A Study of Adherence to Once Monthly Ibandronate (Bonviva) in Women With Post-Menopausal Osteoporosis, Supported by a Patient Relationship Program (PRP)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00545363
• Collaborator: (none)
• Enrollment: 716
• Locations: 52
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 13.8
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This 2 arm study will assess the impact of bone marker feedback (BMF), using serum carboxy-terminal collagen crosslinks (CTX) and communication of results at 3 months, on adherence to once monthly ibandronate (150 milligrams [mg] per oral [po]) in women with post-menopausal osteoporosis supported by patient-relationship program (PRP). Participants will be randomized either to receive BMF or no BMF; both groups will be supported by PRP. The anticipated time on study treatment is 3-12 months.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: Ibandronate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 716 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Open-Label Study to Investigate the Impact of Bone Marker Feedback at 3 Months on Adherence to Monthly Oral Bonviva in Women With Post-Menopausal Osteoporosis Supported by a Patient Relationship Program
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bone Marker Feedback (BMF) Participants Postmenopausal women will receive ibandronate 150 milligrams (mg) once monthly (QM) orally for 6 months. Participants, in this arm, will receive BMF at Month 3. BMF will be given in terms of providing serum carboxy-terminal collagen crosslinks (CTX) level at Month 3. A "BMF-form" will be provided to the physicians to allow offering the bone marker result in an easy way. Participants will be informed if their results are within or outside of the desired range. In addition, participants will also supported by PRP, to be carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.	Drug: Ibandronate; Participants will receive ibandronate 150 mg QM orally for 6 months.; Other Names: Bonviva Boniva
Active Comparator: No BMF Participants Postmenopausal women will receive ibandronate 150 milligrams (mg) once monthly (QM) orally for 6 months. Participants will be supported by PRP, to be carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.	Drug: Ibandronate; Participants will receive ibandronate 150 mg QM orally for 6 months.; Other Names: Bonviva Boniva

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adherence to Treatment [Up to 6 months]

   Participants were considered adherent to treatment if they took at least 83 percent (%) of their assigned medications (5 of the 6 monthly ibandronate tablets) within the -1 to +21 days of their osteoporosis treatment date each month. Participant adherence was assessed by maintaining records of 'drug dispensed' and 'drug returned' on case report form (CRF) and participant's self-report on Visit 2 (Month 3) and final study visit (Month 6). A drug dispensing log was maintained by the investigator. Participants were instructed at the baseline visit and Visit 2 to save and return unused or partially used medication packages on Visit 2 and final study visit, respectively.

Secondary Outcome Measures

1. Percentage of Participants With Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) Composite Satisfaction High Scores [At Month 6]

   The OPSAT-Q is a validated questionnaire designed to capture satisfaction with bisphosphonate treatment. It comprises four domains: convenience (questions 1 - 6), quality of life (questions 7 and 8), overall satisfaction (questions 9 and 10), and side effects (questions 11 - 16). Satisfaction with treatment was assessed using the OPSAT-Q composite satisfaction score, which was the average of the scores from the four domains of the OPSAT-Q converted to a 0 - 100-point scale. Higher scores indicated greater treatment satisfaction. A score of 80 or more was considered as high score.

2. Percentage of Participants With Osteoporosis Patient Perception Survey (OPPS) and Osteoporosis Medical Care Satisfaction Questionnaire (OMSQ) Composite Satisfaction High Score [At Month 6]

   OPPS: A standardized 6-item satisfaction questionnaire for osteoporosis medical care and treatment received during the study. Individual item score was transformed and converted to a 0 to 100 scale where higher score indicated greater satisfaction. The composite score was the average of individual item scores (transformed) and ranged from 0 to 100, where higher scores indicated greater satisfaction. OMSQ: A standardized 18-item satisfaction questionnaire for osteoporosis medical care, treatment received and blood test and their results during the study. Individual item score was transformed and converted to a 0 to 100 scale where higher score indicated greater satisfaction. The composite score was the average of individual item scores (transformed) and ranged from 0 to 100, where higher scores indicated greater satisfaction.

