A Study to Test the Effect of MK0217A on Vitamin D Inadequacy in Postmenopausal Women With Osteoporosis (0217A-262)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00692913
• Collaborator: (none)
• Enrollment: 515
• Arms: 2
• Duration (Months): 25

Study Details

Study Description

Brief Summary

A study designed to see if the study drug will increase blood levels of vitamin D, bone mineral density (BMD), improve biochemical markers of bone turnover, and reduce the number of falls as compared to women receiving standard care for osteoporosis.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: FOSAVANCE 5600 (Alendronate Sodium (+) cholecalciferol); Dietary Supplement: Calcium Supplement 500 mg; Other: Referred-Care Model	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 515 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III (Phase V Program), Open-Label, Randomized, Referred-Care-Controlled, Clinical Trial to Evaluate the Efficacy and Safety of MK -0217A/Alendronate Sodium-70 mg/Vitamin D3 5600 I.U. Combination Tablet on Vitamin D Inadequacy in the Treatment of Osteoporosis in Postmenopausal Women
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FOSAVANCE 5600 alendronate sodium (+) cholecalciferol	Drug: FOSAVANCE 5600 (Alendronate Sodium (+) cholecalciferol); FOSAVANCE 5600 international units (IU)(Alendronate Sodium 70 mg/Vitamin D 5600 IU) combination tablet once weekly for 6 months (Week 26) during the base period and an additional 6-month extension period (Week 52).; Dietary Supplement: Calcium Supplement 500 mg; Calcium supplied locally by the investigator (containing 500 mg calcium supplement) daily for 52 weeks (unless the patient's dietary intake of calcium exceeds 1000 mg per day).
Other: Referred-Care Model Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.	Other: Referred-Care Model; Usual treatment for osteoporosis chosen and prescribed by patients' own physicians for 6 months (Week 26) during the base period and an additional 6-month extension period (Week 52).

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 26 [Week 26]

   Percentage of participants with serum levels of 25-hydroxyvitamin D below 20 nanograms/milliliter (ng/mL) after 26 weeks of treatment with FOSAVANCE 5600 once weekly versus Referred-Care in postmenopausal women with osteoporosis and at increased risk of falls.

Secondary Outcome Measures

1. Percent Change From Baseline at Week 26 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio [Baseline and Week 26]

   N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio (NTx) is a urine biochemical marker of bone resorption and measured in nanomoles (nmol) Bone Collagen Equivalents (BCE)/millimoles (mmol) creatinine. The percent change was calculated as: [100 * ((Week 26/Baseline)-1)]. The greater the percent decrease from baseline, the greater the response to therapy.

2. Percent Change From Baseline at Week 26 in Bone-Specific Alkaline Phosphatase [Baseline and Week 26]

   Bone-Specific Alkaline Phosphatase (BSAP) is a serum biochemical marker of bone formation and measured in micrograms/Liter (mcg/L). The percent change was calculated as: [100 * ((Week 26/Baseline)-1)]. The greater the percent decrease from baseline, the greater the response to therapy.

3. Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 52 [Week 52]

   Percentage of participants with serum levels of 25-hydroxyvitamin D below 20 ng/mL after 52 weeks of treatment (6 month extension study) with FOSAVANCE 5600 once weekly versus Referred-Care in postmenopausal women with osteoporosis and at increased risk of falls.

4. Percent Change From Baseline in Lumbar Spine and Total Hip Bone Mineral Density [Baseline and Week 52]

   Bone Mineral Density (BMD) as measured by Dual Energy X-Ray Absorptiometry (DEXA) and measured in g/cm^2 was obtained at baseline (visit 1) and Week 52 (visit 13) or at early study discontinuation visit. The percent change was calculated as: [100 * ((Week 52/Baseline)-1)]. The greater the percent change from baseline, the greater the response to therapy.

5. Falls Per Participant [Up to Week 52]

   Number of falls per participant was measured. The fall event rate during the study period was defined as the number of adjudicated falls during the study period divided by the total patient-years in the study. Each participant was to be in the study for approximately one year. In order to guide and standardize all procedures during the fall adjudication process, a Standard Operating Procedure for Fall Adjudication was created by the SPONSOR and served as a guideline to standardize operational procedures for fall adjudication.

6. Percent Change From Baseline at Week 52 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio [Baseline and Week 52]

   NTx is a urine biochemical marker of bone resorption and measured in nanomoles (nmol) Bone Collagen Equivalents (BCE)/millimoles (mmol) creatinine. The percent change was calculated as: [100 * ((Week 52/Baseline)-1)]. The greater the percent decrease from baseline, the greater the response to therapy.

