrollment prior to contract and the violation of drug administration and entry criteria	Once weekly Fosamax 70 mg tablet [Alendronate sodium 70 mg] + once daily calcium formulation [500 mg/day], 16 weeks and patients who 1) received at least one dose of investigational product, 2) performed efficacy assessment including pre-treatment value and at least one post-treatment value, 3) did not have any major protocol violations including enrollment prior to contract and the violation of drug administration and entry criteria
Measure Participants	136	132
With Vitamin D Deficiency	2 1.2%	55 32.4%
Without Vitamin D Deficiency	134 77.5%	77 45.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosamax Plus D, Fosamax
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Primary efficacy endpoint was analyzed by a Cochran-Mantel-Haenszel test with baseline vitamin D level as covariate.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.02
	Confidence Interval	() 95%; 0.00 to 0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel estimator of the common odds ratio was calculated by using Cochran-Mantel-Haenszel test for subjects' proportions with vitamin D deficiency changes at 16 weeks (visit 4) from baseline (visit 1) between treatment groups.

2. Secondary Outcome

Title	Serum PTH (Parathyroid Hormone) Percentage Changes From Baseline to 16 Weeks of Treatment
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

Participants for analysis was modified intention to treat (Number of patients : Fosamax Plus D Group was 136, Fosamax was 132). Missing data were imputed by the last observation carried forward (LOCF) technique.

Arm/Group Title	Fosamax Plus D	Fosamax
Arm/Group Description	Once weekly Fosamax plus D tablet [Alendronate sodium 70 mg/Cholecalciferol 5600 IU] + once daily calcium formulation [500 mg/day]), 16 weeks and patients who 1) received at least one dose of investigational product, 2) performed efficacy assessment including pre-treatment value and at least one post-treatment value, 3) did not have any major protocol violations including enrollment prior to contract and the violation of drug administration and entry criteria	Once weekly Fosamax 70 mg tablet [Alendronate sodium 70 mg] + once daily calcium formulation [500 mg/day], 16 weeks and patients who 1) received at least one dose of investigational product, 2) performed efficacy assessment including pre-treatment value and at least one post-treatment value, 3) did not have any major protocol violations including enrollment prior to contract and the violation of drug administration and entry criteria
Measure Participants	136	132
Least Squares Mean (95% Confidence Interval) [Percentage Change Serum PTH]	8.17	29.98

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosamax Plus D, Fosamax
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0091
	Comments
	Method	ANCOVA
	Comments	Least squares mean is mean of serum PTH percentage changes adjusted serum PTH level at baseline.

3. Post-Hoc Outcome

Title	Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Less and Greater Than 20 ng/ml at 16 Weeks of Treatment
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Participants for analysis was modified intention to treat (Number of patients : Fosamax Plus D Group was 136, Fosamax was 132). Missing data were imputed by the last observation carried forward (LOCF) technique.

Arm/Group Title	Fosamax Plus D	Fosamax
Arm/Group Description	Once weekly Fosamax plus D tablet [Alendronate sodium 70 mg/Cholecalciferol 5600 IU] + once daily calcium formulation [500 mg/day]), 16 weeks and patients who 1) received at least one dose of investigational product, 2) performed efficacy assessment including pre-treatment value and at least one post-treatment value, 3) did not have any major protocol violations including enrollment prior to contract and the violation of drug administration and entry criteria	Once weekly Fosamax 70 mg tablet [Alendronate sodium 70 mg] + once daily calcium formulation [500 mg/day], 16 weeks and patients who 1) received at least one dose of investigational product, 2) performed efficacy assessment including pre-treatment value and at least one post-treatment value, 3) did not have any major protocol violations including enrollment prior to contract and the violation of drug administration and entry criteria
Measure Participants	136	132
With 25 OHD < 20ng/ml at 16 weeks of treatment	7 4%	93 54.7%
With 25 OHD >= 20ng/ml at 16 weeks of treatment	129 74.6%	39 22.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosamax Plus D, Fosamax
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	It was analyzed by a Cochran-Mantel-Haenszel test with baseline vitamin D level as covariate.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.02
	Confidence Interval	() 95%; 0.01 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel estimator of the common odds ratio was calculated by using Cochran-Mantel-Haenszel test for subjects' proportions with vitamin D deficiency changes at 16 weeks (visit 4) from baseline (visit 1) between treatment groups.

