Safety, Tolerability and Efficacy of ACZ885 on Leg Artery Structure in Patients With Peripheral Artery Disease

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01731990
• Collaborator: (none)
• Enrollment: 38
• Locations: 14
• Arms: 2
• Actual Duration (Months): 45.1
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study was designed to assess the safety, tolerability and efficacy of ACZ885 on the leg artery structure and physical activity in patients with atherosclerotic peripheral artery disease and leg pain from walking.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Artery Disease	Drug: Canakinumab (ACZ885); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability and Effects on Arterial Structure and Function of ACZ885 in Patients With Intermittent Claudication.
• Actual Study Start Date: Oct 30, 2012
• Actual Primary Completion Date: Aug 4, 2016
• Actual Study Completion Date: Aug 4, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canakinumab (ACZ885) Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months	Drug: Canakinumab (ACZ885); Dosage form: solution for injection Strength: 150 mg/1 mL Mode of administration: subcutaneous use.
Placebo Comparator: Placebo Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months	Drug: Placebo; Matching placebo of Canakinumab

Outcome Measures

Primary Outcome Measures

1. Mean Vessel Wall Area Ratio of 12 Months to Baseline [Baseline, 12 months post-dose]

   Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.

Secondary Outcome Measures

1. Number of Patients With Adverse Events in 12 Months [Baseline to 12 months post-dose]

   Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death.

2. Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline [Baseline, 12 months post-dose]

   Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.

3. High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline [Baseline, 12 months post-dose]

   Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Must have a signed informed consent form.

• Must be between the ages of 18 and 85

• Must experience leg pain associated with walking and have an ankle brachial index between 0.40 and 0.9

• Must be on stable aspirin and statin doses for at least 6 weeks

• Blood pressure within ranges specified in the protocol

• Able to communicate well with the Investigator and understand and comply with the study procedures

Key Exclusion Criteria:

• Recent use of any other experimental drugs

• Pregnant or nursing women

• Women of child bearing potential unless willing to use contraception as detailed in the protocol

• Cannot walk 15 meters (50 feet)

• People on restricted medications as listed in the protocol

• Any open or non-healing wounds with 3 months of study start or infection within 2 weeks or study start

• Significant heart disease

• Uncontrolled diabetes

• Significant kidney or liver disease

• Live vaccinations within 3 months of study start

• History of untreated tuberculosis or active tuberculosis (TB)

• Patients with metal in their body (excluded due to MRI scan) as detailed in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Phoenix	Arizona	United States	85302
2	Novartis Investigative Site	Jacksonville	Florida	United States	32207
3	Novartis Investigative Site	Jacksonville	Florida	United States	32216
4	Novartis Investigative Site	Chicago	Illinois	United States	60611
5	Novartis Investigative Site	Lutherville	Maryland	United States	21093
6	Novartis Investigative Site	Columbus	Ohio	United States	43215
7	Novartis Investigative Site	Knoxville	Tennessee	United States	37920
8	Novartis Investigative Site	Richmond	Virginia	United States	23294
9	Novartis Investigative Site	Hamburg		Germany	20099
10	Novartis Investigative Site	Hamburg		Germany	22559
11	Novartis Investigative Site	Heidelberg		Germany	69120
12	Novartis Investigative Site	Mainz		Germany	55116
13	Novartis Investigative Site	München		Germany	80336
14	Novartis Investigative Site	Amman		Jordan	11941

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01731990
• Other Study ID Numbers: CACZ885M2201; 2012-001427-12
• First Posted: Nov 22, 2012
• Last Update Posted: Dec 30, 2020
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Peripheral artery disease; Intermittent claudication; magnetic resonance imaging
• Additional relevant MeSH terms: Peripheral Arterial Disease; Intermittent Claudication

Study Results

Participant Flow

Pre-assignment Detail	A total of 38 patients were enrolled into the study.

Arm/Group Title	Canakinumab (ACZ885)	Placebo
Arm/Group Description	Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months	Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months
Period Title: Overall Study
STARTED	18	20
COMPLETED	14	12
NOT COMPLETED	4	8

Baseline Characteristics

Arm/Group Title	Canakinumab (ACZ885)	Placebo	Total
Arm/Group Description	Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months	Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months	Total of all reporting groups
Overall Participants	18	20	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.0 (8.64)	63.5 (7.98)	64.7 (8.29)
Sex: Female, Male (Count of Participants)
Female	4 22.2%	7 35%	11 28.9%
Male	14 77.8%	13 65%	27 71.1%

Outcome Measures

1. Primary Outcome

Title	Mean Vessel Wall Area Ratio of 12 Months to Baseline
Description	Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
Time Frame	Baseline, 12 months post-dose

Outcome Measure Data

Analysis Population Description

The pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients who underwent iliac/femoral stenting were removed from all data points that occurred after this procedure in the analysis.