7. Percent Change From Baseline at Week 52 in Bone-Specific Alkaline Phosphatase [Baseline and Week 52]

   BSAP is a serum biochemical marker of bone formation and measured in micrograms/Liter (mcg/L). The percent change was calculated as: [100 * ((Week 52/Baseline)-1)]. The greater the percent decrease from baseline, the greater the response to therapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female

• 65 years or older

• Diagnosed with osteoporosis (Bone Mineral Density (BMD) T-score <= -2.5 at spine or hip) or prior fragility fracture BMD T-score <=-1.5 in at least one of the anatomic sites including lumbar spine, total hip, and femoral neck sites

• Postmenopausal

• Low levels of vitamin D as measured 25-hydroxyvitamin D

• Has fallen at least once within the past 12 months

Exclusion Criteria:

• Unable to stand or sit upright for at least 30 minutes

• Has a bone disorder other than osteoporosis

• Contraindication to the use of FOSAVANCE

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

• Ralston SH, Binkley N, Boonen S, Kiel DP, Reginster JY, Roux C, Chen L, Rosenberg E, Santora A; FOCUS-D (FOSAVANCE vs. Standard Care-Use and Study of Vitamin D) Trial. Randomized trial of alendronate plus vitamin D3 versus standard care in osteoporotic postmenopausal women with vitamin D insufficiency. Calcif Tissue Int. 2011 Jun;88(6):485-94. doi: 10.1007/s00223-011-9482-4. Epub 2011 Apr 11.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00692913
• Other Study ID Numbers: 0217A-262; 2007_653
• First Posted: Jun 6, 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; Cholecalciferol; Vitamin D; Alendronate; Calcium

Study Results

Participant Flow

Arm/Group Title	FOSAVANCE 5600	Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
Period Title: Overall Study
STARTED	257	258
COMPLETED	228	228
NOT COMPLETED	29	30

Baseline Characteristics

Arm/Group Title	FOSAVANCE 5600	Referred-Care	Total
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.	Total of all reporting groups
Overall Participants	257	258	515
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.9 (5.3)	72.9 (5.9)	72.9 (5.6)
Sex: Female, Male (Count of Participants)
Female	257 100%	258 100%	515 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 26
Description	Percentage of participants with serum levels of 25-hydroxyvitamin D below 20 nanograms/milliliter (ng/mL) after 26 weeks of treatment with FOSAVANCE 5600 once weekly versus Referred-Care in postmenopausal women with osteoporosis and at increased risk of falls.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Full Analysis Set Population (FAS) included participants who took at least one dose of study therapy during the entire treatment period of FOSAVANCE 5600 or who were assigned to receive regular care and had data reported at least once post-randomization during the entire study period, and had efficacy measurements during the entire study period.

Arm/Group Title	FOSAVANCE 5600	Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
Measure Participants	221	216
Number [Percentage of Participants]	8.6 3.3%	31.0 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOSAVANCE 5600, Referred-Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments	The logistic regression model was adjusted by baseline 25-hydroxyvitamin D (25(OH)D) level stratum, age, and region.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.20
	Confidence Interval	() 95%; 0.12 to 0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline at Week 26 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio
Description	N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio (NTx) is a urine biochemical marker of bone resorption and measured in nanomoles (nmol) Bone Collagen Equivalents (BCE)/millimoles (mmol) creatinine. The percent change was calculated as: [100 * ((Week 26/Baseline)-1)]. The greater the percent decrease from baseline, the greater the response to therapy.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

Per-Protocol Population: excluded participants due to important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.

Arm/Group Title	FOSAVANCE 5600	Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
Measure Participants	216	226
Least Squares Mean (95% Confidence Interval) [Percent Change]	-57.06	-47.36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOSAVANCE 5600, Referred-Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Longitudinal Data Analysis Model
	Comments	The model was adjusted by baseline 25-hydroxyvitamin D level stratum, age, and region.
Method of Estimation	Estimation Parameter	Difference in Least-squares means
	Estimated Value	-9.70
	Confidence Interval	() 95%; -14.49 to -4.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline at Week 26 in Bone-Specific Alkaline Phosphatase
Description	Bone-Specific Alkaline Phosphatase (BSAP) is a serum biochemical marker of bone formation and measured in micrograms/Liter (mcg/L). The percent change was calculated as: [100 * ((Week 26/Baseline)-1)]. The greater the percent decrease from baseline, the greater the response to therapy.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

Per-Protocol Population: excluded participants due to important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.