4. Post-Hoc Outcome

Title	Mean Serum 25 OHD(Serum 25-hydroxyvitamin D) at 16 Weeks of Treatment
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Participants for analysis was modified intention to treat (Number of patients : Fosamax Plus D Group was 136, Fosamax was 132). Missing data were imputed by the last observation carried forward (LOCF) technique.

Arm/Group Title	Fosamax Plus D	Fosamax
Arm/Group Description	Once weekly Fosamax plus D tablet [Alendronate sodium 70 mg/Cholecalciferol 5600 IU] + once daily calcium formulation [500 mg/day]), 16 weeks and patients who 1) received at least one dose of investigational product, 2) performed efficacy assessment including pre-treatment value and at least one post-treatment value, 3) did not have any major protocol violations including enrollment prior to contract and the violation of drug administration and entry criteria	Once weekly Fosamax 70 mg tablet [Alendronate sodium 70 mg] + once daily calcium formulation [500 mg/day], 16 weeks and patients who 1) received at least one dose of investigational product, 2) performed efficacy assessment including pre-treatment value and at least one post-treatment value, 3) did not have any major protocol violations including enrollment prior to contract and the violation of drug administration and entry criteria
Measure Participants	136	132
Mean (Standard Deviation) [ng/ml]	30.08 (5.87)	17.14 (6.04)