Arm/Group Title	Canakinumab (ACZ885)	Placebo
Arm/Group Description	Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months	Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months
Measure Participants	12	9
Least Squares Mean (Standard Error) [Ratio]	1.05 (0.03)	0.99 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Canakinumab (ACZ885), Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.284
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment effect for ratio to placebo
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 90%; 0.97 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Patients With Adverse Events in 12 Months
Description	Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death.
Time Frame	Baseline to 12 months post-dose

Outcome Measure Data

Analysis Population Description

All patients that received any study drug were included in the safety analysis set.

Arm/Group Title	Canakinumab (ACZ885)	Placebo
Arm/Group Description	Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months	Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months
Measure Participants	18	20
Total Adverse events	16 88.9%	20 100%
Serious Adverse events	10 55.6%	10 50%
Death	1 5.6%	0 0%

3. Secondary Outcome

Title	Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline
Description	Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
Time Frame	Baseline, 12 months post-dose

Outcome Measure Data

Analysis Population Description

The PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients with baseline and 12 month data are included in this analysis.

Arm/Group Title	Canakinumab (ACZ885)	Placebo
Arm/Group Description	Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months	Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months
Measure Participants	15	13
Least Squares Mean (Standard Error) [Ratio]	0.62 (0.12)	0.79 (0.17)

4. Secondary Outcome

Title	High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline
Description	Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
Time Frame	Baseline, 12 months post-dose

Outcome Measure Data

Analysis Population Description

The PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients with baseline and 12 month data are included in this analysis.

Arm/Group Title	Canakinumab (ACZ885)	Placebo
Arm/Group Description	Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months	Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months
Measure Participants	15	13
Least Squares Mean (Standard Error) [Ratio]	0.62 (0.14)	0.83 (0.20)

