Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy (EU Extension Study)

• Sponsor: CSL Behring (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00751621
• Collaborator: (none)
• Enrollment: 40
• Locations: 13
• Arm: 1
• Duration (Months): 40
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is a continuation of the study ZLB06_001CR with the objective of assessing efficacy, tolerability, safety of IgPro, as well as long-term health-related quality of life in patients with PID.

Condition or Disease	Intervention/Treatment	Phase
Primary Immunodeficiency (PID)	Biological: IgPro20	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Extension Study of the Efficacy, Tolerability, and Safety of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency (IgPro20 EU Extension Study)
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IgPro20 Subcutaneous (SC) administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).	Biological: IgPro20; Other Names: IgG with Proline (IgPro) Hizentra

Outcome Measures

Primary Outcome Measures

1. Total Serum IgG Trough Levels [Up to 42 months]

   The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.

Secondary Outcome Measures

1. Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) [Up to 42 months]

   The annualized rate was based on the total number of SBIs and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included bacterial pneumonia, bacteremia and septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by the Medical Monitor and Investigator to determine if the event fulfilled the predefined criteria for SBIs.

2. Annualized Rate of Infection Episodes [Up to 42 months]

   The annualized rate was based on the total number of infection episodes occurring during the study divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

3. Number of Infection Episodes [Up to 42 months]

   Total number of infections for the specified analysis population

4. Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections [Up to 42 months]

   The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection, and the total number of subject diary days for all subjects in the specified analysis population and adjusted to 365 days.

5. Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections [Up to 42 months]

   Total number of days out of work / school / kindergarten / day care or unable to perform normal activities due to infections, for the specified analysis population

6. Annualized Rate of Hospitalization Due to Infections [Up to 42 months]

   The annualized rate was based on the total number of days of hospitalization due to infections and the total number of subject diary days for all subjects in the specified analysis population and adjusted to 365 days.

7. Number of Days of Hospitalization Due to Infections [Up to 42 months]

   Total number of days of hospitalization due to infections for the specified analysis population

8. Use of Antibiotics for Infection Prophylaxis and Treatment [Up to 42 months]

   Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the specified analysis population, and adjusted to 365 days.

9. Health Related Quality of Life (Short Form 36 Health Survey) [At baseline and at the last available post-baseline observation for each subject (up to 42 months)]

   The Short Form 36 Health Survey (SF-36) is a 36-item questionnaire that measures generic health concepts that are relevant across age, disease, and treatment groups. The questions are grouped into eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores range from 0 to 100, with higher scores indicating a better health state.

10. Clinically Relevant Changes in Vital Signs From Baseline to the Completion Visit. [At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months).]

    The total number of subjects with clinically relevant changes in vital signs from baseline to the completion visit. Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature.

11. Clinically Significant Abnormal Changes in Routine Laboratory Parameters Between Baseline and the Completion Visit. [At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months).]

    The total number of subjects with clinically significant abnormal changes in routine laboratory parameters between baseline and the completion visit. Routine laboratory parameters included haematology, serum chemistry and urinalysis.

12. Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion [Up to 42 months]

    The rate of AEs was the number of AEs over the number of infusions administered. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with primary humoral immunodeficiency, namely with a diagnosis of Common variable immunodeficiency (CVID) as defined by the Pan-American Group for Immunodeficiency (PAGID) and the European Society for Immunodeficiencies (ESID), or X-linked agammaglobulinemia (XLA) as defined by PAGID and ESID, or autosomal recessive agammaglobulinemia who have participated in the study ZLB06_001CR and who have tolerated IgPro well

• Written informed consent

Exclusion Criteria:

• Hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined as total urine protein concentration > 0.2g/L)

• Other significant medical conditions that could increase the risk to the subject

• Females who are pregnant, breast feeding or planning a pregnancy during the course of the study

• Participation in a study with an investigational medicinal product within three months prior to enrollment, except for ZLB06_001CR

• Evidence of uncooperative attitude

• Any condition that is likely to interfere with evaluation of the IMP or satisfactory conduct of the study

• Subjects who are employees at the investigational site, relatives or spouse of the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site	Paris		France	75743
2	Study Site	Berlin		Germany	13353
3	Study Site	Freiburg		Germany	79095
4	Study Site	Leipzig		Germany	04129
5	Study Site	Mainz		Germany	55131
6	Study Site	Warsaw		Poland
7	Study Site	Cluj-Napoca		Romania	400162
8	Study Site	Timisoara		Romania	300011
9	Study Site	Barcelona		Spain	08036
10	Study Site	Sevilla		Spain	41013
11	Study Site	Göteborg		Sweden	41685
12	Study Site	Bern		Switzerland	3010
13	Study Site	London		United Kingdom	EC1A7BE

Sponsors and Collaborators

• CSL Behring

Investigators

• Study Director: Program Director, Clinical R&D, CSL Behring

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT00751621
• Other Study ID Numbers: ZLB07_002CR; 1472; 2008-000830-30
• First Posted: Sep 12, 2008
• Last Update Posted: Apr 2, 2014
• Last Verified: Dec 1, 2012

