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Open Label Extension Study of Conatumumab and Ganitumab (AMG 479)

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT01327612
Collaborator
(none)
12
Enrollment
12
Locations
4
Arms
107.1
Actual Duration (Months)
1
Patient Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this protocol is to allow continued treatment with conatumumab and/or ganitumab, with or without chemotherapy, to participants who completed a separate Amgen-sponsored conatumumab or ganitumab study without disease progression whose previous studies were closed.

Condition or Disease Intervention/Treatment Phase
  • Drug: Modified FOLFOX6
  • Biological: Conatumumab
  • Biological: Ganitumab
  • Biological: Bevacizumab
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Open Label Extension Study of Conatumumab and AMG 479
Actual Study Start Date :
Mar 3, 2011
Actual Primary Completion Date :
Feb 5, 2020
Actual Study Completion Date :
Feb 5, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Conatumumab Monotherapy

Participants will continue to receive conatumumab every 2 weeks (Q2W) or every 3 weeks (Q3W) at the same dose and regimen as at the conclusion of the parent study.

Biological: Conatumumab
Administered by intravenous infusion Q2W or Q3W.
Other Names:
  • AMG 655

    		•
    Experimental: Conatumumab + Ganitumab

    Participants will receive conatumumab and ganitumab by intravenous infusion at the same dose and regimen as at the conclusion of the parent study.

    Biological: Conatumumab
    Administered by intravenous infusion Q2W or Q3W.
    Other Names:
  • AMG 655

    • Biological: Ganitumab
    Administered by intravenous infusion Q3W or Q4W.
    Other Names:
  • AMG 479

    		•
    Experimental: Ganitumab Monotherapy

    Participants will continue to receive ganitumab Q3W or every 4 weeks (Q4W) at the same dose and regimen as at the conclusion of the parent study.

    Biological: Ganitumab
    Administered by intravenous infusion Q3W or Q4W.
    Other Names:
  • AMG 479

    		•
    Experimental: Conatumumab + mFOLFOX6 ± Bevacizumab

    Participants will continue to receive conatumumab by intravenous infusion in addition to modified FOLFOX6 chemotherapy with or without bevacizumab.

    Drug: Modified FOLFOX6
    The mFOLFOX6 regimen is a combination therapy of oxaliplatin 85 mg/m² administered as a 2-hour intravenous (IV) infusion on day 1 and leucovorin 400 mg/m² racemate or 200 mg/m² levo-leucovorin administered as a 2-hour infusion on day 1, followed by a loading dose of 5-fluorouracil (5-FU) 400 mg/m² IV bolus administered on day 1, then 5-FU 2400 mg/m² via ambulatory pump administered for a period of 46 to 48 hours every 14 days.
    Other Names:
  • Oxaliplatin-Leucovorin-Fluorouracil chemotherapy

    • Biological: Conatumumab
    Administered by intravenous infusion Q2W or Q3W.
    Other Names:
  • AMG 655

    • Biological: Bevacizumab
    Administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle.
    Other Names:
  • Avastin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events [From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.]

      An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment.

    2. Number of Participants With Serious Adverse Events [From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.]

      A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: fatal, life threatening (places the participant at immediate risk of death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, and/or other medically important serious event.

    Secondary Outcome Measures

    1. Maximum Change From Baseline in Blood Pressure [Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.]

      Maximum change from baseline is defined for each participant as the maximum change from baseline value observed across all visits.

    2. Minimum Change From Baseline in Blood Pressure [Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.]

      Minimum change from baseline is defined for each participant as the minimum change from baseline value observed across all visits.

    3. Number of Participants With CTCAE Grade 3 or Higher Clinical Laboratory Toxicities [From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.]

      Laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

    4. Best Overall Response [Approximately every 6 months until end of treatment; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.]

      Radiological assessments to evaluate disease extent (with change compared to nadir from the parent protocol) were performed at regular intervals, at a minimum once every 6 months or more frequently if clinically indicated (starting from their last scan on the parent protocol), per standard of care (SOC) at each facility. Tumor response was assessed by the Investigator as either complete response, partial response, stable disease, or progressive disease.

    5. Number of Participants With Disease Progression or Death Due to Disease Progression [From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • To be enrolled in this study, subjects must be currently enrolled in a prior Amgen-sponsored conatumumab or AMG 479 study and are eligible according to the parent study to receive their next dose of conatumumab (with or without co-therapy), or AMG 479 alone.