3. Percent Change From Baseline in CTX Based on Adherence to Ibandronate [Baseline, Month 6]

   Serum CTX, a biochemical marker of bone resorption, was assessed for all participants at baseline and at final visit (Month 6). The sampling was done at the same time of the day each time to overcome the effect of circadian fluctuations. Participants were considered adherent to treatment if they took at least 83% of their assigned medications (5 of the 6 monthly ibandronate tablets) within the -1 to +21 days of their osteoporosis treatment date each month. Participant adherence was assessed by maintaining records of 'drug dispensed' and 'drug returned' on CRF and participant's self-report on Visit 2 (Month 3) and final study visit (Month 6). A drug dispensing log was maintained by the investigator. Participants were instructed at the baseline visit and Visit 2 to save and return unused or partially used medication packages on Visit 2 and final study visit, respectively.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ambulatory, post-menopausal women with osteoporosis;

• eligible for bisphosphonate treatment;

• naïve to bisphosphonate therapy, or lapsed users (last bisphosphonate intake greater than or equal to [>=] 6 months ago).

Exclusion Criteria:

• inability to stand or sit upright for at least 60 minutes;

• inability to swallow a tablet whole;

• hypersensitivity to bisphosphonates;

• treatment with drugs, or presence of active disease, known to influence bone metabolism;

• history of upper gastrointestinal disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Budapest		Hungary	1027
2		Budapest		Hungary	1032
3		Budapest		Hungary	1113
4		Békéscsaba		Hungary	5600
5		Debrecen		Hungary	4043
6		Miskolc		Hungary	3529
7		Pecs		Hungary	7624
8		Szeged		Hungary	6720
9		Szekesfehervar		Hungary	8000
10		Szombathely		Hungary	9700
11		Liepaja		Latvia	3400
12		Riga		Latvia	1004
13		Riga		Latvia	1038
14		Riga		Latvia	LV-1012
15		Gliwice		Poland	44-100
16		Krakow		Poland	30-510
17		Lodz		Poland	90-549
18		Poznan		Poland	60-355
19		Warszawa		Poland	00-719
20		Warszawa		Poland	00-909
21		Warszawa		Poland	02-507
22		Warszawa		Poland	02-637
23		Wroclaw		Poland	50-367
24		Bucharest		Romania	011172
25		Bucharest		Romania	011364
26		Bucharest		Romania	011461
27		Bucharest		Romania	011863
28		Cluj-napoca		Romania	400006
29		Constanta		Romania	900709
30		Craiova		Romania	300941
31		Timisoara		Romania	300736
32		Ekaterinburg		Russian Federation	620102
33		Irkutsk		Russian Federation	664047
34		Moscow		Russian Federation	101990
35		Moscow		Russian Federation	111123
36		Moscow		Russian Federation	115552
37		Moscow		Russian Federation	117036
38		Moscow		Russian Federation	117997
39		Moscow		Russian Federation	125315
40		Moscow		Russian Federation	127299
41		Moscow		Russian Federation	127473
42		Moscow		Russian Federation	129110
43		St Petersburg		Russian Federation	190068
44		St Petersburg		Russian Federation	199034
45		Voronezh		Russian Federation	394066
46		Yaroslavl		Russian Federation	150003
47		Banska Bystrica		Slovakia	975 17
48		Bratislava		Slovakia	826 06
49		Lubochna		Slovakia	034 91
50		Piestany		Slovakia	921 12
51		Presov		Slovakia	080 01
52		Ljubljana		Slovenia	1525

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00545363
• Other Study ID Numbers: ML19982; 2005-005529-74
• First Posted: Oct 17, 2007
• Last Update Posted: Oct 24, 2016
• Last Verified: Aug 1, 2016

• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Ibandronic Acid

Study Results

Participant Flow

Arm/Group Title	Bone Marker Feedback (BMF) Participants	No BMF Participants
Arm/Group Description	Postmenopausal women received ibandronate 150 milligrams (mg) once monthly (QM) orally for 6 months. Participants, in this arm, received bone marker feedback (BMF) at Month 3. BMF was given in terms of providing serum carboxy-terminal collagen crosslinks (CTX) level at Month 3. A "BMF-form" was provided to the physicians to allow offering the bone marker result in an easy way. Participants were informed that their results were within or outside of the desired range. In addition, participants were also supported by patient relationship program (PRP), carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants were supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.
Period Title: Overall Study
STARTED	358	358
Treated	354	357
COMPLETED	339	343
NOT COMPLETED	19	15

Baseline Characteristics

Arm/Group Title	BMF Participants	No BMF Participants	Total
Arm/Group Description	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants, in this arm, received BMF at Month 3. BMF was given in terms of providing serum CTX level at Month 3. A "BMF-form" was provided to the physicians to allow offering the bone marker result in an easy way. Participants were informed that their results were within or outside of the desired range. In addition, participants were also supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants were supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.	Total of all reporting groups
Overall Participants	354	357	711
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.7 (7.12)	65.6 (6.64)	66.2 (6.90)
Sex: Female, Male (Count of Participants)
Female	354 100%	357 100%	711 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adherence to Treatment
Description	Participants were considered adherent to treatment if they took at least 83 percent (%) of their assigned medications (5 of the 6 monthly ibandronate tablets) within the -1 to +21 days of their osteoporosis treatment date each month. Participant adherence was assessed by maintaining records of 'drug dispensed' and 'drug returned' on case report form (CRF) and participant's self-report on Visit 2 (Month 3) and final study visit (Month 6). A drug dispensing log was maintained by the investigator. Participants were instructed at the baseline visit and Visit 2 to save and return unused or partially used medication packages on Visit 2 and final study visit, respectively.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population included all randomized participants. Number of participants analyzed=number of participants evaluable for this outcome.

Arm/Group Title	BMF Participants	No BMF Participants
Arm/Group Description	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants, in this arm, received BMF at Month 3. BMF was given in terms of providing serum CTX level at Month 3. A "BMF-form" was provided to the physicians to allow offering the bone marker result in an easy way. Participants were informed that their results were within or outside of the desired range. In addition, participants were also supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants were supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.
Measure Participants	271	284
Number [percentage of participants]	98.5 27.8%	98.6 27.6%

2. Secondary Outcome

Title	Percentage of Participants With Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) Composite Satisfaction High Scores
Description	The OPSAT-Q is a validated questionnaire designed to capture satisfaction with bisphosphonate treatment. It comprises four domains: convenience (questions 1 - 6), quality of life (questions 7 and 8), overall satisfaction (questions 9 and 10), and side effects (questions 11 - 16). Satisfaction with treatment was assessed using the OPSAT-Q composite satisfaction score, which was the average of the scores from the four domains of the OPSAT-Q converted to a 0 - 100-point scale. Higher scores indicated greater treatment satisfaction. A score of 80 or more was considered as high score.
Time Frame	At Month 6

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for this outcome.

Arm/Group Title	BMF Participants	No BMF Participants
Arm/Group Description	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants, in this arm, received BMF at Month 3. BMF was given in terms of providing serum CTX level at Month 3. A "BMF-form" was provided to the physicians to allow offering the bone marker result in an easy way. Participants were informed that their results were within or outside of the desired range. In addition, participants were also supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants were supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.
Measure Participants	328	336
Number [percentage of participants]	87.72 24.8%	87.62 24.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMF Participants, No BMF Participants
	Comments	Statistical analysis was done to compare the participant satisfaction between the Biofeedback and No-feedback arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.8989
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Percentage of Participants With Osteoporosis Patient Perception Survey (OPPS) and Osteoporosis Medical Care Satisfaction Questionnaire (OMSQ) Composite Satisfaction High Score
Description	OPPS: A standardized 6-item satisfaction questionnaire for osteoporosis medical care and treatment received during the study. Individual item score was transformed and converted to a 0 to 100 scale where higher score indicated greater satisfaction. The composite score was the average of individual item scores (transformed) and ranged from 0 to 100, where higher scores indicated greater satisfaction. OMSQ: A standardized 18-item satisfaction questionnaire for osteoporosis medical care, treatment received and blood test and their results during the study. Individual item score was transformed and converted to a 0 to 100 scale where higher score indicated greater satisfaction. The composite score was the average of individual item scores (transformed) and ranged from 0 to 100, where higher scores indicated greater satisfaction.
Time Frame	At Month 6

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for this outcome.

