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Extension of Prior Study Evaluating Safety and Tolerability of Two Doses of Betaseron® to Treat Relapsing-remitting Multiple Sclerosis

Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT00235989
Collaborator
(none)
63
Enrollment
17
Locations
4
Arms
55
Duration (Months)
3.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if a higher dose of study drug is more effective in preventing relapses in patients with Multiple Sclerosis.

Condition or Disease Intervention/Treatment Phase
  • Drug: Interferon beta 1b (Betaseron, BAY86-5046)
  • Drug: Interferon beta 1b (Betaseron, BAY86-5046)
  • Drug: Interferon beta 1b (Betaseron, BAY86-5046)
  • Drug: Interferon beta 1b (Betaseron, BAY86-5046)
 Phase 2

Detailed Description

This study has previously been posted by Berlex, Inc. Berlex, Inc. has been renamed to Bayer HealthCare Pharmaceuticals, Inc.

Bayer HealthCare Pharmaceuticals, Inc.is the sponsor of the trial.

Study Design

Study Type:
Interventional
Actual Enrollment :
63 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Extension Study of the Double-blind, Randomized, Parallel Group, Multicenter Phase 2 Study 307000A to Further Evaluate the Safety and Tolerability of Betaseron® 500 mcg Subcutaneously Every Other Day and Betaseron® 250 mcg Subcutaneously Every Other Day in Patients With Relapsing-remitting Multiple Sclerosis (RRMS)
Study Start Date :
Jun 1, 2003
Actual Primary Completion Date :
Jan 1, 2008
Actual Study Completion Date :
Jan 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: ET: IFNB-1b 250 mcg => 250 mcg

Extension Treatment 250 mcg continued

Drug: Interferon beta 1b (Betaseron, BAY86-5046)
250 mcg administered s.c.(subcutaneous) every other day
Other Names:
  • Betaferon

    		•
    Experimental: ET: IFNB-1b 500 mcg => 250 mcg

    Extension Treatment 500 mcg reduced to 250 mcg

    Drug: Interferon beta 1b (Betaseron, BAY86-5046)
    250 mcg administered s.c. every other day (for patients having received 500 mcg before)
    Other Names:
  • Betaferon

    		•
    Experimental: ET: IFNB-1b 500 mcg => 500 mcg

    Extension Treatment 500 mcg continued

    Drug: Interferon beta 1b (Betaseron, BAY86-5046)
    500 mcg administered s.c. every other day
    Other Names:
  • Betaferon

    		•
    Experimental: ET: IFNB-1b 250 mcg => 500 mcg

    Extension Treatment 250 mcg increased to 500 mcg

    Drug: Interferon beta 1b (Betaseron, BAY86-5046)
    500 mcg administered s.c. every other day (for patients having received 250 mcg before)
    Other Names:
  • Betaferon

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety and Tolerability as Defined by the Number of Subjects With Flu-like Syndrome, Fever, Myalgia, Injection Site Reactions, Injection Site Reactions Pain, Asthenia, Headache, Liver Function Abnormalities, and Bone Marrow Function Abnormalities [At End of Study Visit (week 234)]

      Outcome measures are given as the number of patients with common toxicity by the Common Toxicity Criteria (CTC). Toxicity grading is: Grade 1: no study drug action recommended, Grade 2: Dose reduction or interruption of study treatment should be considered (grade 2 Lymphocyte toxicity required no study drug action), Grade 3: Dose reduction or interruption should be considered; interruption is recommended, and Grade 4: Interruption of study drug is recommended (Grade 4 laboratory toxicity was reported as a serious adverse event). Liver and bone marrow abnormalities are measured by lab tests.

