Effects of Zoledronic Acid and Raloxifene on Bone Turnover Markers in Postmenopausal Women With Low Bone Mineral Density

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00431444
• Collaborator: (none)
• Enrollment: 110
• Locations: 17
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will compare the effects of Zoledronic acid and Raloxifene in reducing bone turnover markers in postmenopausal women with low bone mineral density over 6 months.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: Raloxifene; Drug: Zoledronic acid; Drug: Placebo oral pills; Drug: Placebo intravenous (i.v.) infusion	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blind, Double-dummy Study in Postmenopausal Women With Low Bone Mineral Density to Compare the Effects of a Single Dose of i.v. Zoledronic Acid 5 mg, With Daily Oral Raloxifene 60 mg OD on Bone Turnover Markers
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Zoledronic Acid Zoledronic acid 5 mg (single i.v. infusion) + daily oral placebo for 6 months (zoledronic acid group)	Drug: Zoledronic acid; Other Names: Reclast, Aclasta ; Drug: Placebo oral pills
Active Comparator: Raloxifene Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)	Drug: Raloxifene; Drug: Placebo intravenous (i.v.) infusion

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Urine N-telopeptide of Type 1 Collagen (NTx.) [Baseline and 6 months]

   The primary efficacy variable was the change from baseline in urine NTx (corrected by creatinine). The primary analysis time point was at 6 months of treatment. The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.

Secondary Outcome Measures

1. Change From Baseline in Urine NTx at 2 Months [Baseline and 2 months]

   The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.

2. Change From Baseline in Urine NTx at 4 Months [Baseline and 4 months]

   The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.

3. Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 2 Months [Baseline and 2 months]

4. Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 4 Months [Baseline and 4 months]

5. Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 6 Months [Baseline and 6 months]

6. Overall Principal Investigator Satisfaction Assessed by Satisfaction Questionnaire [Immediately after infusion procedure]

   The investigator was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."

7. Overall Nurse Satisfaction Assessed by Satisfaction Questionnaire [Immediately after infusion procedure]

   The study coordinator (nurse) was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."

8. Overall Patient Satisfaction Assessed by Satisfaction Questionnaire [Immediately after infusion procedure]

   Patients were asked to complete the satisfaction questionnaire at baseline. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."

9. Patient Preference at 6 Months for Annual i.v Therapy or Daily Oral Regimens [At 6 month visit]

   At the end-of-study visit, Month 6, patients were asked to complete a questionnaire to assess preference for the different treatment modalities (annual i.v. infusion vs. daily oral capsule). The possible answers to question were: "once a year i.v. infusion," "once daily pill," or "both are equal."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females, between 45 and 80 years (inclusive) of age, considered post-menopausal according to one of the following guidelines:

• Cessation of menses for 18 months in women < 50 years of age

• Cessation of menses for 12 months in women age 50 years or over

• Documented bilateral oophorectomy at least 1 year previously

• Documented T score of less than or equal to -1.5 on dual energy X-ray absorptiometry (DXA) scan at the lumbar spine, total hip or femoral neck within 24 months prior to screening, and clinically indicated for treatment with bisphosphonates (BPs) for osteopenia or osteoporosis

• Signed informed consent prior to initiation of any study procedure

Exclusion Criteria:

• Prior treatment with i.v. bisphosphonates within the last 2 years

• Previous use of oral bisphosphonates within the past 2 years (unless used for less than 8 weeks*).

• *NOTE: If used less than 8 weeks, the washout period is 6 months.

• Treatment with raloxifene, calcitonin, tibolone or hormone replacement therapy. The washout period for these medications is 6 months prior to randomization.

• Any treatment with strontium renalate, sodium fluoride or parathyroid hormone

• Use of systemic high dose corticosteroids at an average dose of ≥ 7.5 mg per day of oral prednisone or equivalent for a period of three months or more within the previous year

• Treatment with any investigational drug within 30 days prior to randomization

• Any woman of child bearing potential

• Patients with fractures occurring within three months prior to randomization

• History of hypersensitivity to bisphosphonates

• History of non-traumatic uveitis or iritis, within 2 years prior to study entry.

• A history of invasive malignancy of any organ system, treated or untreated, within the past 12 months prior to screening; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, Ductal Carcinoma in-situ (DCIS) that has been surgically removed, and Carcinoma in-situ (CIS) of the uterine cervix that has been surgically removed.

• Previous major solid organ transplant recipient or on a transplant waiting list

• History of hyperparathyroidism, hypoparathyroidism, Osteogenesis imperfecta, Paget's disease or any metabolic bone disease other than osteoporosis

• Any medical condition which would interfere with the action of the study drug or limit life expectancy to less than 6 months

• Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial

• Active dental infection, unhealed dental extraction or planned oral surgery within 3 month prior to randomization.

• Calculated creatinine clearance < 30 mL/min

• Greater than 2+ protein on urine dipstick without evidence of contamination or bacteriuria (may be repeated one time, at least a day apart).

• Serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.08 mmol/L (8.3 mg/dL) at screening

• AST, ALT or serum alkaline phosphatase greater than twice the upper limit of normal

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Women's Health Research	Phoenix	Arizona	United States	85015
2	Associated Pharma Research Center	Buena Park	California	United States	90620
3		Washington	District of Columbia	United States	20036
4	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
5	Women's Physicians of Jacksonville	Jacksonville	Florida	United States	32256
6	Tampa Clinical Research	Tampa	Florida	United States	33624
7	Springfield Clinic	Springfield	Illinois	United States	62703
8	Consultants in Women's Health Care	St Louis	Missouri	United States	63131
9	Alegent Health	Omaha	Nebraska	United States	68152
10	Specialty Medical and Research Center	Pahrump	Nevada	United States	89048
11	UMDNJ-Robert Wood Johnson Medical Center	New Brunswick	New Jersey	United States	08901
12	Columbia University	New York	New York	United States	10032
13	Kernodle Clinic, Inc.	Burlington	North Carolina	United States	27215
14	The Portland Clinic	Portland	Oregon	United States	97205
15	Oregon Health and Science University	Portland	Oregon	United States	97239
16	Texas Institute for Clinical Research	Fort Worth	Texas	United States	76104
17	Valley Women's Health Clinic	Renton	Washington	United States	98055

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00431444
• Other Study ID Numbers: CZOL446HUS121
• First Posted: Feb 5, 2007
• Last Update Posted: Mar 29, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by , ,: Osteoporosis; Post-menopausal; Bone mineral density
• Additional relevant MeSH terms: Osteoporosis; Bone Diseases, Metabolic; Zoledronic Acid; Raloxifene Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Period Title: Overall Study
STARTED	56	53
COMPLETED	51	46
NOT COMPLETED	5	7

Baseline Characteristics

Arm/Group Title	Zoledronic Acid	Raloxifene	Total
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)	Total of all reporting groups
Overall Participants	56	53	109
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (6.97)	61.5 (8.20)	60.1 (7.68)
Age, Customized (participants) [Number]
Between 45 and 65 years	43 76.8%	35 66%	78 71.6%
>=65 years	13 23.2%	18 34%	31 28.4%
Sex: Female, Male (Count of Participants)
Female	56 100%	53 100%	109 100%
Male	0 0%	0 0%	0 0%
Post-menopausal (year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [year]	12.5 (8.94)	13.4 (9.17)	13.0 (9.03)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Urine N-telopeptide of Type 1 Collagen (NTx.)
Description	The primary efficacy variable was the change from baseline in urine NTx (corrected by creatinine). The primary analysis time point was at 6 months of treatment. The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable of urine N-telopeptide of Type 1 collagen (NTx).Observed cases were used, no imputation was performed.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	52	53
Baseline (n = 52, 53)	49.054 (20.4515)	44.460 (23.2789)
6 months (n = 49, 47)	23.676 (11.9152)	34.183 (16.4667)
Change from baseline to Month 6 (n= 48, 47)	-24.646 (13.9893)	-8.362 (15.3852)

2. Secondary Outcome

Title	Change From Baseline in Urine NTx at 2 Months
Description	The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.
Time Frame	Baseline and 2 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable of urine N-telopeptide of Type 1 collagen (NTx).Observed cases were used, no imputation was performed.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	54	53
Baseline (n= 52, 53)	49.054 (20.4515)	44.460 (23.2789)
At Month 2 (n= 54, 50)	17.774 (9.1107)	40.756 (23.3700)
Change from baseline to Month 2 (n= 52, 50)	-31.065 (16.4960)	-4.000 (11.2757)

3. Secondary Outcome

Title	Change From Baseline in Urine NTx at 4 Months
Description	The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.
Time Frame	Baseline and 4 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable of urine N-telopeptide of Type 1 collagen (NTx).Observed cases were used, no imputation was performed.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	52	53
Baseline (n= 52 , 53)	49.054 (20.4515)	44.460 (23.2789)
At Month 4 (n= 48, 46)	20.802 (13.1632)	38.143 (24.9307)
Change from baseline to Month 4 (n= 47, 46)	-27.832 (15.4142)	-3.920 (17.1348)

4. Secondary Outcome

Title	Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 2 Months
Time Frame	Baseline and 2 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable of urine N-telopeptide of Type 1 collagen (NTx).Observed cases were used, no imputation was performed.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	51	51
Baseline (n= 50, 48)	30.104 (10.8868)	27.094 (9.4039)
At Month 2 (n= 51, 51)	20.855 (5.8499)	26.424 (7.8699)
Change from baseline to Month 2 (n= 47, 46)	-8.947 (6.4181)	-1.085 (4.0969)