Adverse Events

Time Frame	Adverse events were followed up until 14 days after the last dose of investigational drug.
Adverse Event Reporting Description	1 Participant from Fosamax Plus D Group and 1 participant from Fosamax Group were not actually administered study drug after randomization and were exclude in AE reporting Group. 1 participant from Fosamax Plus D group was actually administered Fosamax and analyzed as Fosamax Group in AE reporting Group.
Arm/Group Title	Fosamax Plus D		Fosamax
Arm/Group Description	Once weekly Fosamax plus D tablet [Alendronate sodium 70 mg/Cholecalciferol 5600 IU] + once daily calcium formulation [500 mg/day]), 16 weeks and patients who received drugs at least once after randomization and was analyzed according to the actually administered study drugs		Once weekly Fosamax 70 mg tablet [Alendronate sodium 70 mg] + once daily calcium formulation [500 mg/day]), 16 weeks and patients who received drugs at least once after randomization and was analyzed according to the actually administered study drugs
All Cause Mortality
	Fosamax Plus D		Fosamax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fosamax Plus D		Fosamax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/171 (4.1%)		1/170 (0.6%)
General disorders
Pyrexia	1/171 (0.6%)	1	0/170 (0%)	0
Infections and infestations
Herpes zoster	1/171 (0.6%)	1	0/170 (0%)	0
Lung abscess	1/171 (0.6%)	1	0/170 (0%)	0
Otitis media	1/171 (0.6%)	1	0/170 (0%)	0
Pneumonia	1/171 (0.6%)	1	0/170 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	1/171 (0.6%)	1	0/170 (0%)	0
Osteochondrosis	0/171 (0%)	0	1/170 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	1/171 (0.6%)	1	0/170 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/171 (0.6%)	1	0/170 (0%)	0
Reproductive system and breast disorders
Cystocele	1/171 (0.6%)	1	0/170 (0%)	0
Uterine prolapse	1/171 (0.6%)	1	0/170 (0%)	0
Other (Not Including Serious) Adverse Events
	Fosamax Plus D		Fosamax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/171 (35.1%)		55/170 (32.4%)
Cardiac disorders
Palpitations	2/171 (1.2%)	2	0/170 (0%)	0
Ear and labyrinth disorders
Tinnitus	0/171 (0%)	0	1/170 (0.6%)	1
Eye disorders
Conjunctivitis	1/171 (0.6%)	1	0/170 (0%)	0
Vision blurred	1/171 (0.6%)	1	0/170 (0%)	0
Blepharitis	0/171 (0%)	0	1/170 (0.6%)	1
Dacryostenosis acquired	0/171 (0%)	0	1/170 (0.6%)	1
Gastrointestinal disorders
Dyspepsia	11/171 (6.4%)	11	18/170 (10.6%)	18
Nausea	3/171 (1.8%)	3	1/170 (0.6%)	1
Vomiting	3/171 (1.8%)	3	0/170 (0%)	0
Epigastric discomfort	2/171 (1.2%)	2	3/170 (1.8%)	3
Abdominal discomfort	1/171 (0.6%)	1	0/170 (0%)	0
Abdominal pain	1/171 (0.6%)	1	0/170 (0%)	0
Constipation	1/171 (0.6%)	1	0/170 (0%)	0
Diarrhoea	1/171 (0.6%)	1	1/170 (0.6%)	1
Gastritis atrophic	1/171 (0.6%)	1	0/170 (0%)	0
Abdominal pain upper	0/171 (0%)	0	1/170 (0.6%)	1
Gingivitis	0/171 (0%)	0	1/170 (0.6%)	1
Haemorrhoids	0/171 (0%)	0	1/170 (0.6%)	1
General disorders
Asthenia	2/171 (1.2%)	2	0/170 (0%)	0
Chest discomfort	2/171 (1.2%)	2	2/170 (1.2%)	2
Chills	2/171 (1.2%)	2	0/170 (0%)	0
Chest pain	1/171 (0.6%)	1	1/170 (0.6%)	1
Influenza like illness	0/171 (0%)	0	1/170 (0.6%)	1
Oedema peripheral	0/171 (0%)	0	1/170 (0.6%)	1
Thirst	0/171 (0%)	0	1/170 (0.6%)	1
Infections and infestations
Nasopharyngitis	8/171 (4.7%)	12	8/170 (4.7%)	9
Cystitis	2/171 (1.2%)	2	0/170 (0%)	0
Onychomycosis	1/171 (0.6%)	1	0/170 (0%)	0
Tinea pedis	1/171 (0.6%)	1	0/170 (0%)	0
Vaginal infection	1/171 (0.6%)	1	0/170 (0%)	0
Oral herpes	0/171 (0%)	0	1/170 (0.6%)	1
Upper respiratory tract infection	0/171 (0%)	0	3/170 (1.8%)	3
Injury, poisoning and procedural complications
Joint sprain	1/171 (0.6%)	1	0/170 (0%)	0
Radius fracture	1/171 (0.6%)	1	0/170 (0%)	0
Tibia fracture	1/171 (0.6%)	1	0/170 (0%)	0
Foot fracture	0/171 (0%)	0	1/170 (0.6%)	1
Investigations
Hepatic enzyme increased	0/171 (0%)	0	1/170 (0.6%)	1
Metabolism and nutrition disorders
Anorexia	0/171 (0%)	0	1/170 (0.6%)	1
Musculoskeletal and connective tissue disorders
Myalgia	7/171 (4.1%)	7	11/170 (6.5%)	11
Back pain	6/171 (3.5%)	6	1/170 (0.6%)	1
Arthralgia	4/171 (2.3%)	5	3/170 (1.8%)	3
Musculoskeletal pain	1/171 (0.6%)	1	3/170 (1.8%)	3
Pain in extremity	1/171 (0.6%)	1	1/170 (0.6%)	1
Joint stiffness	0/171 (0%)	0	1/170 (0.6%)	1
Musculoskeletal chest pain	0/171 (0%)	0	1/170 (0.6%)	1
Musculoskeletal disorder	0/171 (0%)	0	1/170 (0.6%)	1
Osteoarthritis	0/171 (0%)	0	1/170 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	1/171 (0.6%)	1	0/170 (0%)	0
Nervous system disorders
Headache	4/171 (2.3%)	4	2/170 (1.2%)	2
Dizziness	2/171 (1.2%)	2	2/170 (1.2%)	2
Cognitive disorder	1/171 (0.6%)	1	0/170 (0%)	0
Psychiatric disorders
Insomnia	1/171 (0.6%)	1	1/170 (0.6%)	1
Renal and urinary disorders
Nephrolithiasis	1/171 (0.6%)	1	0/170 (0%)	0
Nocturia	1/171 (0.6%)	1	0/170 (0%)	0
Polyuria	1/171 (0.6%)	1	0/170 (0%)	0
Haematuria	0/171 (0%)	0	1/170 (0.6%)	1
Urinary incontinence	0/171 (0%)	0	1/170 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/171 (0.6%)	1	0/170 (0%)	0
Dyspnoea	1/171 (0.6%)	1	0/170 (0%)	0
Productive cough	1/171 (0.6%)	1	0/170 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	3/171 (1.8%)	3	1/170 (0.6%)	1
Rash	1/171 (0.6%)	1	0/170 (0%)	0
Urticaria	0/171 (0%)	0	2/170 (1.2%)	2
Xeroderma	0/171 (0%)	0	1/170 (0.6%)	1
Vascular disorders
Hypertension	1/171 (0.6%)	1	0/170 (0%)	0
Flushing	0/171 (0%)	0	1/170 (0.6%)	1

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.