    Secondary Outcome Measures

    1. Frequency (Number of Patients Per Group Defined by Cut Off Values and Per Treatment Arm) of Neutralizing Antibody (NAb) Titer to IFNB-1b [At End of Study Visit (week 234)]

      Serum samples for analysis of NAbs to interferon (IFN) beta-1b were collected in Study 307000A. In the extension study, NAbs were also monitored for information on persistence or resolution. Serum samples of about 6 mL for NAbs were drawn at Weeks 10, 24, 52, 78, 104 130, 156, 182, 208, 234, 260, 286 or the EOS visit. (NU/ml=neutralizing units/ml).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Signed and dated statement of informed consent

    • Completion of Protocol 307000A

    • Negative serum pregnancy test results

    • Agreement to adequate contraception, for female patients

    Exclusion Criteria:

    • Pregnancy or lactation

    • History of alcohol or drug abuse

    • Inability to administer subcutaneous injections either by self or by caregiver

    • Medical, psychiatric or other conditions that compromise the patient's ability to give informed consent, to understand the patient information, to comply with the study protocol, or to complete the study

    • Any significant change in the patient's medical condition after enrollment in Study 307000A which would have lead to his/her exclusion from participation that study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Los Angeles California United States 90095-1721
    2 San Francisco California United States 94117
    3 Washington District of Columbia United States 20037
    4 Atlanta Georgia United States 30309-1465
    5 Chicago Illinois United States 60637
    6 Kansas City Kansas United States 66160
    7 Louisville Kentucky United States 40202
    8 Ann Arbor Michigan United States 48109-0022
    9 Ann Arbor Michigan United States 48109
    10 Reno Nevada United States 89509
    11 Stony Brook New York United States 11794
    12 Durham North Carolina United States 27710
    13 High Point North Carolina United States 27262
    14 Winston-Salem North Carolina United States 27157
    15 Columbus Ohio United States 43221
    16 Nashville Tennessee United States 37212
    17 Nashville Tennessee United States 37232

    Sponsors and Collaborators

    • Bayer

    Investigators

    • Study Director: Bayer Study Director, Bayer

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bayer
    ClinicalTrials.gov Identifier:
    NCT00235989
    Other Study ID Numbers:
    • 91272
    • 307320
    • Beyond
    First Posted:
    Oct 12, 2005
    Last Update Posted:
    May 8, 2014
    Last Verified:
    Apr 1, 2014
    Keywords provided by Bayer
    Relapsing multiple sclerosis
    interferon beta 1b
    Betaferon
    Betaseron
    Additional relevant MeSH terms:
    Multiple Sclerosis
    Multiple Sclerosis, Relapsing-Remitting
    Sclerosis
    Interferons
    Interferon-beta
    Interferon beta-1b

    Study Results

    Participant Flow

    Recruitment Details Eligible patients for this multi-center study included only those who completed in a predecessor study. Patients were enrolled at the end of the preceding study, from 03 Jun 2003 until 06 Jun 2003. Patients who interrupted study medication in accordance with the investigator were eligible, provided it did not result in premature End of Study (EOS).
    Pre-assignment Detail For the first 10 weeks of this extension study, patients remained on the IFNB-1b dosage assigned in Study 307000A (Core Treatment). At the Week 10 visit, patients were unblinded by the sponsor and given a choice of drug dosage. They could continue on the original doses, 250 or 500 micrograms, or could change to the other dose (Extension Treatment).
    Arm/Group Title ET: IFNB-1b 250 mcg => 250 mcg ET: IFNB-1b 500 mcg => 250 mcg ET: IFNB-1b 500 mcg => 500 mcg ET: IFNB-1b 250 mcg => 500 mcg CT: IFNB-1b 250mcg CT: IFNB-1b 500mcg
    Arm/Group Description Extension Treatment 250 mcg continued Extension Treatment 500 mcg reduced to 250 mcg Extension Treatment 500 mcg continued Extension Treatment 250 mcg increased to 500 mcg Core Treatment 250 mcg Core Treatment 500 mcg
    Period Title: Core Treatment Period (CT)
    STARTED 0 0 0 0 36 27
    COMPLETED 0 0 0 0 36 25
    NOT COMPLETED 0 0 0 0 0 2
    Period Title: Core Treatment Period (CT)
    STARTED 16 6 19 20 0 0
    COMPLETED 8 2 14 14 0 0
    NOT COMPLETED 8 4 5 6 0 0