    Subjects must have their eligibility assessed for this study and be enrolled within 30 days of their last treatment on the parent protocol

    Exclusion Criteria:

    • Discontinued from a conatumumab study due to an adverse event considered by the investigator to be related to conatumumab treatment, including intolerance to conatumumab

    • Subjects determined to have disease progression during their participation in the parent Amgen study

    • Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions ie, double barrier contraceptive methods (eg, diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last dose of protocol-specified therapy administration

    • Subject is pregnant or breast feeding, or planning to become pregnant within 6 months after the last dose of protocol-specified therapy administration

    • Male subject with a pregnant partner who is not willing to use a condom during treatment and for an additional 6 months after the last dose of protocol-specified therapy administration

    • Subject has previously entered this study

    • Subject will not be available for protocol required study visits, to the best of the subject and investigator's knowledge

    • Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Duarte California United States 91010
    2 Research Site La Jolla California United States 92093-0957
    3 Research Site Denver Colorado United States 80218
    4 Research Site Tampa Florida United States 33612
    5 Research Site Ann Arbor Michigan United States 48109
    6 Research Site Buffalo New York United States 14263
    7 Research Site Memphis Tennessee United States 38120
    8 Research Site Houston Texas United States 77030
    9 Research Site San Antonio Texas United States 78229
    10 Research Site Ogden Utah United States 84403
    11 Research Site Szczecin Poland 70-891
    12 Research Site Barcelona Cataluña Spain 08035

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01327612
    Other Study ID Numbers:
    • 20101116
    • 2010-022270-14
    First Posted:
    Apr 1, 2011
    Last Update Posted:
    Feb 21, 2021
    Last Verified:
    Feb 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Amgen
    AMG 655
    AMG 479
    Apoptosis
    Monoclonal Antibody
    Tumor Necrosis Factor
    Insulin-like Growth Factor
    Bevacizumab
    Modified FOLFOX6
    mFOLFOX6
    FOLFOX
    Lymphoma
    Trail Receptor
    ganitumab
    conatumumab
    Additional relevant MeSH terms:
    Neoplasms
    Neoplasm Metastasis
    Carcinoid Tumor
    Leucovorin
    Bevacizumab
    Conatumumab
    Fluorouracil
    Oxaliplatin

    Study Results

    Participant Flow

    Recruitment Details This study enrolled participants with different types of solid tumors who had completed one of the following Amgen-sponsored conatumumab or ganitumab studies: 20050118 (NCT00562380) 20050171 20060295 (NCT00534027) 20060340 (NCT00791011) 20060464 (NCT00625651) 20070411 (NCT00819169). Participants who had not progressed in the parent study were eligible to participate in this trial. The study was conducted at 12 centers in the United States, Spain, and Poland.
    Pre-assignment Detail This was an extension study that permitted participants to continue treatment with conatumumab, with or without co-therapy (modified FOLFOX6 chemotherapy with or without bevacizumab, or ganitumab), or with ganitumab alone, administered at the same dose level and schedule that participants received at the conclusion of the parent study. Participants remained on treatment until disease progression, intolerability, or withdrawal of consent. Results are reported by parent study and treatment.
    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 (mFOLFOX6) chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg + ganitumab 18 mg/kg once every 3 weeks by intravenous infusion.
    Period Title: Overall Study
    STARTED 2 1 1 1 2 3 2
    COMPLETED 1 0 0 0 0 0 0
    NOT COMPLETED 1 1 1 1 2 3 2

