Atacicept in Anti-Tumor Necrosis Factor Alpha-naïve Subjects With Rheumatoid Arthritis (AUGUST II)

• Sponsor: EMD Serono (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00595413
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 311
• Locations: 2
• Arms: 4
• Duration (Months): 25
• Patients Per Site: 155.5
• Patients Per Site Per Month: 6.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of atacicept compared to placebo in the treatment of signs and symptoms in a subject population with active rheumatoid arthritis (RA), inadequate response to methotrexate (MTX) and no previous exposure to anti-tumor necrosis factor alpha (anti-TNFalpha) therapy.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Placebo matched to atacicept; Drug: Atacicept: with loading dose; Drug: Atacicept; Biological: Adalimumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 311 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Placebo Controlled, Multi-centre Phase II Study of Atacicept in Anti-TNFα-naïve Patients With Moderate to Severely Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atacicept 150 mg with loading dose	Drug: Atacicept: with loading dose; Atacicept will be administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.
Experimental: Atacicept 150 mg without loading dose	Drug: Atacicept; Atacicept will be administered subcutaneously at a dose of 150 mg once a week for 25 weeks.
Active Comparator: Adalimumab	Biological: Adalimumab; Adalimumab (Humira®) will be administered subcutaneously at a dose of 40 mg every other week for 25 weeks.; Other Names: Humira®
Placebo Comparator: Placebo	Drug: Placebo matched to atacicept; Placebo matched to atacicept will be administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26 [Week 26]

   ACR20-CRP response is defined as greater than or equal to (>=) 20 percent (%) improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=20% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).

Secondary Outcome Measures

1. Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26 [Week 26]

   ACR50-CRP response is defined as >=50% improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=50% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).

2. Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26 [Week 26]

   ACR70-CRP response is defined as >=70% improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=70% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).

3. Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 26 [Week 26]

   The EULAR response criteria evaluate change in DAS28 scores represented as "good response", "moderate response", or "no response" considering both the current DAS28 score and the observed improvement from baseline. Participants were considered to have "good" or "moderate" EULAR response if at the time of assessment, their DAS28 score was less than or equal to (<=) 5.1 and the improvement from baseline in their DAS28 score was greater than (>) 0.6; or if at the time of assessment, their DAS28 score was >5.1 and improvement from baseline in their DAS28 score was >1.2.

4. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs [From the first dose of study drug up to 30 days after the last dose of study drug, assessed up to Week 38]

   An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female subjects greater than or equal to (>=) 18 years of age at the time of informed consent who have RA satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 6 months

• Subjects must have active disease, defined by >=8 swollen joints (out of 66), >=8 tender joints (out of 68) and CRP >=10 milligram per liter (mg/L) and/or erythrocyte sedimentation rate (ESR) >=28 millimeter per hour (mm/hr), despite treatment with MTX at a dose of >=15 milligram per week (mg/week) for greater than (>) 3 months

• Other protocol-defined inclusion criteria could apply

Exclusion Criteria:

• Inflammatory joint disease other than RA

• Previous or concurrent treatment with any approved or investigational biological compound for RA, including but not restricted to any anti-TNFalpha agents, rituximab, abatacept, tocilizumab, interleukin-1 receptor antagonist (IL-1Ra) and belimumab

• Treatment with disease-modifying anti-rheumatic drug (DMARDs) other than MTX

• Participation in any interventional clinical trial within 1 month before study Day 1

• MTX dose >25 mg/week, prednisone dose >10 mg/day (or equivalent), or change in steroid or non-steroidal anti-inflammatory drug (NSAID) dosing regimen within 28 days before study Day 1

• Immunization with live vaccine or immunoglobulin (Ig) treatment within 28 days before study Day 1 or need for such treatment during the study (including follow-up)

• Any history or presence of active or latent tuberculosis, major infection requiring hospitalization or intravenous anti-infectives within 28 days before study Day 1

• Other major concurrent illness or organ dysfunction as specified in the protocol

• Serum IgG below 6 gram per liter (g/L)

• Known hypersensitivity to atacicept or to any of the components of the formulated atacicept

• Other protocol-defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Please Contact US Medical Information	Rockland	Massachusetts	United States
2	Please contact the Merck KGaA Communication Center	Darmstadt		Germany

Sponsors and Collaborators

• EMD Serono
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck Serono International SA, an affiliate of Merck KGaA Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The European League Against Rheumatism (EULAR)

Publications

None provided.