    Baseline Characteristics

    Arm/Group Title ET: IFNB-1b 250 mcg => 250 mcg ET: IFNB-1b 500 mcg => 250 mcg ET: IFNB-1b 500 mcg => 500 mcg ET: IFNB-1b 250 mcg => 500 mcg Total
    Arm/Group Description Extension Treatment 250 mcg continued Extension Treatment 500 mcg reduced to 250 mcg Extension Treatment 500 mcg continued Extension Treatment 250 mcg increased to 500 mcg Total of all reporting groups
    Overall Participants 16 6 19 20 61
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    37.8
    (9.22)
    32.2
    (6.79)
    38.8
    (7.57)
    39.3
    (7.17)
    38.1
    (7.98)
    Age, Customized (participants) [Number]
    >20-30 years
    3
    18.8%
    2
    33.3%
    3
    15.8%
    1
    5%
    9
    14.8%
    >30-40 years
    7
    43.8%
    3
    50%
    6
    31.6%
    10
    50%
    26
    42.6%
    >40-50 years
    4
    25%
    1
    16.7%
    8
    42.1%
    8
    40%
    21
    34.4%
    >50 years
    2
    12.5%
    0
    0%
    2
    10.5%
    1
    5%
    5
    8.2%
    Sex: Female, Male (Count of Participants)
    Female
    14
    87.5%
    3
    50%
    15
    78.9%
    12
    60%
    44
    72.1%
    Male
    2
    12.5%
    3
    50%
    4
    21.1%
    8
    40%
    17
    27.9%

    Outcome Measures

    1. Primary Outcome
    Title Safety and Tolerability as Defined by the Number of Subjects With Flu-like Syndrome, Fever, Myalgia, Injection Site Reactions, Injection Site Reactions Pain, Asthenia, Headache, Liver Function Abnormalities, and Bone Marrow Function Abnormalities
    Description Outcome measures are given as the number of patients with common toxicity by the Common Toxicity Criteria (CTC). Toxicity grading is: Grade 1: no study drug action recommended, Grade 2: Dose reduction or interruption of study treatment should be considered (grade 2 Lymphocyte toxicity required no study drug action), Grade 3: Dose reduction or interruption should be considered; interruption is recommended, and Grade 4: Interruption of study drug is recommended (Grade 4 laboratory toxicity was reported as a serious adverse event). Liver and bone marrow abnormalities are measured by lab tests.
    Time Frame At End of Study Visit (week 234)