Arm/Group Title	BMF Participants	No BMF Participants
Arm/Group Description	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants, in this arm, received BMF at Month 3. BMF was given in terms of providing serum CTX level at Month 3. A "BMF-form" was provided to the physicians to allow offering the bone marker result in an easy way. Participants were informed that their results were within or outside of the desired range. In addition, participants were also supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants were supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.
Measure Participants	328	334
Number [percentage of participants]	74.9 21.2%	72.2 20.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMF Participants, No BMF Participants
	Comments	Statistical analysis was done to compare the participant perception between the Biofeedback and No-feedback arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.453
	Comments
	Method	ANOVA
	Comments

4. Secondary Outcome

Title	Percent Change From Baseline in CTX Based on Adherence to Ibandronate
Description	Serum CTX, a biochemical marker of bone resorption, was assessed for all participants at baseline and at final visit (Month 6). The sampling was done at the same time of the day each time to overcome the effect of circadian fluctuations. Participants were considered adherent to treatment if they took at least 83% of their assigned medications (5 of the 6 monthly ibandronate tablets) within the -1 to +21 days of their osteoporosis treatment date each month. Participant adherence was assessed by maintaining records of 'drug dispensed' and 'drug returned' on CRF and participant's self-report on Visit 2 (Month 3) and final study visit (Month 6). A drug dispensing log was maintained by the investigator. Participants were instructed at the baseline visit and Visit 2 to save and return unused or partially used medication packages on Visit 2 and final study visit, respectively.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for this outcome and "n" represents number of participants analyzed for the specified category.