    Baseline Characteristics

    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg Total
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg + ganitumab 18 mg/kg once every 3 weeks by intravenous infusion. Total of all reporting groups
    Overall Participants 2 1 1 1 2 3 2 12
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60.0
    (14.1)
    57.0
    44.0
    46.0
    66.5
    (7.8)
    56.3
    (8.7)
    68.0
    (15.6)
    58.8
    (11.1)
    Age, Customized (Count of Participants)
    18 - 64 years
    1
    50%
    1
    100%
    1
    100%
    1
    100%
    1
    50%
    2
    66.7%
    1
    50%
    8
    66.7%
    65 - 74 years
    1
    50%
    0
    0%
    0
    0%
    0
    0%
    1
    50%
    1
    33.3%
    0
    0%
    3
    25%
    75 - 84 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    50%
    1
    8.3%
    ≥ 85 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    1
    50%
    0
    0%
    1
    100%
    0
    0%
    1
    50%
    1
    33.3%
    1
    50%
    5
    41.7%
    Male
    1
    50%
    1
    100%
    0
    0%
    1
    100%
    1
    50%
    2
    66.7%
    1
    50%
    7
    58.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    2
    100%
    1
    100%
    1
    100%
    1
    100%
    2
    100%
    3
    100%
    2
    100%
    12
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    8.3%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    8.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    2
    100%
    1
    100%
    1
    100%
    1
    100%
    2
    100%
    1
    33.3%
    2
    100%
    10
    83.3%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Adverse Events
    Description An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment.
    Time Frame From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of conatumumab or ganitumab.
    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg + ganitumab 18 mg/kg once every 3 weeks by intravenous infusion.
    Measure Participants 2 1 1 1 2 3 2
    Count of Participants [Participants]
    2
    100%
    1
    100%
    1
    100%
    1
    100%
    2
    100%
    3
    100%
    2
    100%
    2. Primary Outcome
    Title Number of Participants With Serious Adverse Events
    Description A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: fatal, life threatening (places the participant at immediate risk of death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, and/or other medically important serious event.
    Time Frame From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of conatumumab or ganitumab.
    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg and ganitumab 18 mg/kg once every 3 weeks by intravenous infusion.
    Measure Participants 2 1 1 1 2 3 2
    Count of Participants [Participants]
    1
    50%
    0
    0%
    1
    100%
    0
    0%
    1
    50%
    3
    100%
    2
    100%
    3. Secondary Outcome
    Title Maximum Change From Baseline in Blood Pressure
    Description Maximum change from baseline is defined for each participant as the maximum change from baseline value observed across all visits.
    Time Frame Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of conatumumab or ganitumab.
    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg + ganitumab 18 mg/kg once every 3 weeks by intravenous infusion.
    Measure Participants 2 1 1 1 2 3 2
    Systolic blood pressure
    5.5
    (9.2)
    7.0
    54.0
    37.0
    42.0
    (0.0)
    26.0
    (17.3)
    32.5
    (31.8)
    Diastolic blood pressure
    7.5
    (9.2)
    1.0
    10.0
    13.0
    27.5
    (9.2)
    14.7
    (6.4)
    23.5
    (6.4)
    4. Secondary Outcome
    Title Minimum Change From Baseline in Blood Pressure
    Description Minimum change from baseline is defined for each participant as the minimum change from baseline value observed across all visits.
    Time Frame Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of conatumumab or ganitumab.
    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg + ganitumab 18 mg/kg once every 3 weeks by intravenous infusion.
    Measure Participants 2 1 1 1 2 3 2
    Systolic blood pressure
    -28.5
    (17.7)
    -45.0
    -20.0
    -21.0
    -22.5
    (16.3)
    -29.0
    (10.8)
    -12.0
    (12.)
    Diastolic blood pressure
    -19.5
    (9.2)
    -27.0
    -20.0
    -25.0
    -8.5
    (7.8)
    -14.3
    (5.5)
    -10.0
    (4.2)
    5. Secondary Outcome
    Title Number of Participants With CTCAE Grade 3 or Higher Clinical Laboratory Toxicities
    Description Laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
    Time Frame From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of conatumumab or ganitumab.
    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg + ganitumab 18 mg/kg once every 3 weeks by intravenous infusion.
    Measure Participants 2 1 1 1 2 3 2
    Count of Participants [Participants]
    0
    0%
    0
    0%
    1
    100%
    0
    0%
    2
    100%
    2
    66.7%
    1
    50%
    6. Secondary Outcome
    Title Best Overall Response
    Description Radiological assessments to evaluate disease extent (with change compared to nadir from the parent protocol) were performed at regular intervals, at a minimum once every 6 months or more frequently if clinically indicated (starting from their last scan on the parent protocol), per standard of care (SOC) at each facility. Tumor response was assessed by the Investigator as either complete response, partial response, stable disease, or progressive disease.
    Time Frame Approximately every 6 months until end of treatment; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of conatumumab or ganitumab.
    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg + ganitumab 18 mg/kg once every 3 weeks by intravenous infusion.
    Measure Participants 2 1 1 1 2 3 2
    Complete response
    0
    0%
    1
    100%
    0
    0%
    1
    100%
    1
    50%
    0
    0%
    0
    0%
    Partial response
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    50%
    1
    33.3%
    1
    50%
    Stable disease
    2
    100%
    0
    0%
    1
    100%
    0
    0%
    0
    0%
    2
    66.7%
    1
    50%
    Progressive disease
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    7. Secondary Outcome
    Title Number of Participants With Disease Progression or Death Due to Disease Progression
    Description
    Time Frame From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of conatumumab or ganitumab.
    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg + ganitumab 18 mg/kg once every 3 weeks by intravenous infusion.
    Measure Participants 2 1 1 1 2 3 2
    Disease progression
    1
    50%
    1
    100%
    1
    100%
    0
    0%
    2
    100%
    2
    66.7%
    2
    100%
    Death due to disease progression
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    50%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.
    Adverse Event Reporting Description
    Arm/Group Title 20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    Arm/Group Description Ganitumab 20 mg/kg once every 4 weeks by intravenous infusion. Conatumumab 0.45 mg/kg every 2 weeks by intravenous infusion. Conatumumab 3 mg/kg every 3 weeks by intravenous infusion. Conatumumab 5 mg/kg once every 3 weeks by intravenous infusion. Conatumumab 2 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy and bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 10 mg/kg once every 2 weeks by intravenous infusion in addition to modified FOLFOX6 chemotherapy, with or without bevacizumab 5 mg/kg once every 2 weeks. Conatumumab 15 mg/kg + ganitumab 18 mg/kg once every 3 weeks by intravenous infusion.
    All Cause Mortality
    20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    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 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Serious Adverse Events