    Outcome Measure Data

    Analysis Population Description
    The statistical analysis was descriptive. For Liver Function Toxicity grading, the total number of patients for 250 micrograms (mcg) - 500 mcg group was 19 instead of 20 for all analyses.
    Arm/Group Title ET: IFNB-1b 250 mcg => 250 mcg ET: IFNB-1b 500 mcg => 250 mcg ET: IFNB-1b 500 mcg => 500 mcg ET: IFNB-1b 250 mcg => 500 mcg
    Arm/Group Description Extension Treatment 250 mcg continued Extension Treatment 500 mcg reduced to 250 mcg Extension Treatment 500 mcg continued Extension Treatment 250 mcg increased to 500 mcg
    Measure Participants 16 6 19 20
    Incidence of flu-like syndrome
    1
    6.3%
    1
    16.7%
    4
    21.1%
    7
    35%
    Incidence of fever
    1
    6.3%
    0
    0%
    1
    5.3%
    0
    0%
    Incidence of myalgia
    0
    0%
    0
    0%
    1
    5.3%
    0
    0%
    Incidence of injection site reactions
    2
    12.5%
    3
    50%
    4
    21.1%
    3
    15%
    Incidence of injection site reactions pain
    0
    0%
    0
    0%
    1
    5.3%
    0
    0%
    Incidence of asthenia
    4
    25%
    1
    16.7%
    2
    10.5%
    3
    15%
    Incidence of headache
    2
    12.5%
    0
    0%
    2
    10.5%
    3
    15%
    Incidence of grade 1 toxicity (ALAT)
    4
    25%
    1
    16.7%
    8
    42.1%
    9
    45%
    Incidence of grade 2 toxicity (ALAT)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 3 toxicity (ALAT)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 4 toxicity (ALAT)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 1 toxicity (ASAT)
    2
    12.5%
    1
    16.7%
    8
    42.1%
    7
    35%
    Incidence of grade 2 toxicity (ASAT)
    1
    6.3%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 3 toxicity (ASAT)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 4 toxicity (ASAT)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 1 toxicity (Bilirubin total)
    10
    62.5%
    4
    66.7%
    10
    52.6%
    14
    70%
    Incidence of grade 2 toxicity (Bilirubin total)
    0
    0%
    0
    0%
    1
    5.3%
    0
    0%
    Incidence of grade 3 toxicity (Bilirubin total)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 4 toxicity (Bilirubin total)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 1 toxicity (Leukocytes)
    3
    18.8%
    3
    50%
    4
    21.1%
    6
    30%
    Incidence of grade 2 toxicity (Leukocytes)
    1
    6.3%
    0
    0%
    1
    5.3%
    2
    10%
    Incidence of grade 3 toxicity (Leukocytes)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 4 toxicity (Leukocytes)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 1 toxicity (Lymphocytes)
    0
    0%
    0
    0%
    1
    5.3%
    5
    25%
    Incidence of grade 2 toxicity (Lymphocytes)
    2
    12.5%
    0
    0%
    1
    5.3%
    1
    5%
    Incidence of grade 3 toxicity (Lymphocytes)
    0
    0%
    0
    0%
    0
    0%
    1
    5%
    Incidence of grade 4 toxicity (Lymphocytes)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 1 toxicity (Platelets)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 2 toxicity (Platelets)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 3 toxicity (Platelets)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 4 toxicity (Platelets)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 1 toxicity (Hemoglobin)
    0
    0%
    0
    0%
    1
    5.3%
    1
    5%
    Incidence of grade 2 toxicity (Hemoglobin)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Incidence of grade 3 toxicity (Hemoglobin)
    0
    0%
    0
    0%
    1
    5.3%
    0
    0%
    Incidence of grade 4 toxicity (Hemoglobin)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Secondary Outcome
    Title Frequency (Number of Patients Per Group Defined by Cut Off Values and Per Treatment Arm) of Neutralizing Antibody (NAb) Titer to IFNB-1b
    Description Serum samples for analysis of NAbs to interferon (IFN) beta-1b were collected in Study 307000A. In the extension study, NAbs were also monitored for information on persistence or resolution. Serum samples of about 6 mL for NAbs were drawn at Weeks 10, 24, 52, 78, 104 130, 156, 182, 208, 234, 260, 286 or the EOS visit. (NU/ml=neutralizing units/ml).
    Time Frame At End of Study Visit (week 234)