Arm/Group Title	BMF Participants	No BMF Participants
Arm/Group Description	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants, in this arm, received BMF at Month 3. BMF was given in terms of providing serum CTX level at Month 3. A "BMF-form" was provided to the physicians to allow offering the bone marker result in an easy way. Participants were informed that their results were within or outside of the desired range. In addition, participants were also supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants were supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.
Measure Participants	280	287
Adherence-Yes (n=279, 281)	-47.5	-47.5
Adherence-No (n=1, 6)	-71.74	-25.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMF Participants, No BMF Participants
	Comments	Statistical analysis was done to compare the effect of adherence (Yes/No) on percent change from baseline in CTX between the Biofeedback and No-feedback arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.4917
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	15-30 days after final visit (final visit=up to 6 months)
Arm/Group Title	BMF Participants		No BMF Participants
Arm/Group Description	Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants, in this arm, received BMF at Month 3. BMF was given in terms of providing serum CTX level at Month 3. A "BMF-form" was provided to the physicians to allow offering the bone marker result in an easy way. Participants were informed that their results were within or outside of the desired range. In addition, participants were also supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.		Postmenopausal women received ibandronate 150 mg QM orally for 6 months. Participants were supported by PRP, carried out by supplying alarm devices, specifically designed to support the participant's regular drug intake.
All Cause Mortality
	BMF Participants		No BMF Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	BMF Participants		No BMF Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/354 (2.3%)		5/357 (1.4%)
Cardiac disorders
Cardiac arrest	1/354 (0.3%)		0/357 (0%)
Sinus arrhythmia	1/354 (0.3%)		0/357 (0%)
Myocardial infarction	0/354 (0%)		1/357 (0.3%)
Gastrointestinal disorders
Colitis ulcerative	0/354 (0%)		1/357 (0.3%)
General disorders
Sudden death	1/354 (0.3%)		0/357 (0%)
Infections and infestations
Appendicitis	1/354 (0.3%)		0/357 (0%)
Pneumonia	1/354 (0.3%)		0/357 (0%)
Hepatitis C	0/354 (0%)		1/357 (0.3%)
Musculoskeletal and connective tissue disorders
Osteonecrosis	0/354 (0%)		1/357 (0.3%)
Nervous system disorders
Headache	1/354 (0.3%)		0/357 (0%)
Vascular encephalopathy	1/354 (0.3%)		0/357 (0%)
Loss of consciousness	0/354 (0%)		1/357 (0.3%)
Surgical and medical procedures
Cholecystectomy	1/354 (0.3%)		0/357 (0%)
Other (Not Including Serious) Adverse Events
	BMF Participants		No BMF Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	196/354 (55.4%)		224/357 (62.7%)
Blood and lymphatic system disorders
Anaemia	0/354 (0%)		2/357 (0.6%)
Thrombocytopenia	1/354 (0.3%)		0/357 (0%)
Cardiac disorders
Palpitations	1/354 (0.3%)		0/357 (0%)
Tachycardia	3/354 (0.8%)		0/357 (0%)
Tricuspid valve disease	1/354 (0.3%)		0/357 (0%)
Ear and labyrinth disorders
Vertigo	2/354 (0.6%)		1/357 (0.3%)
Eye disorders
Cataract	0/354 (0%)		1/357 (0.3%)