• Keywords provided by CSL Behring: Immune globulin subcutaneous; SCIG; primary immunodeficiency; PID
• Additional relevant MeSH terms: Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes

Study Results

Participant Flow

Recruitment Details	Subjects who had previously participated in the pivotal study ZLB06_001CR (NCT00542997) were enrolled in the extension study ZLB07_002CR.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous (SC) administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Period Title: Overall Study
STARTED	40
COMPLETED	36
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous (SC) administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Overall Participants	40
Age, Customized (participants) [Number]
2 to < 12 years	15 37.5%
12 to < 16 years	4 10%
16 to < 65 years	21 52.5%
≥ 65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	12 30%
Male	28 70%

Outcome Measures

1. Primary Outcome

Title	Total Serum IgG Trough Levels
Description	The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The "all treated" (AT) safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the "Full Analysis/intention-to-treat" (ITT) data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Mean (Standard Deviation) [g/L]	7.97 (1.171)

2. Secondary Outcome

Title	Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs)
Description	The annualized rate was based on the total number of SBIs and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included bacterial pneumonia, bacteremia and septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by the Medical Monitor and Investigator to determine if the event fulfilled the predefined criteria for SBIs.
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Measure Subject Study Days	38208
Annualized Rate	0.048
Upper 1-sided 99% Confidence Limit	0.1252

3. Secondary Outcome

Title	Annualized Rate of Infection Episodes
Description	The annualized rate was based on the total number of infection episodes occurring during the study divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Measure Subject Study Days	38208
Number (95% Confidence Interval) [infection episodes per subject year]	3.334

4. Secondary Outcome

Title	Number of Infection Episodes
Description	Total number of infections for the specified analysis population
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Number [infection episodes]	349

5. Secondary Outcome

Title	Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections
Description	The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection, and the total number of subject diary days for all subjects in the specified analysis population and adjusted to 365 days.
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Measure Subject Diary Days	38045
Number [days per subject year]	6.773

6. Secondary Outcome

Title	Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections
Description	Total number of days out of work / school / kindergarten / day care or unable to perform normal activities due to infections, for the specified analysis population
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Number [days]	706

7. Secondary Outcome

Title	Annualized Rate of Hospitalization Due to Infections
Description	The annualized rate was based on the total number of days of hospitalization due to infections and the total number of subject diary days for all subjects in the specified analysis population and adjusted to 365 days.
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Measure Subject Diary Days	38045
Number [days per subject year]	1.055

8. Secondary Outcome

Title	Number of Days of Hospitalization Due to Infections
Description	Total number of days of hospitalization due to infections for the specified analysis population
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Number [days]	110

9. Secondary Outcome

Title	Use of Antibiotics for Infection Prophylaxis and Treatment
Description	Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the specified analysis population, and adjusted to 365 days.
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The AT safety data set comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Measure Subject Study Days	38208
Number [days per subject year]	72.13

10. Secondary Outcome

Title	Health Related Quality of Life (Short Form 36 Health Survey)
Description	The Short Form 36 Health Survey (SF-36) is a 36-item questionnaire that measures generic health concepts that are relevant across age, disease, and treatment groups. The questions are grouped into eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores range from 0 to 100, with higher scores indicating a better health state.
Time Frame	At baseline and at the last available post-baseline observation for each subject (up to 42 months)

Outcome Measure Data

Analysis Population Description

The analysis population comprised the Full-Analysis health related quality of life (HRQL) data set (defined as all subjects entered into the study who complete a baseline and at least 1 follow-up HRQL assessment), who were at least 15 years of age.

Arm/Group Title	IgPro20 - At Baseline	IgPro20 - At End of Study
Arm/Group Description	SF-36 score at baseline.	SF-36 score at end of study (defined as the last available post-baseline observation for each subject).
Measure Participants	20	20
Physical Functioning	95.0	100.0
Role-physical	100.0	100.0
Role-emotional	100.0	100.0
Social Functioning	100.0	100.0
Bodily Pain	84.0	84.0
Mental Health	85.0	80.0
Vitality	65.6	75.0
General Health	52.0	54.5

11. Secondary Outcome

Title	Clinically Relevant Changes in Vital Signs From Baseline to the Completion Visit.
Description	The total number of subjects with clinically relevant changes in vital signs from baseline to the completion visit. Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature.
Time Frame	At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months).

Outcome Measure Data

Analysis Population Description

The AT safety data set (which comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available) and for whom vital signs data was collected at both baseline and completion.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	39
Number [participants]	0 0%

12. Secondary Outcome

Title	Clinically Significant Abnormal Changes in Routine Laboratory Parameters Between Baseline and the Completion Visit.
Description	The total number of subjects with clinically significant abnormal changes in routine laboratory parameters between baseline and the completion visit. Routine laboratory parameters included haematology, serum chemistry and urinalysis.
Time Frame	At baseline (data either from Infusion 40 or the completion visit of study ZLB06_001CR), and at completion (up to 42 months).