    20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    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 1/2 (50%) 0/1 (0%) 1/1 (100%) 0/1 (0%) 1/2 (50%) 3/3 (100%) 2/2 (100%)
    Cardiac disorders
    Myocardial infarction 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Diverticular perforation 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Nausea 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Small intestinal obstruction 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Vomiting 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Infections and infestations
    Abdominal wall abscess 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Gastroenteritis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Hepatitis C 0/2 (0%) 0/1 (0%) 1/1 (100%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Pneumonia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 1/2 (50%)
    Injury, poisoning and procedural complications
    Hip fracture 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Metabolism and nutrition disorders
    Hyponatraemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Musculoskeletal and connective tissue disorders
    Lumbar spinal stenosis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Rectal cancer metastatic 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Renal and urinary disorders
    Renal failure 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Haemoptysis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Surgical and medical procedures
    Transurethral bladder resection 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Other (Not Including Serious) Adverse Events
    20050118: Ganitumab 20 mg/kg 20050171: Conatumumab 0.45 mg/kg 20060295: Conatumumab 3 mg/kg 20060340: Conatumumab 5 mg/kg 20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab 20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab 20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
    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 2/2 (100%) 1/1 (100%) 1/1 (100%) 1/1 (100%) 2/2 (100%) 3/3 (100%) 2/2 (100%)
    Blood and lymphatic system disorders
    Anaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 2/3 (66.7%) 1/2 (50%)
    Leukopenia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Lymphopenia 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 1/2 (50%) 1/3 (33.3%) 0/2 (0%)
    Neutropenia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 2/2 (100%) 0/3 (0%) 0/2 (0%)
    Splenomegaly 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Thrombocytopenia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 1/2 (50%)
    Cardiac disorders
    Cardiac flutter 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Cardiomegaly 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Tachycardia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Eye disorders
    Periorbital oedema 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Gastrointestinal disorders
    Abdominal pain 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 2/3 (66.7%) 1/2 (50%)
    Abdominal pain lower 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Diarrhoea 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 2/2 (100%) 1/3 (33.3%) 1/2 (50%)
    Dry mouth 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Dysphagia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Gastrooesophageal reflux disease 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Haematochezia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Lip pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Lip swelling 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Loose tooth 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Nausea 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Oral pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/3 (33.3%) 0/2 (0%)
    Stomatitis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Tooth loss 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Toothache 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/3 (33.3%) 0/2 (0%)
    Vomiting 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    General disorders
    Asthenia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 1/2 (50%)
    Catheter site pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Chills 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Fatigue 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 2/2 (100%) 2/3 (66.7%) 1/2 (50%)
    Gait disturbance 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    General physical health deterioration 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Injection site bruising 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Malaise 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Mucosal inflammation 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Oedema peripheral 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Peripheral swelling 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Pyrexia 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 2/2 (100%) 2/3 (66.7%) 1/2 (50%)
    Swelling 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Systemic inflammatory response syndrome 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Temperature intolerance 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Infections and infestations
    Abdominal infection 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Abdominal wall abscess 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Anal abscess 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Cellulitis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Conjunctivitis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Cystitis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Eyelid infection 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Furuncle 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Hepatitis C 0/2 (0%) 0/1 (0%) 1/1 (100%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Herpes zoster 0/2 (0%) 1/1 (100%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Nasopharyngitis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Peritonitis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Pneumonia 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Postoperative wound infection 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Sinusitis 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Tooth infection 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Upper respiratory tract infection 1/2 (50%) 1/1 (100%) 0/1 (0%) 1/1 (100%) 1/2 (50%) 0/3 (0%) 1/2 (50%)
    Urinary tract infection 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Vaginal infection 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Vulvovaginal mycotic infection 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Injury, poisoning and procedural complications
    Eye contusion 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Eyelid injury 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Fibula fracture 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Humerus fracture 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Ligament sprain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Tooth fracture 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Wound complication 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Investigations
    Amylase increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 2/3 (66.7%) 0/2 (0%)
    Anticoagulation drug level above therapeutic 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Aspartate aminotransferase increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 1/2 (50%)
    Blood alkaline phosphatase increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Blood creatinine increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 2/3 (66.7%) 0/2 (0%)
