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Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma

Sponsor
Gilead Sciences (Industry)
Overall Status
Terminated
CT.gov ID
NCT01479465
Collaborator
(none)
266
Enrollment
109
Locations
4
Arms
38
Actual Duration (Months)
2.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to compare the additive efficacy of SIM versus placebo in combination with leucovorin (folinic acid), irinotecan, and fluorouracil (FOLFIRI) as measured by improvement in progression-free survival (PFS) in participants with metastatic KRAS mutant colorectal adenocarcinoma who have progressed following a first-line oxaliplatin- and fluoropyrimidine-containing regimen.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
266 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-6624 Combined With FOLFIRI as Second Line Treatment for Metastatic KRAS Mutant Colorectal Adenocarcinoma That Has Progressed Following a First Line Oxaliplatin- and Fluoropyrimidine-Containing Regimen
Actual Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Oct 1, 2014
Actual Study Completion Date :
Feb 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: FOLFIRI + SIM 700 mg (Part A)

Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.

Biological: Simtuzumab
SIM administered via intravenous infusion over 30 minutes
Other Names:
  • SIM; GS-6624

    • Drug: Leucovorin
    l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
    Other Names:
  • Folinic acid

    • Drug: Irinotecan
    Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes

    Drug: Fluorouracil
    Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours
    Experimental: FOLFIRI + SIM 200 mg (Part B)

    Participants will receive SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.

    Biological: Simtuzumab
    SIM administered via intravenous infusion over 30 minutes
    Other Names:
  • SIM; GS-6624

    • Drug: Leucovorin
    l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
    Other Names:
  • Folinic acid

    • Drug: Irinotecan
    Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes

    Drug: Fluorouracil
    Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours
    Experimental: FOLFIRI + SIM 700 mg (Part B)

    Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.

    Biological: Simtuzumab
    SIM administered via intravenous infusion over 30 minutes
    Other Names:
  • SIM; GS-6624

    • Drug: Leucovorin
    l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
    Other Names:
  • Folinic acid

    • Drug: Irinotecan
    Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes

    Drug: Fluorouracil
    Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours
    Experimental: FOLFIRI + Placebo (Part B)

    Participants will receive placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.

    Drug: Placebo to match SIM
    Placebo to match SIM administered via intravenous infusion over 30 minutes

    Drug: Leucovorin
    l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
    Other Names:
  • Folinic acid

    • Drug: Irinotecan
    Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes

    Drug: Fluorouracil
    Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [Randomization up to 27 months]

      The PFS was defined as the time from the date of randomization to the earliest event time of: a) death regardless of cause, or b) first indication of disease progression. PFS was analyzed using Kaplan-Meier (KM) estimates.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Randomization up to 33 months]

      The OS is measured as time from date of randomization to death regardless of cause. The OS was analyzed using KM estimates.

    2. Objective Response Rate (ORR) [Randomization up to 27 months]

      Objective response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). The ORR was defined as the percentage of participants who achieved a CR or PR.

    Eligibility Criteria

    Criteria

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

    • Metastatic colorectal carcinoma with KRAS mutation

    • Received first line therapy and discontinued part or all of first line therapy

    • Estimated life expectancy > 3 months

    • Stage IV disease

    • Eastern Cooperative Oncology Group (ECOG) performance status: 0-2

    • Adequate hepatic and hematologic function

    • No major operations within 4 weeks prior to treatment start

    Exclusion Criteria:

    • More than 1 prior chemotherapy regimen for Stage 4 colorectal cancer

    • Experimental medical treatment within 30 days prior to study entry

    • Known or suspected cerebral metastases

    • History or presence of any form of cancer, other that colorectal cancer, within the 3 years prior to enrollment

    • Known dihydropyrimidine dehydrogenase-deficiency (special screening not required)

    • Subjects with angina pectoris, poorly controlled ventricular arrhythmias (does not include asymptomatic, occasional premature ventricular contractions), history of clinically significant coronary heart disease or cardiomyopathy, or electrocardiogram (ECG) abnormalities consistent with ischemia

    • Uncontrolled hypertension (seated systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg) at screening

    • Clinically active liver disease, including active hepatitis (any etiology) or cirrhosis

    • Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) within 21 days prior to randomization