Adverse Events

Time Frame	Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
Arm/Group Title	Canakinumab (ACZ885)		Placebo
Arm/Group Description	Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months		Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months
All Cause Mortality
	Canakinumab (ACZ885)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Canakinumab (ACZ885)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/18 (55.6%)		10/20 (50%)
Cardiac disorders
Angina pectoris	1/18 (5.6%)		0/20 (0%)
Arrhythmia	0/18 (0%)		1/20 (5%)
Atrioventricular block	0/18 (0%)		1/20 (5%)
Atrioventricular block complete	1/18 (5.6%)		0/20 (0%)
Cardiac failure	0/18 (0%)		1/20 (5%)
Coronary artery disease	2/18 (11.1%)		1/20 (5%)
Myocardial infarction	1/18 (5.6%)		0/20 (0%)
Sinus bradycardia	1/18 (5.6%)		0/20 (0%)
Gastrointestinal disorders
Abdominal pain upper	1/18 (5.6%)		0/20 (0%)
Gastric ulcer	1/18 (5.6%)		0/20 (0%)
Mesenteric arterial occlusion	1/18 (5.6%)		0/20 (0%)
Mesenteric arteriosclerosis	1/18 (5.6%)		0/20 (0%)
General disorders
Chest pain	0/18 (0%)		1/20 (5%)
Non-cardiac chest pain	0/18 (0%)		2/20 (10%)
Infections and infestations
Abscess limb	1/18 (5.6%)		0/20 (0%)
Groin abscess	1/18 (5.6%)		0/20 (0%)
Helicobacter gastritis	0/18 (0%)		1/20 (5%)
Pneumonia	1/18 (5.6%)		0/20 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/18 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/18 (0%)		1/20 (5%)
Pulmonary oedema	0/18 (0%)		1/20 (5%)
Pulmonary vascular disorder	0/18 (0%)		1/20 (5%)
Vascular disorders
Peripheral arterial occlusive disease	3/18 (16.7%)		2/20 (10%)
Peripheral artery occlusion	0/18 (0%)		1/20 (5%)
Peripheral vascular disorder	0/18 (0%)		1/20 (5%)
Other (Not Including Serious) Adverse Events
	Canakinumab (ACZ885)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/18 (88.9%)		17/20 (85%)
Blood and lymphatic system disorders
Anaemia	0/18 (0%)		1/20 (5%)
Plasma cell disorder	0/18 (0%)		1/20 (5%)
Cardiac disorders
Angina pectoris	2/18 (11.1%)		1/20 (5%)
Atrioventricular block first degree	1/18 (5.6%)		0/20 (0%)
Bradycardia	2/18 (11.1%)		0/20 (0%)
Coronary artery disease	1/18 (5.6%)		0/20 (0%)
Ear and labyrinth disorders
Cerumen impaction	0/18 (0%)		1/20 (5%)
Deafness unilateral	1/18 (5.6%)		0/20 (0%)
Vertigo	1/18 (5.6%)		1/20 (5%)
Endocrine disorders
Goitre	0/18 (0%)		1/20 (5%)
Hypothyroidism	1/18 (5.6%)		0/20 (0%)
Eye disorders
Cataract	0/18 (0%)		1/20 (5%)
Gastrointestinal disorders
Abdominal pain	1/18 (5.6%)		1/20 (5%)
Abdominal pain upper	2/18 (11.1%)		2/20 (10%)
Constipation	3/18 (16.7%)		0/20 (0%)
Diarrhoea	1/18 (5.6%)		1/20 (5%)
Diverticulum	1/18 (5.6%)		0/20 (0%)
Dysphagia	0/18 (0%)		1/20 (5%)
Erosive oesophagitis	1/18 (5.6%)		0/20 (0%)
Flatulence	1/18 (5.6%)		0/20 (0%)
Gastrooesophageal reflux disease	0/18 (0%)		1/20 (5%)
Gingival bleeding	1/18 (5.6%)		0/20 (0%)
Hiatus hernia	2/18 (11.1%)		0/20 (0%)
Large intestine polyp	1/18 (5.6%)		0/20 (0%)
Nausea	3/18 (16.7%)		1/20 (5%)
Oesophageal mucosa erythema	1/18 (5.6%)		0/20 (0%)
Oesophageal stenosis	1/18 (5.6%)		0/20 (0%)
Pancreatic cyst	1/18 (5.6%)		0/20 (0%)
Rectal haemorrhage	1/18 (5.6%)		0/20 (0%)
Toothache	1/18 (5.6%)		0/20 (0%)
Vomiting	0/18 (0%)		1/20 (5%)
General disorders
Drug intolerance	1/18 (5.6%)		0/20 (0%)
Fatigue	3/18 (16.7%)		2/20 (10%)
Feeling cold	0/18 (0%)		1/20 (5%)
Influenza like illness	1/18 (5.6%)		1/20 (5%)
Multiple organ dysfunction syndrome	1/18 (5.6%)		0/20 (0%)
Oedema peripheral	0/18 (0%)		1/20 (5%)
Peripheral swelling	1/18 (5.6%)		0/20 (0%)
Infections and infestations
Bronchitis	1/18 (5.6%)		0/20 (0%)
Conjunctivitis	1/18 (5.6%)		2/20 (10%)
Conjunctivitis viral	0/18 (0%)		1/20 (5%)
Escherichia urinary tract infection	1/18 (5.6%)		0/20 (0%)
Folliculitis	1/18 (5.6%)		0/20 (0%)
Gastroenteritis	1/18 (5.6%)		0/20 (0%)
Gastroenteritis viral	1/18 (5.6%)		0/20 (0%)