    Blood magnesium increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Blood phosphorus increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Blood testosterone decreased 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Blood urea increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Blood uric acid increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Chest X-ray abnormal 0/2 (0%) 1/1 (100%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Hepatic enzyme increased 0/2 (0%) 0/1 (0%) 1/1 (100%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    International normalised ratio increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Weight decreased 0/2 (0%) 0/1 (0%) 1/1 (100%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    White blood cell count increased 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    White blood cells urine 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Metabolism and nutrition disorders
    Decreased appetite 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 2/3 (66.7%) 1/2 (50%)
    Dehydration 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 1/2 (50%) 2/3 (66.7%) 1/2 (50%)
    Dyslipidaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Hypercholesterolaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Hyperglycaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Hyperkalaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Hyperlipidaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Hyperuricaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Hypoalbuminaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 1/2 (50%)
    Hypocalcaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Hypokalaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/3 (33.3%) 1/2 (50%)
    Hypomagnesaemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 1/2 (50%)
    Hyponatraemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Hypophosphataemia 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 2/2 (100%)
    Back pain 1/2 (50%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 1/2 (50%) 1/3 (33.3%) 0/2 (0%)
    Bone pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Flank pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Groin pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Intervertebral disc degeneration 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Joint effusion 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Muscular weakness 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Musculoskeletal pain 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Myalgia 0/2 (0%) 1/1 (100%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Pain in extremity 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/3 (33.3%) 0/2 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Lipoma 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Oesophageal carcinoma 0/2 (0%) 0/1 (0%) 1/1 (100%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Squamous cell carcinoma of skin 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Transitional cell carcinoma 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Nervous system disorders
    Dizziness 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Headache 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Hypoaesthesia 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Neuropathy peripheral 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/3 (33.3%) 0/2 (0%)
    Paraesthesia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Seizure 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Syncope 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Tremor 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Product Issues
    Device occlusion 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Psychiatric disorders
    Anxiety 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Confusional state 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Depression 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Libido decreased 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Renal and urinary disorders
    Dysuria 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Nocturia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Reproductive system and breast disorders
    Erectile dysfunction 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Genital rash 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Nipple pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Prostatomegaly 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Vaginal odour 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Vulvovaginal pruritus 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Respiratory, thoracic and mediastinal disorders
    Allergic bronchitis 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Cough 0/2 (0%) 1/1 (100%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Dry throat 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Dysphonia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Dyspnoea 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/3 (33.3%) 0/2 (0%)
    Epistaxis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/3 (33.3%) 0/2 (0%)
    Hypoxia 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Lung infiltration 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Oropharyngeal pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Pleural effusion 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Pleuritic pain 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/3 (33.3%) 0/2 (0%)
    Productive cough 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Pulmonary congestion 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Pulmonary embolism 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 2/3 (66.7%) 0/2 (0%)
    Sleep apnoea syndrome 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Wheezing 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Skin and subcutaneous tissue disorders
    Acne 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Dry skin 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Eczema 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Palmar-plantar erythrodysaesthesia syndrome 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Pruritus 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Rash 0/2 (0%) 1/1 (100%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Rash macular 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Skin hypopigmentation 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Skin lesion 0/2 (0%) 1/1 (100%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 1/2 (50%)
    Surgical and medical procedures
    Micrographic skin surgery 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Skin neoplasm excision 0/2 (0%) 1/1 (100%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/3 (0%) 0/2 (0%)
    Tooth extraction 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 2/3 (66.7%) 0/2 (0%)
    Vascular disorders
    Deep vein thrombosis 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Hot flush 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    Hypertension 0/2 (0%) 0/1 (0%) 0/1 (0%) 1/1 (100%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Hypotension 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/3 (33.3%) 0/2 (0%)
    May-Thurner syndrome 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)
    Peripheral venous disease 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/3 (0%) 0/2 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.

    Results Point of Contact

    Name/Title Study Director
    Organization Amgen Inc.
    Phone 866-572-6436
    Email medinfo@amgen.com
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01327612
    Other Study ID Numbers:
    • 20101116
    • 2010-022270-14
    First Posted:
    Apr 1, 2011
    Last Update Posted:
    Feb 21, 2021
    Last Verified:
    Feb 1, 2021