    Outcome Measure Data

    Analysis Population Description
    For the NAb analyses data were provided for 40 patients instead of 61 for week 234. Twenty-one patients had no data at this visit.The entries in the table are the number of patients with positive titer in the extension treatment cohorts for the three cutoff titer values. The analyses provide frequencies of positive titers.
    Arm/Group Title ET: IFNB-1b 250 mcg => 250 mcg ET: IFNB-1b 500 mcg => 250 mcg ET: IFNB-1b 500 mcg => 500 mcg ET: IFNB-1b 250 mcg => 500 mcg
    Arm/Group Description Extension Treatment 250 mcg continued Extension Treatment 500 mcg reduced to 250 mcg Extension Treatment 500 mcg continued Extension Treatment 250 mcg increased to 500 mcg
    Measure Participants 8 2 15 15
    NAbs titer, cut-off value 20 NU/ml (minimum)
    2
    12.5%
    0
    0%
    5
    26.3%
    3
    15%
    NAbs titer, cut-off value 100 NU/ml (minimum)
    1
    6.3%
    0
    0%
    2
    10.5%
    2
    10%
    NAbs titer, cut-off value 400 NU/ml (minimum)
    1
    6.3%
    0
    0%
    1
    5.3%
    1
    5%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title ET: IFNB-1b 250 mcg => 250 mcg ET: IFNB-1b 500 mcg => 250 mcg ET: IFNB-1b 500 mcg => 500 mcg ET: IFNB-1b 250 mcg => 500 mcg
    Arm/Group Description Extension Treatment 250 mcg continued Extension Treatment 500 mcg reduced to 250 mcg Extension Treatment 500 mcg continued Extension Treatment 250 mcg increased to 500 mcg
    All Cause Mortality
    ET: IFNB-1b 250 mcg => 250 mcg ET: IFNB-1b 500 mcg => 250 mcg ET: IFNB-1b 500 mcg => 500 mcg ET: IFNB-1b 250 mcg => 500 mcg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    ET: IFNB-1b 250 mcg => 250 mcg ET: IFNB-1b 500 mcg => 250 mcg ET: IFNB-1b 500 mcg => 500 mcg ET: IFNB-1b 250 mcg => 500 mcg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/16 (12.5%) 0/6 (0%) 9/19 (47.4%) 4/20 (20%)
    Blood and lymphatic system disorders
    Lymphadenopathy 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Cardiac disorders
    Myocardial Infarct 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Pericarditis 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Supraventricular Tachycardia 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Gastrointestinal disorders
    Abdominal Pain 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Esophagitis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Gastrointestinal Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Nausea 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Rectal Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Vomiting 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    General disorders
    Chills 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Fever 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Necrosis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Hepatobiliary disorders
    Cholelithiasis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Infections and infestations
    Sepsis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Bronchitis 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Pneumonia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Otitis Media 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Pyelonephritis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Musculoskeletal and connective tissue disorders
    Joint Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Nervous system disorders
    Cerebral Ischemia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Cerebrovascular Accident 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Grand Mal Convulsion 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Headache 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Multiple Sclerosis 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Renal and urinary disorders
    Kidney Calculus 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Reproductive system and breast disorders
    Breast Enlargement 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Endometrial Disorder 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Embolus 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Dyspnea 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Lung Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Lung Edema 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Pleural Effusion 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Surgical and medical procedures
    Surgery 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Vascular disorders
    Occlusion 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Peripheral Vascular Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Other (Not Including Serious) Adverse Events
    ET: IFNB-1b 250 mcg => 250 mcg ET: IFNB-1b 500 mcg => 250 mcg ET: IFNB-1b 500 mcg => 500 mcg ET: IFNB-1b 250 mcg => 500 mcg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/16 (93.8%) 6/6 (100%) 19/19 (100%) 20/20 (100%)