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT00595413
• Other Study ID Numbers: 27905; 2007-002536-29
• First Posted: Jan 16, 2008
• Last Update Posted: Feb 17, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by EMD Serono: Rheumatoid arthritis; Atacicept; Adalimumab; Humira®
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Adalimumab

Study Results

Participant Flow

Arm/Group Title	Placebo	Atacicept 150 mg With Loading Dose	Atacicept 150 mg Without Loading Dose	Adalimumab
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg once a week for 25 weeks. Participants also received placebo matched to atacicept subcutaneously once a week during initial 4 weeks for blinding purpose (placebo injections alternating with atacicept injections).	Adalimumab (Humira®) was administered subcutaneously at a dose of 40 mg every other week for 25 weeks.
Period Title: Overall Study
STARTED	76	78	78	79
COMPLETED	69	73	70	75
NOT COMPLETED	7	5	8	4

Baseline Characteristics

Arm/Group Title	Placebo	Atacicept 150 mg With Loading Dose	Atacicept 150 mg Without Loading Dose	Adalimumab	Total
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg once a week for 25 weeks. Participants also received placebo matched to atacicept subcutaneously once a week during initial 4 weeks for blinding purpose (placebo injections alternating with atacicept injections).	Adalimumab (Humira®) was administered subcutaneously at a dose of 40 mg every other week for 25 weeks.	Total of all reporting groups
Overall Participants	76	78	78	79	311
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.0 (10.3)	53.0 (11.3)	53.3 (13.2)	53.3 (11.5)	53.4 (11.6)
Sex: Female, Male (Count of Participants)
Female	64 84.2%	65 83.3%	66 84.6%	64 81%	259 83.3%
Male	12 15.8%	13 16.7%	12 15.4%	15 19%	52 16.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26
Description	ACR20-CRP response is defined as greater than or equal to (>=) 20 percent (%) improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=20% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 study treatment dose.

Arm/Group Title	Placebo	Atacicept 150 mg With Loading Dose	Atacicept 150 mg Without Loading Dose	Adalimumab
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg once a week for 25 weeks. Participants also received placebo matched to atacicept subcutaneously once a week during initial 4 weeks for blinding purpose (placebo injections alternating with atacicept injections).	Adalimumab (Humira®) was administered subcutaneously at a dose of 40 mg every other week for 25 weeks.
Measure Participants	76	78	78	79
Number [percentage of participants]	46.1 60.7%	44.9 57.6%	57.7 74%	70.9 89.7%

2. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26
Description	ACR50-CRP response is defined as >=50% improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=50% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 study treatment dose.

Arm/Group Title	Placebo	Atacicept 150 mg With Loading Dose	Atacicept 150 mg Without Loading Dose	Adalimumab
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg once a week for 25 weeks. Participants also received placebo matched to atacicept subcutaneously once a week during initial 4 weeks for blinding purpose (placebo injections alternating with atacicept injections).	Adalimumab (Humira®) was administered subcutaneously at a dose of 40 mg every other week for 25 weeks.
Measure Participants	76	78	78	79
Number [percentage of participants]	14.5 19.1%	29.5 37.8%	33.3 42.7%	38.0 48.1%

3. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26
Description	ACR70-CRP response is defined as >=70% improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=70% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 study treatment dose.

