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A Dose-Finding Study of Subcutaneous Herceptin (Trastuzumab) in Healthy Male Volunteers and Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Females

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00800436
Collaborator
(none)
66
Enrollment
3
Locations
7
Arms
11
Duration (Months)
22
Patients Per Site
2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This two-part study is designed to select the subcutaneous (SC) dose of Herceptin that results in comparable exposure to intravenous (IV) Herceptin in healthy male participants and in HER2-positive female participants. The study will also assess the safety and tolerability of the SC and IV formulations. In Part 1 of the study, four cohorts will be treated with a single dose of Herceptin as follows: Cohort 1 (6 milligrams per kilogram [mg/kg] IV in healthy male participants); Cohort 2 (6 mg/kg IV in HER2-positive female participants); Cohort 3 (6 mg/kg SC in healthy male participants); Cohort 4 (10 mg/kg SC in healthy male participants). An additional cohort of healthy volunteers (Cohort 5) will be opened if both SC dose levels from Cohorts 3 and 4 result in Herceptin exposures different from the target concentration produced by a single IV dose, or if the variability in pharmacokinetic (PK) parameter values cannot be used to define the target SC dose level. In Part 2 of the study, HER2-positive female participants will receive a single dose of SC Herceptin at the dose level defined in Part 1. Participants from Part 1 are eligible to enter Part 2 provided they receive the second (Part 2) study dose of Herceptin a minimum of 22 days after their first (Part 1) dose.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
66 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Two-Part, Multi-Centre, Trastuzumab Dose-Finding Study in Healthy Male Volunteers and HER2 Positive Female Patients
Study Start Date :
Nov 1, 2008
Actual Primary Completion Date :
Oct 1, 2009
Actual Study Completion Date :
Oct 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: Cohort 1

Healthy male participants will receive Herceptin 6 mg/kg IV on Day 1.

Drug: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Other Names:
  • Trastuzumab

    		•
    Experimental: Part 1: Cohort 2

    Female participants with HER2-positive breast cancer will receive Herceptin 6 mg/kg IV on Day 1.

    Drug: Herceptin
    Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
    Other Names:
  • Trastuzumab

    		•
    Experimental: Part 1: Cohort 3

    Healthy male participants will receive Herceptin 6 mg/kg SC on Day 1.

    Drug: Herceptin
    Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
    Other Names:
  • Trastuzumab

    		•
    Experimental: Part 1: Cohort 4

    Healthy male participants will receive Herceptin 10 mg/kg SC on Day 1.

    Drug: Herceptin
    Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
    Other Names:
  • Trastuzumab

    		•
    Experimental: Part 1: Cohort 5

    Healthy male participants will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohorts 1, 2, 3, and 4.

    Drug: Herceptin
    Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
    Other Names:
  • Trastuzumab

    		•
    Experimental: Part 2: Cohort A

    Female participants with HER2-positive breast cancer will receive Herceptin SC at the dose level determined in Part 1.

    Drug: Herceptin
    Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
    Other Names:
  • Trastuzumab

    		•
    Experimental: Part 2: Cohort B

    Female participants with HER2-positive breast cancer will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohort A.

    Drug: Herceptin
    Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
    Other Names:
  • Trastuzumab

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Trastuzumab [Predose (0 hours) and postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)]

      AUCinf represents the area under the concentration-time curve of trastuzumab in serum over the time interval from 0 extrapolated to infinity. Values for AUCinf of trastuzumab were derived by non-compartmental analysis across all pharmacokinetic (PK) collections and expressed in days by micrograms per milliliter (days•μg/mL).

    Secondary Outcome Measures

    1. Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab [Day 22]

      CDay22 of trastuzumab was derived from the single PK collection on Day 22 and expressed in micrograms per milliliter (μg/mL).

    2. Maximum Observed Serum Concentration of Trastuzumab (Cmax) [Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)]

      Cmax of trastuzumab was derived across all post-dose PK collections and expressed in μg/mL.

    3. Time to Maximum Serum Concentration (Tmax) of Trastuzumab [Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)]

      Tmax of trastuzumab was based on the Cmax derived across all post-dose PK collections and expressed in hours.