    Blood and lymphatic system disorders
    Anemia 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 1/20 (5%)
    Leukopenia 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 3/20 (15%)
    Normocytic Anemia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Lymphadenopathy 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Cardiac disorders
    Cardiomegaly 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Cardiovascular Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Pericarditis 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Ear and labyrinth disorders
    Vertigo 2/16 (12.5%) 0/6 (0%) 0/19 (0%) 2/20 (10%)
    Deafness 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Ear Disorder 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Ear Pain 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Endocrine disorders
    Adrenal Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Goiter 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Hypothyreodism 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 1/20 (5%)
    Eye disorders
    Ophthalmoplegia 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Blurred Vision 2/16 (12.5%) 0/6 (0%) 2/19 (10.5%) 5/20 (25%)
    Diplopia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Eye Disorder 0/16 (0%) 1/6 (16.7%) 0/19 (0%) 0/20 (0%)
    Eye Pain 0/16 (0%) 0/6 (0%) 3/19 (15.8%) 1/20 (5%)
    Ptosis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Pupillary Disorder 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Refraction Disorder 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Retinal Disorder 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Gastrointestinal disorders
    Abdominal Pain 1/16 (6.3%) 1/6 (16.7%) 3/19 (15.8%) 1/20 (5%)
    Constipation 1/16 (6.3%) 1/6 (16.7%) 1/19 (5.3%) 2/20 (10%)
    Diarrhea 1/16 (6.3%) 0/6 (0%) 3/19 (15.8%) 0/20 (0%)
    Duodenitis 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Dyspepsia 3/16 (18.8%) 0/6 (0%) 1/19 (5.3%) 4/20 (20%)
    Dysphagia 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Esophageal Ulcer 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Fecal Incontinence 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Gastritis 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Ginigivitis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Gum Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Hemorrhoids 0/16 (0%) 1/6 (16.7%) 0/19 (0%) 0/20 (0%)
    Increased Salivation 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Nausea 3/16 (18.8%) 0/6 (0%) 4/19 (21.1%) 3/20 (15%)
    Rectal Bleeding 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Rectal Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Tongue Pain 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Tooth Caries 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Tooth Disorder 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Vomiting 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Dry Mouth 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    General disorders
    Ashthenia 4/16 (25%) 1/6 (16.7%) 2/19 (10.5%) 3/20 (15%)
    Chills 0/16 (0%) 0/6 (0%) 3/19 (15.8%) 0/20 (0%)
    Cyst 1/16 (6.3%) 0/6 (0%) 3/19 (15.8%) 1/20 (5%)
    Face Edema 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Fever 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Hernia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Malaise 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Pain 2/16 (12.5%) 2/6 (33.3%) 4/19 (21.1%) 5/20 (25%)
    Chest Pain 1/16 (6.3%) 0/6 (0%) 2/19 (10.5%) 0/20 (0%)
    Injection Site Necrosis 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Injection Site Pain 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Injection Site Reaction 2/16 (12.5%) 3/6 (50%) 4/19 (21.1%) 3/20 (15%)
    Edema 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Peripheral Edema 1/16 (6.3%) 0/6 (0%) 2/19 (10.5%) 0/20 (0%)
    Abnormal Gait 0/16 (0%) 0/6 (0%) 0/19 (0%) 2/20 (10%)
    Immune system disorders
    Allergic Reaction 1/16 (6.3%) 0/6 (0%) 3/19 (15.8%) 2/20 (10%)
    Infections and infestations
    Abscess 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Flu Syndrom 1/16 (6.3%) 1/6 (16.7%) 4/19 (21.1%) 7/20 (35%)
    Infection 2/16 (12.5%) 0/6 (0%) 2/19 (10.5%) 3/20 (15%)
    Gastroenteritis 0/16 (0%) 0/6 (0%) 3/19 (15.8%) 1/20 (5%)
    Peridontal Abscess 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Injection Site Abscess 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Bronchitis 4/16 (25%) 1/6 (16.7%) 3/19 (15.8%) 2/20 (10%)
    Pharyngitis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Pneumonia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 3/20 (15%)
    Rhinitis 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Sinusitis 2/16 (12.5%) 1/6 (16.7%) 5/19 (26.3%) 5/20 (25%)