Conjunctival hyperaemia	0/354 (0%)		1/357 (0.3%)
Eye pain	1/354 (0.3%)		0/357 (0%)
Keratopathy	0/354 (0%)		1/357 (0.3%)
Visual impairment	1/354 (0.3%)		0/357 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/354 (0.3%)		0/357 (0%)
Abdominal pain	6/354 (1.7%)		4/357 (1.1%)
Abdominal pain upper	5/354 (1.4%)		9/357 (2.5%)
Abnormal faeces	0/354 (0%)		1/357 (0.3%)
Constipation	1/354 (0.3%)		1/357 (0.3%)
Diarrhoea	9/354 (2.5%)		12/357 (3.4%)
Diverticulum intestinal	0/354 (0%)		1/357 (0.3%)
Dry mouth	0/354 (0%)		1/357 (0.3%)
Dyspepsia	4/354 (1.1%)		10/357 (2.8%)
Epigastric discomfort	1/354 (0.3%)		0/357 (0%)
Gastritis	2/354 (0.6%)		1/357 (0.3%)
Gastritis erosive	0/354 (0%)		1/357 (0.3%)
Gastrooesophageal reflux disease	2/354 (0.6%)		2/357 (0.6%)
Glossitis	0/354 (0%)		1/357 (0.3%)
Glossodynia	0/354 (0%)		2/357 (0.6%)
Haemorrhoidal haemorrhage	0/354 (0%)		1/357 (0.3%)
Haemorrhoids	0/354 (0%)		1/357 (0.3%)
Nausea	10/354 (2.8%)		5/357 (1.4%)
Oesophagitis	0/354 (0%)		1/357 (0.3%)
Oral discomfort	1/354 (0.3%)		0/357 (0%)
Pancreatic disorder	1/354 (0.3%)		0/357 (0%)
Pancreatitis chronic	0/354 (0%)		1/357 (0.3%)
Toothache	0/354 (0%)		1/357 (0.3%)
Vomiting	1/354 (0.3%)		1/357 (0.3%)
General disorders
Acute phase reaction	1/354 (0.3%)		0/357 (0%)
Asthenia	0/354 (0%)		1/357 (0.3%)
Chest pain	1/354 (0.3%)		1/357 (0.3%)
Chills	1/354 (0.3%)		1/357 (0.3%)
Fatigue	0/354 (0%)		2/357 (0.6%)
Hyperthermia	0/354 (0%)		1/357 (0.3%)
Influenza like illness	4/354 (1.1%)		1/357 (0.3%)
Malaise	1/354 (0.3%)		1/357 (0.3%)
Pyrexia	2/354 (0.6%)		0/357 (0%)
Hepatobiliary disorders
Biliary colic	0/354 (0%)		2/357 (0.6%)
Hepatic pain	1/354 (0.3%)		0/357 (0%)
Immune system disorders
Food allergy	1/354 (0.3%)		0/357 (0%)
Infections and infestations
Abscess	0/354 (0%)		1/357 (0.3%)
Bronchitis	3/354 (0.8%)		5/357 (1.4%)
Cellulitis	0/354 (0%)		1/357 (0.3%)
Conjunctivitis	1/354 (0.3%)		0/357 (0%)
Cystitis	5/354 (1.4%)		3/357 (0.8%)
Fungal infection	0/354 (0%)		1/357 (0.3%)
Gastroenteritis	0/354 (0%)		1/357 (0.3%)
Herpes zoster	2/354 (0.6%)		0/357 (0%)
Influenza	3/354 (0.8%)		4/357 (1.1%)
Nasopharyngitis	6/354 (1.7%)		10/357 (2.8%)
Otitis media	0/354 (0%)		1/357 (0.3%)
Pharyngitis	3/354 (0.8%)		4/357 (1.1%)
Pneumonia	0/354 (0%)		2/357 (0.6%)
Pyelonephritis	1/354 (0.3%)		0/357 (0%)
Respiratory tract infection	1/354 (0.3%)		1/357 (0.3%)
Respiratory tract infection viral	0/354 (0%)		1/357 (0.3%)
Sinusitis	0/354 (0%)		2/357 (0.6%)
Upper respiratory tract infection	1/354 (0.3%)		1/357 (0.3%)
Urinary tract infection	6/354 (1.7%)		4/357 (1.1%)
Viral infection	0/354 (0%)		2/357 (0.6%)
Viral upper respiratory tract infection	0/354 (0%)		1/357 (0.3%)
Injury, poisoning and procedural complications
Burn oesophageal	1/354 (0.3%)		0/357 (0%)
Forearm fracture	2/354 (0.6%)		0/357 (0%)
Fracture	2/354 (0.6%)		1/357 (0.3%)
Humerus fracture	0/354 (0%)		1/357 (0.3%)
Ligament sprain	3/354 (0.8%)		1/357 (0.3%)
Limb injury	0/354 (0%)		1/357 (0.3%)
Lower limb fracture	0/354 (0%)		1/357 (0.3%)
Near drowning	1/354 (0.3%)		0/357 (0%)
Wound haemorrhage	0/354 (0%)		1/357 (0.3%)
Wrist fracture	0/354 (0%)		1/357 (0.3%)
Investigations
Blood creatinine increased	1/354 (0.3%)		1/357 (0.3%)
Blood glucose increased	2/354 (0.6%)		1/357 (0.3%)
Blood phosphorus decreased	0/354 (0%)		1/357 (0.3%)
Blood potassium decreased	0/354 (0%)		1/357 (0.3%)