Arm/Group Title	FOSAVANCE 5600	Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
Measure Participants	223	237
Least Squares Mean (95% Confidence Interval) [Percent Change]	-46.67	-39.60

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOSAVANCE 5600, Referred-Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Longitudinal Data Analysis Model
	Comments	The model was adjusted by baseline 25-hydroxyvitamin D level stratum, age, and region.
Method of Estimation	Estimation Parameter	Difference in Least-squares mean
	Estimated Value	-7.07
	Confidence Interval	() 95%; -10.95 to -3.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 52
Description	Percentage of participants with serum levels of 25-hydroxyvitamin D below 20 ng/mL after 52 weeks of treatment (6 month extension study) with FOSAVANCE 5600 once weekly versus Referred-Care in postmenopausal women with osteoporosis and at increased risk of falls.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The FAS population included participants who took at least one dose of study therapy during the entire treatment period of FOSAVANCE 5600 or who were assigned to receive regular care and had data reported at least once post-randomization during the entire study period, and had efficacy measurements during the entire study period.

Arm/Group Title	FOSAVANCE 5600	Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
Measure Participants	212	203
Number [Percentage of Participants]	11.3 4.4%	36.9 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOSAVANCE 5600, Referred-Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments	The logistic regression model was adjusted by baseline 25-hydroxyvitamin D level stratum, age, and region.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.21
	Confidence Interval	() 95%; 0.13 to 0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine and Total Hip Bone Mineral Density
Description	Bone Mineral Density (BMD) as measured by Dual Energy X-Ray Absorptiometry (DEXA) and measured in g/cm^2 was obtained at baseline (visit 1) and Week 52 (visit 13) or at early study discontinuation visit. The percent change was calculated as: [100 * ((Week 52/Baseline)-1)]. The greater the percent change from baseline, the greater the response to therapy.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The FAS population included participants who took at least one dose of study therapy during the entire treatment period of FOSAVANCE 5600 or who were assigned to receive regular care and had data reported at least once post-randomization during the entire study period, and had efficacy measurements during the entire study period.

Arm/Group Title	FOSAVANCE 5600	Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
Measure Participants	227	219
Lumbar Spine (n= 226/ n=219)	4.92	3.91
Total Hip (n=227/ n=218)	2.22	1.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOSAVANCE 5600, Referred-Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	Traditional Longitudinal data analysis
	Comments	The model was adjusted by baseline 25-hydroxyvitamin D level stratum, age, and region.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	1.01
	Confidence Interval	() 95%; 0.01 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	FOSAVANCE minus Referred-Care. Analysis was for Lumbar Spine.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FOSAVANCE 5600, Referred-Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	Traditional Longitudinal data analysis
	Comments	The model was adjusted by baseline 25-hydroxyvitamin D level stratum, age, and region.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.82
	Confidence Interval	() 95%; 0.06 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	FOSAVANCE minus Referred-Care. Analysis was for Total Hip.

6. Secondary Outcome

Title	Falls Per Participant
Description	Number of falls per participant was measured. The fall event rate during the study period was defined as the number of adjudicated falls during the study period divided by the total patient-years in the study. Each participant was to be in the study for approximately one year. In order to guide and standardize all procedures during the fall adjudication process, a Standard Operating Procedure for Fall Adjudication was created by the SPONSOR and served as a guideline to standardize operational procedures for fall adjudication.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all randomized participants within the treatment group to which they were randomized regardless of whether or not a participant may have dropped out in the base or continued into the extension study.

Arm/Group Title	FOSAVANCE 5600	Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
Measure Participants	257	258
Mean (Standard Deviation) [Number of Falls]	0.51 (1.53)	0.45 (0.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOSAVANCE 5600, Referred-Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.675
	Comments
	Method	Zero-Inflated Poisson Regression
	Comments	Adjusted by the terms for treatment, baseline 25(OH) D level stratum, age, and region and offset variable of log (total patient-years in the study).
Method of Estimation	Estimation Parameter	Difference of falls (falls/patient-year)
	Estimated Value	0.03
	Confidence Interval	() 95%; -0.12 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

7. Secondary Outcome

Title	Percent Change From Baseline at Week 52 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio
Description	NTx is a urine biochemical marker of bone resorption and measured in nanomoles (nmol) Bone Collagen Equivalents (BCE)/millimoles (mmol) creatinine. The percent change was calculated as: [100 * ((Week 52/Baseline)-1)]. The greater the percent decrease from baseline, the greater the response to therapy.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Per-Protocol Population: excluded patients due to important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.