5. Secondary Outcome

Title	Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 4 Months
Time Frame	Baseline and 4 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable of urine N-telopeptide of Type 1 collagen (NTx).Observed cases were used, no imputation was performed.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	50	48
Baseline (n= 50, 48)	30.104 (10.8868)	27.094 (9.4039)
At Month 4 (n= 49, 47)	18.218 (5.1846)	25.111 (8.4530)
Change from baseline to Month 4 (n= 45, 42)	-11.442 (7.8097)	-2.000 (5.0356)

6. Secondary Outcome

Title	Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 6 Months
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable of urine N-telopeptide of Type 1 collagen (NTx).Observed cases were used, no imputation was performed.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	51	48
Baseline (n= 50, 48)	30.104 (10.8868)	27.094 (9.4039)
At Month 6 (n= 51, 47)	19.237 (5.5181)	24.981 (7.9932)
Change from baseline to Month 6 (n= 47, 42)	-10.572 (7.3263)	-2.250 (7.1307)

7. Secondary Outcome

Title	Overall Principal Investigator Satisfaction Assessed by Satisfaction Questionnaire
Description	The investigator was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."
Time Frame	Immediately after infusion procedure

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) population.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	54	53
Not at all / A little	0 0%	0 0%
Somewhat	3 5.4%	1 1.9%
Quite	2 3.6%	3 5.7%
Completely	16 28.6%	11 20.8%
Missing	33 58.9%	38 71.7%

8. Secondary Outcome

Title	Overall Nurse Satisfaction Assessed by Satisfaction Questionnaire
Description	The study coordinator (nurse) was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."
Time Frame	Immediately after infusion procedure

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) population.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	54	53
Not at all / A little / Somewhat	0 0%	0 0%
Quite	4 7.1%	3 5.7%
Completely	29 51.8%	35 66%
Missing	21 37.5%	15 28.3%

9. Secondary Outcome

Title	Overall Patient Satisfaction Assessed by Satisfaction Questionnaire
Description	Patients were asked to complete the satisfaction questionnaire at baseline. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."
Time Frame	Immediately after infusion procedure

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) population.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	54	53
Not at all	1 1.8%	1 1.9%
A little	0 0%	1 1.9%
Somewhat	1 1.8%	1 1.9%
Quite	9 16.1%	7 13.2%
Completely	43 76.8%	42 79.2%
Missing	0 0%	1 1.9%

10. Secondary Outcome

Title	Patient Preference at 6 Months for Annual i.v Therapy or Daily Oral Regimens
Description	At the end-of-study visit, Month 6, patients were asked to complete a questionnaire to assess preference for the different treatment modalities (annual i.v. infusion vs. daily oral capsule). The possible answers to question were: "once a year i.v. infusion," "once daily pill," or "both are equal."
Time Frame	At 6 month visit

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) population.

Arm/Group Title	Zoledronic Acid	Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)	Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Measure Participants	54	53
Once a year intravenous infusion	47 83.9%	46 86.8%
Once daily pill	3 5.4%	4 7.5%
Both are equal	3 5.4%	3 5.7%
Missing	1 1.8%	0 0%

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	The safety population included all randomized patients who received at least one dose of study drug.
Arm/Group Title	Zoledronic Acid		Raloxifene
Arm/Group Description	Zoledronic acid 5 mg (single intravenous (i.v.) infusion) + daily oral placebo for 6 months (zoledronic acid group)		Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
All Cause Mortality
	Zoledronic Acid		Raloxifene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Zoledronic Acid		Raloxifene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/56 (1.8%)		1/53 (1.9%)
Gastrointestinal disorders
Gastric ulcer haemorrhage	0/56 (0%)		1/53 (1.9%)
Infections and infestations
Herpes zoster	1/56 (1.8%)		0/53 (0%)
Other (Not Including Serious) Adverse Events
	Zoledronic Acid		Raloxifene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/56 (55.4%)		13/53 (24.5%)
Gastrointestinal disorders
Constipation	1/56 (1.8%)		3/53 (5.7%)
Diarrhoea	5/56 (8.9%)		1/53 (1.9%)
Nausea	7/56 (12.5%)		1/53 (1.9%)
General disorders
Chills	3/56 (5.4%)		1/53 (1.9%)
Fatigue	3/56 (5.4%)		1/53 (1.9%)
Influenza like illness	3/56 (5.4%)		0/53 (0%)
Pain	4/56 (7.1%)		0/53 (0%)
Pyrexia	6/56 (10.7%)		0/53 (0%)
Infections and infestations
Sinusitis	4/56 (7.1%)		4/53 (7.5%)
Urinary tract infection	4/56 (7.1%)		2/53 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/56 (7.1%)		2/53 (3.8%)
Back pain	3/56 (5.4%)		0/53 (0%)
Myalgia	4/56 (7.1%)		3/53 (5.7%)
Nervous system disorders
Headache	3/56 (5.4%)		0/53 (0%)
Vascular disorders
Hypertension	3/56 (5.4%)		0/53 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.