    4. Terminal Elimination Half-Life (T1/2) of Trastuzumab [Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)]

      T1/2 of trastuzumab was measured as the time required for trastuzumab concentration to decrease by one-half. T1/2 was derived across all PK collections and expressed in hours.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Healthy Participants (Part 1 only)

    • Males 18 to 45 to years of age

    • Baseline left ventricular ejection fraction (LVEF) greater than (>) 60 percent (%)

    • HER2-Positive Females (Parts 1 and 2)

    • Females greater than or equal to (≥) 18 years of age

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0

    • Previous non-metastatic operable primary invasive HER2-positive breast cancer

    • Baseline LVEF >55%

    Exclusion Criteria:

    • Healthy Participants (Part 1 only)

    • Clinically significant abnormalities in laboratory test results or electrocardiogram

    • History of significant allergies, gastrointestinal, renal, hepatic, cardiovascular, or pulmonary disease

    • History of hypersensitivity or allergic reaction, spontaneous or following drug administration

    • History of cardiac conditions

    • HER2-Positive Females (Parts 1 and 2)

    • Metastatic disease

    • Concurrent other malignancy requiring therapy of any modality which may interfere with PK investigations or result in unexpected toxicity

    • Use of Herceptin in previous 5 months

    • Serious cardiac illness

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 East Bentleigh Australia VIC 3165
    2 Christchurch New Zealand 8011
    3 Grafton New Zealand 1150

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT00800436
    Other Study ID Numbers:
    • BP22023
    First Posted:
    Dec 2, 2008
    Last Update Posted:
    Dec 16, 2016
    Last Verified:
    Oct 1, 2016
    Additional relevant MeSH terms:
    Trastuzumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Four participants were counted twice as they were treated in both Cohort 2 and Cohort A.
    Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Arm/Group Description Healthy male participants received Herceptin 6 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1. Female participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received Herceptin 6 mg/kg IV on Day 1. Healthy male participants received Herceptin 6 mg/kg subcutaneously (SC) on Day 1. Healthy male participants received Herceptin 10 mg/kg SC on Day 1. Healthy male participants received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
    Period Title: Overall Study
    STARTED 6 6 6 6 6 20 20
    COMPLETED 6 6 5 5 6 20 20
    NOT COMPLETED 0 0 1 1 0 0 0

    Baseline Characteristics

    Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B Total
    Arm/Group Description Healthy male participants received Herceptin 6 mg/kg IV on Day 1. Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1. Healthy male participants received Herceptin 6 mg/kg SC on Day 1. Healthy male participants received Herceptin 10 mg/kg SC on Day 1. Healthy male participants received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1. Total of all reporting groups
    Overall Participants 6 6 6 6 6 20 20 70
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    22.7
    (2.58)
    46.2
    (5.19)
    25.7
    (9.29)
    23.0
    (6.16)
    22.0
    (4.34)
    50.7
    (7.21)
    51.6
    (9.04)
    41.2
    (14.85)
    Gender (Count of Participants)
    Female
    0
    0%
    6
    100%
    0
    0%
    0
    0%
    0
    0%
    20
    100%
    20
    100%
    46
    65.7%
    Male
    6
    100%
    0
    0%
    6
    100%
    6
    100%
    6
    100%
    0
    0%
    0
    0%
    24
    34.3%

    Outcome Measures

    1. Primary Outcome
    Title Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Trastuzumab
    Description AUCinf represents the area under the concentration-time curve of trastuzumab in serum over the time interval from 0 extrapolated to infinity. Values for AUCinf of trastuzumab were derived by non-compartmental analysis across all pharmacokinetic (PK) collections and expressed in days by micrograms per milliliter (days•μg/mL).
    Time Frame Predose (0 hours) and postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

    Outcome Measure Data

    Analysis Population Description
    PK Population: All enrolled participants who adhered to the protocol (per protocol basis).
    Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Arm/Group Description Healthy male participants received Herceptin 6 mg/kg IV on Day 1. Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1. Healthy male participants received Herceptin 6 mg/kg SC on Day 1. Healthy male participants received Herceptin 10 mg/kg SC on Day 1. Healthy male participants received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
    Measure Participants 6 6 6 6 6 20 20
    Mean (Standard Deviation) [days•μg/mL]
    1610
    (303)
    1800
    (250)
    1350
    (320)
    2500
    (515)
    1960
    (244)
    2090
    (638)
    3550
    (982)
    2. Secondary Outcome
    Title Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab
    Description CDay22 of trastuzumab was derived from the single PK collection on Day 22 and expressed in micrograms per milliliter (μg/mL).
    Time Frame Day 22