Arm/Group Title	FOSAVANCE 5600	Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
Measure Participants	216	227
Least Squares Mean (95% Confidence Interval) [Percent Change]	-58.42	-50.07

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOSAVANCE 5600, Referred-Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Longitudinal Data Analysis Model
	Comments	The model was adjusted by baseline 25-hydroxyvitamin D level stratum, age, and region.
Method of Estimation	Estimation Parameter	Difference in Least Squares Means
	Estimated Value	-8.35
	Confidence Interval	() 95%; -13.19 to -3.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percent Change From Baseline at Week 52 in Bone-Specific Alkaline Phosphatase
Description	BSAP is a serum biochemical marker of bone formation and measured in micrograms/Liter (mcg/L). The percent change was calculated as: [100 * ((Week 52/Baseline)-1)]. The greater the percent decrease from baseline, the greater the response to therapy.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Per-Protocol Population: excluded patients due to important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.

Arm/Group Title	FOSAVANCE 5600	Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.	Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
Measure Participants	223	237
Least Squares Mean (95% Confidence Interval) [Percent Change]	-51.21	-43.13

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOSAVANCE 5600, Referred-Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Longitudinal Data Analysis Model
	Comments	The model was adjusted by baseline 25-hydroxyvitamin D level stratum, age, and region.
Method of Estimation	Estimation Parameter	Difference in Least Squares Mean
	Estimated Value	-8.07
	Confidence Interval	() 95%; -11.94 to -4.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	FOSAVANCE 5600 group: participants who took at least 1 dose were included (254 out of 257 patients). All patients randomized in the referred-care group were included regardless of whether they took 1 dose of therapy as prescribed by their physicians.
Arm/Group Title	FOSAVANCE 5600		Referred-Care
Arm/Group Description	Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement.		Usual treatment for osteoporosis chosen and prescribed by patients' own physicians.
All Cause Mortality
	FOSAVANCE 5600		Referred-Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FOSAVANCE 5600		Referred-Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/254 (9.8%)		29/258 (11.2%)
Cardiac disorders
Angina Unstable	0/254 (0%)	0	1/258 (0.4%)	1
Atrial Fibrillation	3/254 (1.2%)	3	1/258 (0.4%)	2
Cardiac Failure	1/254 (0.4%)	1	0/258 (0%)	0
Coronary Artery Disease	2/254 (0.8%)	2	0/258 (0%)	0
Electromechanical Dissociation	1/254 (0.4%)	1	0/258 (0%)	0
Myocardial Infarction	0/254 (0%)	0	1/258 (0.4%)	1
Sick Sinus Syndrome	1/254 (0.4%)	1	0/258 (0%)	0
Eye disorders
Eye Haemorrhage	0/254 (0%)	0	1/258 (0.4%)	1
Gastrointestinal disorders
Abdominal Pain Upper	0/254 (0%)	0	1/258 (0.4%)	1
Diarrhoea	1/254 (0.4%)	1	0/258 (0%)	0
Faecaloma	0/254 (0%)	0	1/258 (0.4%)	1
Gastric Ulcer	1/254 (0.4%)	1	0/258 (0%)	0
Gastroesophageal Reflux Disease	1/254 (0.4%)	1	0/258 (0%)	0
Intestinal Obstruction	0/254 (0%)	0	1/258 (0.4%)	1
Retroperitoneal Haemorrhage	1/254 (0.4%)	1	0/258 (0%)	0
Vomiting	0/254 (0%)	0	1/258 (0.4%)	1
General disorders
Chest Pain	1/254 (0.4%)	1	0/258 (0%)	0