Influenza	1/18 (5.6%)		1/20 (5%)
Nasopharyngitis	2/18 (11.1%)		4/20 (20%)
Otitis media	0/18 (0%)		1/20 (5%)
Respiratory tract infection viral	1/18 (5.6%)		0/20 (0%)
Tinea pedis	0/18 (0%)		1/20 (5%)
Tooth abscess	1/18 (5.6%)		0/20 (0%)
Tooth infection	0/18 (0%)		1/20 (5%)
Upper respiratory tract infection	4/18 (22.2%)		4/20 (20%)
Urinary tract infection	1/18 (5.6%)		2/20 (10%)
Vulvovaginal mycotic infection	0/18 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
Concussion	0/18 (0%)		1/20 (5%)
Contusion	0/18 (0%)		1/20 (5%)
Excoriation	0/18 (0%)		1/20 (5%)
Fall	0/18 (0%)		1/20 (5%)
Laceration	1/18 (5.6%)		1/20 (5%)
Muscle strain	1/18 (5.6%)		0/20 (0%)
Post procedural haemorrhage	1/18 (5.6%)		0/20 (0%)
Procedural pain	1/18 (5.6%)		0/20 (0%)
Soft tissue injury	1/18 (5.6%)		0/20 (0%)
Investigations
Blood creatinine increased	0/18 (0%)		1/20 (5%)
Blood pressure increased	0/18 (0%)		1/20 (5%)
Blood triglycerides increased	1/18 (5.6%)		0/20 (0%)
Oesophagogastroduodenoscopy abnormal	1/18 (5.6%)		0/20 (0%)
Platelet count decreased	0/18 (0%)		1/20 (5%)
Metabolism and nutrition disorders
Decreased appetite	1/18 (5.6%)		0/20 (0%)
Hyperglycaemia	0/18 (0%)		1/20 (5%)
Hypochloraemia	0/18 (0%)		1/20 (5%)
Hypoglycaemia	0/18 (0%)		2/20 (10%)
Hypokalaemia	0/18 (0%)		2/20 (10%)
Hyponatraemia	0/18 (0%)		1/20 (5%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/18 (27.8%)		0/20 (0%)
Back pain	2/18 (11.1%)		1/20 (5%)
Intervertebral disc degeneration	1/18 (5.6%)		0/20 (0%)
Muscle spasms	0/18 (0%)		1/20 (5%)
Musculoskeletal chest pain	1/18 (5.6%)		0/20 (0%)
Musculoskeletal pain	1/18 (5.6%)		0/20 (0%)
Myalgia	2/18 (11.1%)		1/20 (5%)
Pain in extremity	2/18 (11.1%)		1/20 (5%)
Plantar fasciitis	1/18 (5.6%)		1/20 (5%)
Nervous system disorders
Areflexia	1/18 (5.6%)		0/20 (0%)
Dizziness postural	0/18 (0%)		1/20 (5%)
Headache	1/18 (5.6%)		0/20 (0%)
Muscle contractions involuntary	0/18 (0%)		1/20 (5%)
Neuropathy peripheral	1/18 (5.6%)		0/20 (0%)
Paraesthesia	0/18 (0%)		1/20 (5%)
Sciatica	0/18 (0%)		1/20 (5%)
Psychiatric disorders
Anxiety	1/18 (5.6%)		0/20 (0%)
Insomnia	3/18 (16.7%)		1/20 (5%)
Renal and urinary disorders
Chronic kidney disease	0/18 (0%)		1/20 (5%)
Polyuria	1/18 (5.6%)		0/20 (0%)
Renal artery stenosis	0/18 (0%)		1/20 (5%)
Renal cyst	1/18 (5.6%)		0/20 (0%)
Reproductive system and breast disorders
Genital pain	0/18 (0%)		1/20 (5%)
Prostatitis	0/18 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/18 (5.6%)		0/20 (0%)
Epistaxis	0/18 (0%)		1/20 (5%)
Oropharyngeal pain	1/18 (5.6%)		0/20 (0%)
Pleural effusion	1/18 (5.6%)		0/20 (0%)
Pneumothorax	1/18 (5.6%)		0/20 (0%)
Pulmonary mass	0/18 (0%)		1/20 (5%)
Rhinitis allergic	0/18 (0%)		1/20 (5%)
Skin and subcutaneous tissue disorders
Alopecia	1/18 (5.6%)		0/20 (0%)
Blister	1/18 (5.6%)		1/20 (5%)
Dermatitis	0/18 (0%)		1/20 (5%)
Dermatitis contact	0/18 (0%)		1/20 (5%)
Drug eruption	0/18 (0%)		1/20 (5%)
Ecchymosis	0/18 (0%)		1/20 (5%)
Eczema	0/18 (0%)		1/20 (5%)
Eczema asteatotic	0/18 (0%)		1/20 (5%)
Hyperhidrosis	1/18 (5.6%)		0/20 (0%)
Hyperkeratosis	1/18 (5.6%)		1/20 (5%)
Lichen nitidus	0/18 (0%)		1/20 (5%)
Nail discolouration	0/18 (0%)		1/20 (5%)
Photosensitivity reaction	0/18 (0%)		1/20 (5%)
Rash	1/18 (5.6%)		1/20 (5%)
Skin lesion	0/18 (0%)		1/20 (5%)
Skin plaque	1/18 (5.6%)		0/20 (0%)
Vascular disorders
Aortic aneurysm	1/18 (5.6%)		0/20 (0%)
Aortic thrombosis	1/18 (5.6%)		0/20 (0%)
Hypertension	1/18 (5.6%)		2/20 (10%)
Hypotension	1/18 (5.6%)		0/20 (0%)
Intermittent claudication	1/18 (5.6%)		0/20 (0%)
Peripheral arterial occlusive disease	2/18 (11.1%)		1/20 (5%)
Peripheral ischaemia	1/18 (5.6%)		1/20 (5%)

Limitations/Caveats

Study was terminated after the third interim analysis based on result from primary outcome analysis.

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 or disclosure of trial results in their entirety.