Arm/Group Title	Placebo	Atacicept 150 mg With Loading Dose	Atacicept 150 mg Without Loading Dose	Adalimumab
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg once a week for 25 weeks. Participants also received placebo matched to atacicept subcutaneously once a week during initial 4 weeks for blinding purpose (placebo injections alternating with atacicept injections).	Adalimumab (Humira®) was administered subcutaneously at a dose of 40 mg every other week for 25 weeks.
Measure Participants	76	78	78	79
Number [percentage of participants]	5.3 7%	12.8 16.4%	12.8 16.4%	17.7 22.4%

4. Secondary Outcome

Title	Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 26
Description	The EULAR response criteria evaluate change in DAS28 scores represented as "good response", "moderate response", or "no response" considering both the current DAS28 score and the observed improvement from baseline. Participants were considered to have "good" or "moderate" EULAR response if at the time of assessment, their DAS28 score was less than or equal to (<=) 5.1 and the improvement from baseline in their DAS28 score was greater than (>) 0.6; or if at the time of assessment, their DAS28 score was >5.1 and improvement from baseline in their DAS28 score was >1.2.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 study treatment dose.

Arm/Group Title	Placebo	Atacicept 150 mg With Loading Dose	Atacicept 150 mg Without Loading Dose	Adalimumab
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg once a week for 25 weeks. Participants also received placebo matched to atacicept subcutaneously once a week during initial 4 weeks for blinding purpose (placebo injections alternating with atacicept injections).	Adalimumab (Humira®) was administered subcutaneously at a dose of 40 mg every other week for 25 weeks.
Measure Participants	76	78	78	79
Number [percentage of participants]	59.2 77.9%	64.1 82.2%	67.9 87.1%	81.0 102.5%

5. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Description	An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Time Frame	From the first dose of study drug up to 30 days after the last dose of study drug, assessed up to Week 38

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 study treatment dose.

Arm/Group Title	Placebo	Atacicept 150 mg With Loading Dose	Atacicept 150 mg Without Loading Dose	Adalimumab
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg once a week for 25 weeks. Participants also received placebo matched to atacicept subcutaneously once a week during initial 4 weeks for blinding purpose (placebo injections alternating with atacicept injections).	Adalimumab (Humira®) was administered subcutaneously at a dose of 40 mg every other week for 25 weeks.
Measure Participants	76	78	78	79
TEAEs	38 50%	49 62.8%	49 62.8%	50 63.3%
Serious TEAEs	2 2.6%	4 5.1%	7 9%	3 3.8%