Local Swelling	0/254 (0%)	0	1/258 (0.4%)	1
Non-Cardiac Chest Pain	1/254 (0.4%)	1	1/258 (0.4%)	1
Pyrexia	1/254 (0.4%)	1	0/258 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/254 (0%)	0	1/258 (0.4%)	1
Infections and infestations
Bacterial Diarrhoea	0/254 (0%)	0	1/258 (0.4%)	1
Bronchitis	1/254 (0.4%)	1	0/258 (0%)	0
Diverticulitis	0/254 (0%)	0	1/258 (0.4%)	1
Enterovirus Infection	0/254 (0%)	0	1/258 (0.4%)	1
Gastroenteritis Viral	1/254 (0.4%)	1	0/258 (0%)	0
Malaria	1/254 (0.4%)	1	0/258 (0%)	0
Peritonsillar Abscess	1/254 (0.4%)	1	0/258 (0%)	0
Pneumonia	0/254 (0%)	0	1/258 (0.4%)	1
Sepsis	1/254 (0.4%)	1	0/258 (0%)	0
Subacute Endocarditis	1/254 (0.4%)	1	0/258 (0%)	0
Urinary Tract Infection	1/254 (0.4%)	1	0/258 (0%)	0
Injury, poisoning and procedural complications
Ankle Fracture	1/254 (0.4%)	1	0/258 (0%)	0
Contusion	0/254 (0%)	0	2/258 (0.8%)	2
Hip Fracture	0/254 (0%)	0	2/258 (0.8%)	2
Meniscus Lesion	0/254 (0%)	0	1/258 (0.4%)	1
Pubis Fracture	0/254 (0%)	0	1/258 (0.4%)	1
Metabolism and nutrition disorders
Dehydration	0/254 (0%)	0	1/258 (0.4%)	1
Musculoskeletal and connective tissue disorders
Back Pain	1/254 (0.4%)	1	1/258 (0.4%)	1
Intervertebral Disc Protrusion	0/254 (0%)	0	1/258 (0.4%)	1
Lumbar Spinal Stenosis	0/254 (0%)	0	1/258 (0.4%)	1
Osteoarthritis	0/254 (0%)	0	1/258 (0.4%)	1
Spinal Column Stenosis	1/254 (0.4%)	1	1/258 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	1/254 (0.4%)	1	2/258 (0.8%)	3
Colon Cancer	0/254 (0%)	0	1/258 (0.4%)	1
Oesophageal Squamous Cell Carcinoma	1/254 (0.4%)	1	0/258 (0%)	0
Ovarian Epithelial Cancer	1/254 (0.4%)	1	0/258 (0%)	0
Pancreatic Carcinoma	1/254 (0.4%)	1	0/258 (0%)	0
Uterine Cancer	1/254 (0.4%)	1	0/258 (0%)	0
Nervous system disorders
Carotid Artery Stenosis	0/254 (0%)	0	1/258 (0.4%)	1
Cerebral Ischaemia	1/254 (0.4%)	1	0/258 (0%)	0
Cerebrovascular Accident	1/254 (0.4%)	1	0/258 (0%)	0
Facial Palsy	0/254 (0%)	0	1/258 (0.4%)	1
Radiculopathy	1/254 (0.4%)	1	0/258 (0%)	0
Transient Ischaemic Attack	0/254 (0%)	0	1/258 (0.4%)	1
Unresponsive to Stimuli	1/254 (0.4%)	1	0/258 (0%)	0
Vascular Dementia	0/254 (0%)	0	1/258 (0.4%)	1
Renal and urinary disorders
Haematuria	0/254 (0%)	0	1/258 (0.4%)	1
Nephrolithiasis	0/254 (0%)	0	1/258 (0.4%)	1
Renal Artery Stenosis	0/254 (0%)	0	1/258 (0.4%)	1
Renal Failure Acute	1/254 (0.4%)	1	0/258 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/254 (0.4%)	1	0/258 (0%)	0
Dyspnoea	1/254 (0.4%)	2	0/258 (0%)	0
Pulmonary Congestion	1/254 (0.4%)	1	0/258 (0%)	0
Respiratory Failure	1/254 (0.4%)	1	0/258 (0%)	0
Vascular disorders
Orthostatic Hypotension	0/254 (0%)	0	1/258 (0.4%)	1
Peripheral Arterial Occlusive disease	0/254 (0%)	0	1/258 (0.4%)	1
Thrombophlebitis Superficial	1/254 (0.4%)	1	0/258 (0%)	0
Other (Not Including Serious) Adverse Events
	FOSAVANCE 5600		Referred-Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/254 (24%)		70/258 (27.1%)
Gastrointestinal disorders
Diarrhoea	8/254 (3.1%)	9	13/258 (5%)	14
Infections and infestations
Urinary Tract Infection	12/254 (4.7%)	12	14/258 (5.4%)	18
Injury, poisoning and procedural complications
Contusion	13/254 (5.1%)	21	14/258 (5.4%)	19
Musculoskeletal and connective tissue disorders
Arthralgia	20/254 (7.9%)	24	21/258 (8.1%)	23
Back Pain	12/254 (4.7%)	14	21/258 (8.1%)	22
Nervous system disorders
Dizziness	9/254 (3.5%)	10	13/258 (5%)	17

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts,or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.