Laboratory test abnormal	1/354 (0.3%)		0/357 (0%)
Urine output increased	1/354 (0.3%)		0/357 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	1/354 (0.3%)		0/357 (0%)
Dyslipidaemia	1/354 (0.3%)		0/357 (0%)
Gout	0/354 (0%)		1/357 (0.3%)
Hypercholesterolaemia	0/354 (0%)		1/357 (0.3%)
Hyperglycaemia	1/354 (0.3%)		1/357 (0.3%)
Hyperlipidaemia	1/354 (0.3%)		0/357 (0%)
Hypocalcaemia	1/354 (0.3%)		2/357 (0.6%)
Hypophosphataemia	0/354 (0%)		1/357 (0.3%)
Lipid metabolism disorder	0/354 (0%)		1/357 (0.3%)
Metabolic disorder	1/354 (0.3%)		0/357 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	11/354 (3.1%)		11/357 (3.1%)
Arthritis	1/354 (0.3%)		0/357 (0%)
Back pain	8/354 (2.3%)		13/357 (3.6%)
Bone pain	3/354 (0.8%)		3/357 (0.8%)
Joint stiffness	0/354 (0%)		1/357 (0.3%)
Metatarsalgia	1/354 (0.3%)		0/357 (0%)
Muscular weakness	1/354 (0.3%)		0/357 (0%)
Musculoskeletal chest pain	0/354 (0%)		1/357 (0.3%)
Musculoskeletal pain	3/354 (0.8%)		4/357 (1.1%)
Myalgia	2/354 (0.6%)		7/357 (2%)
Neck pain	1/354 (0.3%)		3/357 (0.8%)
Osteoarthritis	1/354 (0.3%)		2/357 (0.6%)
Osteochondrosis	1/354 (0.3%)		1/357 (0.3%)
Pain in extremity	5/354 (1.4%)		1/357 (0.3%)
Pain in jaw	2/354 (0.6%)		2/357 (0.6%)
Spinal osteoarthritis	0/354 (0%)		1/357 (0.3%)
Nervous system disorders
Cerebral infarction	1/354 (0.3%)		0/357 (0%)
Cerebrovascular disorder	0/354 (0%)		1/357 (0.3%)
Cervicobrachial syndrome	1/354 (0.3%)		0/357 (0%)
Disturbance in attention	1/354 (0.3%)		0/357 (0%)
Dizziness	1/354 (0.3%)		1/357 (0.3%)
Dysgeusia	1/354 (0.3%)		1/357 (0.3%)
Headache	4/354 (1.1%)		7/357 (2%)
Migraine	0/354 (0%)		1/357 (0.3%)
Neuralgia	0/354 (0%)		1/357 (0.3%)
Paraesthesia	1/354 (0.3%)		0/357 (0%)
Polyneuropathy	0/354 (0%)		1/357 (0.3%)
Somnolence	0/354 (0%)		1/357 (0.3%)
Vertebrobasilar insufficiency	0/354 (0%)		1/357 (0.3%)
Psychiatric disorders
Anxiety disorder	1/354 (0.3%)		0/357 (0%)
Depression	1/354 (0.3%)		1/357 (0.3%)
Hallucination	0/354 (0%)		1/357 (0.3%)
Insomnia	1/354 (0.3%)		1/357 (0.3%)
Panic disorder	1/354 (0.3%)		1/357 (0.3%)
Renal and urinary disorders
Calculus urinary	2/354 (0.6%)		0/357 (0%)
Dysuria	1/354 (0.3%)		0/357 (0%)
Renal colic	0/354 (0%)		1/357 (0.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/354 (0%)		1/357 (0.3%)
Cough	0/354 (0%)		1/357 (0.3%)
Dyspnoea	1/354 (0.3%)		1/357 (0.3%)
Interstitial lung disease	1/354 (0.3%)		0/357 (0%)
Laryngeal pain	2/354 (0.6%)		0/357 (0%)
Lung disorder	1/354 (0.3%)		0/357 (0%)
Rhinitis allergic	0/354 (0%)		1/357 (0.3%)
Throat irritation	1/354 (0.3%)		0/357 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/354 (0.3%)		1/357 (0.3%)
Dermatitis	1/354 (0.3%)		0/357 (0%)
Dermatitis allergic	1/354 (0.3%)		0/357 (0%)
Pruritus	1/354 (0.3%)		1/357 (0.3%)
Rash	1/354 (0.3%)		1/357 (0.3%)
Urticaria	0/354 (0%)		1/357 (0.3%)
Surgical and medical procedures
Glaucoma surgery	0/354 (0%)		1/357 (0.3%)
Hip arthroplasty	0/354 (0%)		1/357 (0.3%)
Hysterectomy	1/354 (0.3%)		0/357 (0%)
Tooth extraction	1/354 (0.3%)		1/357 (0.3%)
Vascular disorders
Arteriosclerosis	2/354 (0.6%)		0/357 (0%)
Hypertension	4/354 (1.1%)		4/357 (1.1%)
Labile blood pressure	0/354 (0%)		1/357 (0.3%)
Orthostatic hypotension	1/354 (0.3%)		0/357 (0%)
Phlebitis	0/354 (0%)		1/357 (0.3%)
Varicose vein	1/354 (0.3%)		0/357 (0%)
Venous thrombosis	0/354 (0%)		1/357 (0.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.