    Upper Respiratory Infection 5/16 (31.3%) 1/6 (16.7%) 2/19 (10.5%) 7/20 (35%)
    Fungal Dermatitis 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 0/20 (0%)
    Otitis Media 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Cystitis 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Urethritis 0/16 (0%) 1/6 (16.7%) 0/19 (0%) 0/20 (0%)
    Urinary Tract Infection 4/16 (25%) 0/6 (0%) 6/19 (31.6%) 3/20 (15%)
    Vaginitis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Injury, poisoning and procedural complications
    Accidental Injury 1/16 (6.3%) 0/6 (0%) 4/19 (21.1%) 3/20 (15%)
    Bone Fracture (not spontaneous) 2/16 (12.5%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Investigations
    Hormone Level altered 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 0/20 (0%)
    Laboratory Test abnormal 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 0/20 (0%)
    Decreased Hemoglobin 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 0/20 (0%)
    Platelet Count decreased 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Gamma-GT increased 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 3/20 (15%)
    SGOT increased 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    SGPT increased 0/16 (0%) 0/6 (0%) 0/19 (0%) 2/20 (10%)
    Weight Gain 2/16 (12.5%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Weight Loss 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Papanicolaou Smear suspicious 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Metabolism and nutrition disorders
    Anorexia 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Diabetes Mellitus 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Avitaminosis 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Hypercalcemia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Hypercholesterolemia 1/16 (6.3%) 0/6 (0%) 3/19 (15.8%) 1/20 (5%)
    Hyperlipemia 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Hypoglycemia 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Hypokalemia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Musculoskeletal and connective tissue disorders
    Back Pain 2/16 (12.5%) 0/6 (0%) 1/19 (5.3%) 2/20 (10%)
    Heaviness in Extremities 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 0/20 (0%)
    Neck Pain 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Pain in Extremity 3/16 (18.8%) 0/6 (0%) 5/19 (26.3%) 3/20 (15%)
    Arthralgia 0/16 (0%) 0/6 (0%) 0/19 (0%) 3/20 (15%)
    Arthritis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Bone Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 2/20 (10%)
    Bone Pain 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Bursitis 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Joint Disorder 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Muscle Cramps 3/16 (18.8%) 0/6 (0%) 2/19 (10.5%) 2/20 (10%)
    Myalgia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Myasthenia 3/16 (18.8%) 2/6 (33.3%) 3/19 (15.8%) 7/20 (35%)
    Tendon Disorder 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Tenosynovitis 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Twitching 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Breast Neoplasm 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 0/20 (0%)
    Skin Benign Neoplasm 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Adenoma 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Nervous system disorders
    Cerebral Infarct 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Migraine 1/16 (6.3%) 0/6 (0%) 4/19 (21.1%) 0/20 (0%)
    Syncope 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Amnesia 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Ataxia 4/16 (25%) 0/6 (0%) 1/19 (5.3%) 2/20 (10%)
    Dizziness 0/16 (0%) 0/6 (0%) 3/19 (15.8%) 2/20 (10%)
    Dysarthria 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Foot Drop 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Headache 2/16 (12.5%) 0/6 (0%) 2/19 (10.5%) 3/20 (15%)
    Hypalgesia 1/16 (6.3%) 0/6 (0%) 3/19 (15.8%) 0/20 (0%)
    Hyperkinesia 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Hypertonia 3/16 (18.8%) 0/6 (0%) 3/19 (15.8%) 1/20 (5%)
    Hypesthesia 5/16 (31.3%) 3/6 (50%) 7/19 (36.8%) 9/20 (45%)
    Incoordination 2/16 (12.5%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Multiple Sclerosis 4/16 (25%) 3/6 (50%) 2/19 (10.5%) 6/20 (30%)
    Neuralgia 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 2/20 (10%)
    Neuropathy 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Nystagmus 2/16 (12.5%) 0/6 (0%) 1/19 (5.3%) 3/20 (15%)
    Paresthesia 5/16 (31.3%) 3/6 (50%) 7/19 (36.8%) 5/20 (25%)
    Reflexes decreased 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Reflexes increased 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Somnolence 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Speech Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Tremor 1/16 (6.3%) 1/6 (16.7%) 0/19 (0%) 1/20 (5%)