Outcome Measure Data

Analysis Population Description

The AT safety data set (which comprised all subjects treated with IgPro20 during any study period and was identical to the ITT data set that comprised all subjects treated with IgPro20 and for whom any efficacy data was available) and for whom laboratory parameter data was collected at both baseline and completion.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Haematology	3 7.5%
Serum Chemistry	1 2.5%
Urinalysis	0 0%

13. Secondary Outcome

Title	Rate, Severity and Relatedness of Any Adverse Events (AEs) Per Infusion
Description	The rate of AEs was the number of AEs over the number of infusions administered. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

The AT safety data set comprised all subjects treated with IgPro20 during any study period.

Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
Measure Participants	40
Measure Number of Infusions	5405
Total AEs	0.0936
Mild AEs	0.0685
Moderate AEs	0.0231
Severe AEs	0.0020
At least possibly related AEs	0.0026
Serious AEs	0.0033
At least possibly related and serious AEs	0

Adverse Events

Time Frame	AEs were collected for the duration of the study, up to 42 months.
Adverse Event Reporting Description	A total of 5405 weekly infusions of IgPro20 were administered to 40 subjects in this study. Three subjects received fewer than 100 infusions. The AT safety data set comprised all subjects treated with IgPro20 during any study period. AEs in "General disorders" were collected under the MedDRA SOC General disorders and administration site conditions.
Arm/Group Title	IgPro20
Arm/Group Description	Subcutaneous administration by the subject/parent/guardian with the planned weekly dose of IgPro20 to be the same as the subject's last dose recommended by the investigator in study ZLB06_001CR (NCT00542997).
All Cause Mortality
	IgPro20
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	IgPro20
	Affected / at Risk (%)	# Events
Total	14/40 (35%)
Blood and lymphatic system disorders
Thrombocytopenic purpura	1/40 (2.5%)	1
Agranulocytosis	1/40 (2.5%)	1
Gastrointestinal disorders
Abdominal pain	1/40 (2.5%)	1
Coeliac disease	1/40 (2.5%)	1
Diarrhoea	1/40 (2.5%)	1
General disorders
Face oedema	1/40 (2.5%)	1
Infections and infestations
Pneumonia bacterial	5/40 (12.5%)	5
Pneumonia	1/40 (2.5%)	1
Septic shock	1/40 (2.5%)	1
Injury, poisoning and procedural complications
Concussion	1/40 (2.5%)	1
Spinal column injury	1/40 (2.5%)	1
Fracture	1/40 (2.5%)	1
Lower limb fracture	1/40 (2.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	IgPro20
	Affected / at Risk (%)	# Events
Total	39/40 (97.5%)
Blood and lymphatic system disorders
Anaemia	2/40 (5%)	2
Gastrointestinal disorders
Abdominal pain upper	4/40 (10%)	9
Diarrhoea	3/40 (7.5%)	5
Aphthous stomatitis	3/40 (7.5%)	3
Constipation	2/40 (5%)	2
Gastritis	2/40 (5%)	2
General disorders
Pyrexia	4/40 (10%)	6
Chest pain	2/40 (5%)	2
Infections and infestations
Bronchitis	21/40 (52.5%)	51
Upper respiratory tract infection	18/40 (45%)	49
Sinusitis	13/40 (32.5%)	31
Nasopharyngitis	12/40 (30%)	19
Rhinitis	9/40 (22.5%)	15
Febrile infection	6/40 (15%)	10
Acute sinusitis	5/40 (12.5%)	5
Pharyngitis	5/40 (12.5%)	10
Influenza	4/40 (10%)	4
Viral infection	4/40 (10%)	4
Viral upper respiratory tract infection	4/40 (10%)	5
Conjunctivitis infective	3/40 (7.5%)	11
Ear infection	3/40 (7.5%)	6
Enteritis infectious	3/40 (7.5%)	12
Lower respiratory tract infection	3/40 (7.5%)	6
Oral herpes	3/40 (7.5%)	8
Otitis media	3/40 (7.5%)	8
Pneumonia	2/40 (5%)	2
Urinary tract infection	3/40 (7.5%)	6
Acute tonsillitis	2/40 (5%)	3
Diarrhoea infectious	2/40 (5%)	3
Enterobiasis	2/40 (5%)	3
Gastroenteritis	2/40 (5%)	2
Laryngitis	2/40 (5%)	6
Otitis externa	2/40 (5%)	2
Otitis media acute	2/40 (5%)	2
Injury, poisoning and procedural complications
Contusion	2/40 (5%)	3
Ligament sprain	2/40 (5%)	2
Investigations
Weight increased	3/40 (7.5%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	6/40 (15%)	7
Back pain	3/40 (7.5%)	3
Nervous system disorders
Dizziness	2/40 (5%)	3
Headache	2/40 (5%)	6
Sciatica	2/40 (5%)	2
Respiratory, thoracic and mediastinal disorders
Cough	11/40 (27.5%)	34
Bronchiectasis	3/40 (7.5%)	4
Productive cough	2/40 (5%)	4
Rhinorrhoea	2/40 (5%)	2
Skin and subcutaneous tissue disorders
Skin lesion	2/40 (5%)	2
Urticaria	2/40 (5%)	2
Surgical and medical procedures
Wisdom teeth removal	2/40 (5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.