Adverse Events

Time Frame	From the first dose of study drug up to 30 days after the last dose of study drug, assessed up to Week 38
Adverse Event Reporting Description	An adverse event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.
Arm/Group Title	Placebo		Atacicept 150 mg With Loading Dose		Atacicept 150 mg Without Loading Dose		Adalimumab
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.		Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.		Atacicept was administered subcutaneously at a dose of 150 mg once a week for 25 weeks. Participants also received placebo matched to atacicept subcutaneously once a week during initial 4 weeks for blinding purpose (placebo injections alternating with atacicept injections).		Adalimumab (Humira®) was administered subcutaneously at a dose of 40 mg every other week for 25 weeks.
All Cause Mortality
	Placebo		Atacicept 150 mg With Loading Dose		Atacicept 150 mg Without Loading Dose		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Atacicept 150 mg With Loading Dose		Atacicept 150 mg Without Loading Dose		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/76 (2.6%)		4/78 (5.1%)		7/78 (9%)		3/79 (3.8%)
Cardiac disorders
Pericarditis	1/76 (1.3%)		0/78 (0%)		0/78 (0%)		0/79 (0%)
General disorders
Pyrexia	0/76 (0%)		0/78 (0%)		1/78 (1.3%)		0/79 (0%)
Sudden cardiac death	0/76 (0%)		0/78 (0%)		1/78 (1.3%)		0/79 (0%)
Infections and infestations
Pneumonia	0/76 (0%)		0/78 (0%)		0/78 (0%)		2/79 (2.5%)
Cellulitis	1/76 (1.3%)		0/78 (0%)		0/78 (0%)		0/79 (0%)
Disseminated tuberculosis	0/76 (0%)		0/78 (0%)		0/78 (0%)		1/79 (1.3%)
Injury, poisoning and procedural complications
Tendon rupture	1/76 (1.3%)		0/78 (0%)		0/78 (0%)		0/79 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/76 (0%)		1/78 (1.3%)		0/78 (0%)		0/79 (0%)
Rheumatoid arthritis	0/76 (0%)		0/78 (0%)		1/78 (1.3%)		0/79 (0%)
Spinal osteoarthritis	0/76 (0%)		0/78 (0%)		1/78 (1.3%)		0/79 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer female	0/76 (0%)		1/78 (1.3%)		0/78 (0%)		0/79 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/76 (0%)		1/78 (1.3%)		0/78 (0%)		0/79 (0%)
Pregnancy	0/76 (0%)		1/78 (1.3%)		0/78 (0%)		0/79 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/76 (0%)		0/78 (0%)		1/78 (1.3%)		0/79 (0%)
Laryngeal oedema	0/76 (0%)		1/78 (1.3%)		0/78 (0%)		0/79 (0%)
Obstructive airways disorder	0/76 (0%)		0/78 (0%)		1/78 (1.3%)		0/79 (0%)
Pulmonary embolism	0/76 (0%)		0/78 (0%)		1/78 (1.3%)		0/79 (0%)
Pulmonary hypertension	0/76 (0%)		0/78 (0%)		1/78 (1.3%)		0/79 (0%)
Surgical and medical procedures
Knee arthroplasty	0/76 (0%)		0/78 (0%)		1/78 (1.3%)		0/79 (0%)
Vascular disorders
Hypertension	0/76 (0%)		1/78 (1.3%)		0/78 (0%)		0/79 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Atacicept 150 mg With Loading Dose		Atacicept 150 mg Without Loading Dose		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/76 (30.3%)		27/78 (34.6%)		24/78 (30.8%)		22/79 (27.8%)
Blood and lymphatic system disorders
Leukopenia	4/76 (5.3%)		1/78 (1.3%)		1/78 (1.3%)		3/79 (3.8%)
General disorders
Fatigue	1/76 (1.3%)		2/78 (2.6%)		1/78 (1.3%)		4/79 (5.1%)
Infections and infestations
Bronchitis	4/76 (5.3%)		5/78 (6.4%)		6/78 (7.7%)		3/79 (3.8%)
Nasopharyngitis	6/76 (7.9%)		2/78 (2.6%)		4/78 (5.1%)		5/79 (6.3%)
Upper respiratory tract infection	2/76 (2.6%)		4/78 (5.1%)		4/78 (5.1%)		6/79 (7.6%)
Pharyngitis	1/76 (1.3%)		3/78 (3.8%)		4/78 (5.1%)		3/79 (3.8%)
Sinusitis	0/76 (0%)		5/78 (6.4%)		1/78 (1.3%)		0/79 (0%)
Urinary tract infection	3/76 (3.9%)		4/78 (5.1%)		4/78 (5.1%)		2/79 (2.5%)
Nervous system disorders
Headache	3/76 (3.9%)		4/78 (5.1%)		4/78 (5.1%)		2/79 (2.5%)
Respiratory, thoracic and mediastinal disorders
Cough	2/76 (2.6%)		3/78 (3.8%)		4/78 (5.1%)		2/79 (2.5%)
Vascular disorders
Hypertension	4/76 (5.3%)		3/78 (3.8%)		2/78 (2.6%)		1/79 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Prior to publishing results, Institution and Principal Investigator (PI) must first provide Sponsor with a copy of proposed publication for review at least 30 days prior to submission. If Institution and PI do not agree to modification, they shall so notify Sponsor and postpone submission for additional 60 days to allow Sponsor to seek legal remedies or file patent applications. There is a need for coordinated approach to any publication of results from sites for any multi-site study.