    Optic Neuritis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Taste Perversion 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Visual Field Defect 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Psychiatric disorders
    Anxiety 2/16 (12.5%) 1/6 (16.7%) 2/19 (10.5%) 2/20 (10%)
    Confusion 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Depression 4/16 (25%) 3/6 (50%) 4/19 (21.1%) 0/20 (0%)
    Emotional Lability 0/16 (0%) 1/6 (16.7%) 0/19 (0%) 0/20 (0%)
    Insomnia 2/16 (12.5%) 1/6 (16.7%) 3/19 (15.8%) 4/20 (20%)
    Libido decreased 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Nervousness 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Thinking abnormal 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Renal and urinary disorders
    Uremia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Increased Urinary Frequency 1/16 (6.3%) 1/6 (16.7%) 0/19 (0%) 0/20 (0%)
    Kidney Calculus 0/16 (0%) 0/6 (0%) 2/19 (10.5%) 0/20 (0%)
    Urinary Incontinence 0/16 (0%) 0/6 (0%) 0/19 (0%) 2/20 (10%)
    Urinary Retention 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Urinary Tract Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Urinary Urgency 1/16 (6.3%) 1/6 (16.7%) 0/19 (0%) 1/20 (5%)
    Urination impaired 0/16 (0%) 1/6 (16.7%) 1/19 (5.3%) 1/20 (5%)
    Reproductive system and breast disorders
    Pelvic Pain 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Female Lactation 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Dysmenorrhea 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Dyspareunia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Genital Leukoplakia 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Impotence 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Leukorrhea 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Menstrual Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Metrorrhagia 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Vulvovaginal Disorder 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Respiratory, thoracic and mediastinal disorders
    Sore Throat 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 2/20 (10%)
    Apnea 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Atelectasis 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Cough increased 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Dyspnea 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Lung Disorder 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Nasal Septum Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Pleural Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Pleural Effusion 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Respiratory Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Skin and subcutaneous tissue disorders
    Ecchymosis 0/16 (0%) 0/6 (0%) 0/19 (0%) 2/20 (10%)
    Sweating increased 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Acne 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Alopecia 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Petechial Rash 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Pruritus 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Psoriasis 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)
    Rash 1/16 (6.3%) 0/6 (0%) 1/19 (5.3%) 1/20 (5%)
    Skin Discoloration 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Skin Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 3/20 (15%)
    Skin Necrosis 0/16 (0%) 0/6 (0%) 0/19 (0%) 1/20 (5%)
    Skin Ulcer 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Urticaria 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Surgical and medical procedures
    Surgery 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 2/20 (10%)
    Vascular disorders
    Hypertension 2/16 (12.5%) 0/6 (0%) 2/19 (10.5%) 3/20 (15%)
    Peripheral Vascular Disorder 0/16 (0%) 1/6 (16.7%) 0/19 (0%) 0/20 (0%)
    Vascular Disorder 0/16 (0%) 0/6 (0%) 1/19 (5.3%) 0/20 (0%)
    Hot Flashes 1/16 (6.3%) 0/6 (0%) 0/19 (0%) 0/20 (0%)

    Limitations/Caveats

    The 40 patients in the NAb frequency summaries are the total number of patients with NAb titers at week 234. Official HARTS-to-MedDRA Mapping was used.

    More Information

    Certain Agreements

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

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Therapeutic Area Head
    Organization BAYER
    Phone
    Email clinical-trials-contact@bayerhealthcare.com
    Responsible Party:
    Bayer
    ClinicalTrials.gov Identifier:
    NCT00235989
    Other Study ID Numbers:
    • 91272
    • 307320
    • Beyond
    First Posted:
    Oct 12, 2005
    Last Update Posted:
    May 8, 2014
    Last Verified:
    Apr 1, 2014