    Outcome Measure Data

    Analysis Population Description
    PK Population
    Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Arm/Group Description Healthy male participants received Herceptin 6 mg/kg IV on Day 1. Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1. Healthy male participants received Herceptin 6 mg/kg SC on Day 1. Healthy male participants received Herceptin 10 mg/kg SC on Day 1. Healthy male participants received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
    Measure Participants 6 6 6 6 6 20 20
    Mean (Standard Deviation) [μg/mL]
    25.6
    (12.1)
    27.5
    (7.5)
    31.6
    (12.0)
    51.4
    (15.8)
    39.4
    (5.5)
    37.8
    (10.4)
    60.8
    (22.0)
    3. Secondary Outcome
    Title Maximum Observed Serum Concentration of Trastuzumab (Cmax)
    Description Cmax of trastuzumab was derived across all post-dose PK collections and expressed in μg/mL.
    Time Frame Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

    Outcome Measure Data

    Analysis Population Description
    PK Population
    Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Arm/Group Description Healthy male participants received Herceptin 6 mg/kg IV on Day 1. Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1. Healthy male participants received Herceptin 6 mg/kg SC on Day 1. Healthy male participants received Herceptin 10 mg/kg SC on Day 1. Healthy male participants received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
    Measure Participants 6 6 6 6 6 20 20
    Mean (Standard Deviation) [μg/mL]
    150
    (14.4)
    185
    (42.9)
    66.8
    (11.4)
    102
    (17.2)
    82.0
    (11.3)
    88.4
    (33.3)
    151
    (58.6)
    4. Secondary Outcome
    Title Time to Maximum Serum Concentration (Tmax) of Trastuzumab
    Description Tmax of trastuzumab was based on the Cmax derived across all post-dose PK collections and expressed in hours.
    Time Frame Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

    Outcome Measure Data

    Analysis Population Description
    PK Population
    Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Arm/Group Description Healthy male participants received Herceptin 6 mg/kg IV on Day 1. Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1. Healthy male participants received Herceptin 6 mg/kg SC on Day 1. Healthy male participants received Herceptin 10 mg/kg SC on Day 1. Healthy male participants received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
    Measure Participants 6 6 6 6 6 20 20
    Median (Full Range) [hours]
    1.65
    3.00
    156.00
    132.12
    96.00
    97.13
    96.05
    5. Secondary Outcome
    Title Terminal Elimination Half-Life (T1/2) of Trastuzumab
    Description T1/2 of trastuzumab was measured as the time required for trastuzumab concentration to decrease by one-half. T1/2 was derived across all PK collections and expressed in hours.
    Time Frame Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

    Outcome Measure Data

    Analysis Population Description
    PK Population
    Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Arm/Group Description Healthy male participants received Herceptin 6 mg/kg IV on Day 1. Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1. Healthy male participants received Herceptin 6 mg/kg SC on Day 1. Healthy male participants received Herceptin 10 mg/kg SC on Day 1. Healthy male participants received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
    Measure Participants 6 6 6 6 6 20 20
    Mean (Standard Deviation) [hours]
    254
    (32.2)
    244
    (69.2)
    227
    (55.9)
    240
    (34.4)
    236
    (43.9)
    241
    (48.1)
    270
    (80.1)

    Adverse Events

    Time Frame From Baseline up to 5 months post-dose (up to 5 months overall)
    Adverse Event Reporting Description Analysis Population Description: Safety Population
    Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Arm/Group Description Healthy male participants received Herceptin 6 mg/kg IV on Day 1. Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1. Healthy male participants received Herceptin 6 mg/kg SC on Day 1. Healthy male participants received Herceptin 10 mg/kg SC on Day 1. Healthy male participants received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1. Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
    All Cause Mortality
    Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Other (Not Including Serious) Adverse Events
    Part 1: Cohort 1 Part 1: Cohort 2 Part 1: Cohort 3 Part 1: Cohort 4 Part 1: Cohort 5 Part 2: Cohort A Part 2: Cohort B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/6 (83.3%) 6/6 (100%) 5/6 (83.3%) 5/6 (83.3%) 6/6 (100%) 19/20 (95%) 20/20 (100%)
    Cardiac disorders
    Mitral valve incompetence 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Ear and labyrinth disorders
    Ear pain 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Eye disorders
    Eye irritation 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 1/20 (5%)
    Conjuctival haemorrhage 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Eyelid bleeding 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Scleral hypermia 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/20 (0%) 0/20 (0%)
    Gastrointestinal disorders
    Diarrhoea 2/6 (33.3%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 6/20 (30%) 2/20 (10%)
    Nausea 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 3/20 (15%) 1/20 (5%)
    Abdominal discomfort 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 2/20 (10%)
    Abdominal pain 2/6 (33.3%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Dry mouth 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Abdominal distension 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Aphthous stomatitis 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Dyspepsia 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Faecal incontinence 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Flatulence 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Toothache 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Vomiting 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    General disorders
    Fatigue 1/6 (16.7%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 1/6 (16.7%) 2/20 (10%) 3/20 (15%)
    Injection site erythema 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 4/20 (20%) 2/20 (10%)
    Chest pain 1/6 (16.7%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/20 (10%) 2/20 (10%)
    Injection site discolouration 0/6 (0%) 0/6 (0%) 2/6 (33.3%) 0/6 (0%) 0/6 (0%) 3/20 (15%) 0/20 (0%)
    Influenza like illness 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/6 (16.7%) 1/20 (5%) 0/20 (0%)
    Catheter site haematoma 0/6 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/6 (16.7%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Injection site pain 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/20 (0%) 2/20 (10%)
    Pyrexia 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 2/20 (10%)
    Infusion related reaction 2/6 (33.3%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Injection site swelling 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 2/20 (10%)
    Oedema peripheral 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 1/20 (5%)
    Application site inflammation 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Application site reaction 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Application site vesicles 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Catheter site erythema 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Feeling cold 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Gravitational oedema 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Inflammation 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Injection site discomfort 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Injection site reaction 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Vessel puncture site haematoma 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Catheter site inflammation 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Immune system disorders
    Seasonal allergy 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/20 (0%) 0/20 (0%)
    Infections and infestations
    Upper respiratory tract Infection 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 2/6 (33.3%) 1/6 (16.7%) 4/20 (20%) 5/20 (25%)
    Urinary tract infection 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 2/20 (10%)
    Gastroenteritis 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/20 (10%) 0/20 (0%)
    Influenza 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 1/20 (5%)
    Lower respiratory tract infection 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 2/20 (10%)
    Oral herpes 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Viral infection 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/20 (10%) 0/20 (0%)
    Campylobacter infection 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Dermatitis infected 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Herpes simplex 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Herpes zoster 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Hordeolum 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Nasopharyngitis 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Paronychia 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/20 (0%) 0/20 (0%)
    Respiratory tract infection 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Respiratory tract infection viral 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Sinusitis 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Tooth abscess 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Viral upper respiratory tract infection 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Injury, poisoning and procedural complications
    Contusion 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 1/20 (5%)
    Tooth fracture 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Arthropod bite 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Chest injury 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Excoriation 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Incision site pain 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Joint sprain 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/20 (0%) 0/20 (0%)
    Meniscus lesion 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Skin laceration 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/20 (0%) 0/20 (0%)
    Investigations
    Breath sounds abnormal 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Weight decreased 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Weight increased 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 1/6 (16.7%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 3/20 (15%) 3/20 (15%)
    Myalgia 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 1/6 (16.7%) 1/6 (16.7%) 3/20 (15%) 1/20 (5%)
    Athralgia 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/20 (10%) 1/20 (5%)
    Muscle spasms 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 2/20 (10%)
    Musculoskeletal pain 2/6 (33.3%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Back pain 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 2/20 (10%)
    Bone pain 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/20 (10%) 0/20 (0%)
    Joint crepitation 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Neck pain 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Nervous system disorders
    Headache 3/6 (50%) 2/6 (33.3%) 2/6 (33.3%) 0/6 (0%) 2/6 (33.3%) 12/20 (60%) 14/20 (70%)
    Lethargy 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 4/20 (20%) 2/20 (10%)
    Dizziness 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/20 (10%) 1/20 (5%)
    Restless leg syndrome 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Convulsion 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Hypoaesthesia 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Somnolence 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Tremor 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Psychiatric disorders
    Depressed mood 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 2/20 (10%) 0/20 (0%)
    Initial insomnia 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Panic attack 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Reproductive system and breast disorders
    Breast mass 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Nipple pain 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 1/20 (5%) 1/20 (5%)
    Epistaxis 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 2/20 (10%)
    Oropharyngeal pain 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 2/20 (10%)
    Asthma 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Chronic obstructive pulmonary disease 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Dry throat 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Dysponea 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Nasal congestation 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Pharyngeal stenosis 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Postnasal drip 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Rhinitis allergic 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Rhinorrhoea 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Sneezing 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Skin and subcutaneous tissue disorders
    Acne 0/6 (0%) 2/6 (33.3%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Alopecia 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Erythema 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Rash 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Rash papular 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)
    Skin lesion 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Vascular disorders
    Flushing 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 1/20 (5%)
    Hot flush 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/20 (5%) 0/20 (0%)
    Lymphoedema 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/20 (0%) 0/20 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800-821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT00800436
    Other Study ID Numbers:
    • BP22023
    First Posted:
    Dec 2, 2008
    Last Update Posted:
    Dec 16, 2016
    Last Verified:
    Oct 1, 2016