    • Prior irinotecan therapy for metastatic disease is not permitted

    • Systemic fungal, bacterial, viral, or other infection

    Note: Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clearview Cancer Institute Huntsville Alabama United States 35801
    2 Banner MD Anderson Cancer Center Gilbert Arizona United States
    3 Central Hematology Oncology Medical Group, Inc. Alhambra California United States
    4 Comprehensive Blood and Cancer Center Bakersfield California United States
    5 Providence Saint Joseph Medical Center-Disney Family Cancer Center Burbank California United States
    6 Wilshire Oncology Medical Group, Inc. Corona California United States
    7 Saint Jude Heritage Healthcare Fullerton California United States
    8 University of California San Diego Medical Center La Jolla California United States
    9 Pacific Shores Medical Group Long Beach California United States
    10 Comprehensive Hematology Oncology Centers, Inc. Los Angeles California United States
    11 TORI Network (Translational Oncology Research Intl) Los Angeles California United States
    12 UCLA Community Oncology Practice Los Angeles California United States
    13 Stanford University Medical Center Palo Alto California United States
    14 Wilshire Oncology Medical Group, Inc. Pomona California United States
    15 Cancer Care Associates Medical Group Redondo Beach California United States
    16 Pacific Shores Medical Group Redondo Beach California United States
    17 Sharp Health Care San Diego California United States
    18 San Jose Medical Group San Jose California United States
    19 Central Coast Medical Oncology Corp Santa Maria California United States
    20 Yale University Smilow Cancer Hospital New Haven Connecticut United States 06520
    21 Georgetown University Washington District of Columbia United States
    22 Florida Cancer Specialists Gainesville Florida United States
    23 MD Anderson Cancer Center Orlando Florida United States
    24 Florida Cancer Specialists Saint Petersburg Florida United States
    25 Peachtree Hematology Oncology Consultants, PC Atlanta Georgia United States
    26 Suburban Hematology Oncology Associates, PC Lawrenceville Georgia United States
    27 Northwestern University Chicago Illinois United States
    28 Indiana University Simon Cancer Center Indianapolis Indiana United States
    29 Tufts Medical Center Boston Massachusetts United States 02111
    30 Dana Farber Cancer Institute Boston Massachusetts United States
    31 West Michigan Cancer Center Kalamazoo Michigan United States
    32 Hematology and Oncology Associates at BridgePoint Tupelo Mississippi United States
    33 Saint Joseph Oncology, Inc. Saint Joseph Missouri United States
    34 Montana Cancer Institute Missoula Montana United States 59802
    35 Southeast Nebraska Cancer Center Lincoln Nebraska United States
    36 Comprehensive Cancer Centers of Nevada Henderson Nevada United States
    37 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States
    38 New York University Clinical Cancer Center New York New York United States 10016
    39 Oncology Hematology Care, Inc. Cincinnati Ohio United States
    40 Signal Point Clinical Research Center, LLC Middletown Ohio United States
    41 Oncology Hematology Care, Inc. Wilmington Ohio United States
    42 Kaiser Permanente Northwest Region Oncology Hematology Portland Oregon United States
    43 South Carolina Oncology Associates Columbia South Carolina United States
    44 Tennessee Oncology, PLLC Nashville Tennessee United States
    45 University of Texas Southwestern Medical Center at Dallas Dallas Texas United States
    46 Center for Cancer and Blood Disorders, PC Fort Worth Texas United States
    47 Joe Arrington Cancer Research and Treatment Center Lubbock Texas United States
    48 Scott & White Memorial Temple Texas United States 76508
    49 The Center for Cancer and Blood Disorders Weatherford Texas United States
    50 Intermountain Healthcare Saint George Utah United States
    51 Utah Cancer Specialists Salt Lake City Utah United States
    52 Virginal Cancer Specialists, PC Fairfax Virginia United States 22033
    53 Virginia Cancer Institute Midlothian Virginia United States
    54 Virginia Cancer Institute Richmond Virginia United States
    55 Seattle Cancer Care Alliance Seattle Washington United States
    56 University of Wisconsin Madison Wisconsin United States
    57 Centre Hospitalier Universitaire Estaing Clermont Ferrand Auvergne France 63003
    58 Centre Eugène Marquis Rennes Cedex Bretagne France 35042
    59 Centre Georges François Leclerc Dijon France
    60 Centre Oscar Lambret, Dept. de Cancerologie Digestive et Urologique Lille Cedex France
    61 Centre Hospitalier Régional Universitaire Hôpital Saint Eloi Montpellier Cedex 5 France
    62 Centre Antoine Lacassagne Nice Cedex 2 France
    63 Institut Paoli Calmettes Centre Régional de Lutte Contre le Cancer Rennes Cedex France
    64 Hôpital Trousseau - Service de Gastroenterologie Tours France
    65 Universitätsklinikum Ulm Ulm Baden-Wuerttemberg Germany 89081
    66 Universitätsklinikums Mannheim Mannheim Baden-Wuerttenberg Germany 68167
    67 Ludwig-Maximilians-Universität München Klinikum Großhadern München Bayern Germany 81377
    68 Universitätsklinikum Rostock Rostock Mecklenburg-Vorpommern Germany 18055
    69 Klinikum Region Hannover GmbH, Krankenhaus Siloah Hannover Niedersachsen Germany 30449
    70 Medizinische Universitätsklinik Bochum Bochum Nordrhein-Westfalen Germany 44892
    71 Universitätsklinikum Essen Essen Nordrhein-Westfalen Germany 45122
    72 Krankenanstalt Mutterhaus der Borromäerinnen e.V. Trier Rheinland-Pfalz Germany 54290
    73 Universitätsklinikum Dresden Dresden Sachsen Germany 01307
    74 Universitätsklinikum der Friedrich-Schiller-Universität Jena Jena Thuringen Germany 07747
    75 Städtisches Klinikum Frankfurt-Höchst Frankfurt Germany
    76 Katholisches Marienkrankenhaus gGmbH Hamburg Germany 22045
    77 University Magdeburg Magdeburg Germany
    78 Ospedale Unico Versilia Lido di Camaiore Lucca Italy 55043
    79 Azienda Ospedaliera San Gerardo di Monza Monza Monza E Brianza Italy 20052
    80 Arcispedale Santa Maria Nuova IRCCS Reggio Emilia Reggio Nella Emilia Italy 42100
    81 Istituto Europeo di Oncologia Milano Italy 20141
    82 Ospedale Niguarda Cà Granda Milano Italy 20162
    83 Ospedale Civile SS Annunziata ASL 1 Sassari Italy 07100
    84 Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Spólka z o. o. Kraków Malopolskie Poland 31-826
    85 Uniwersyteckie Centrum Kliniczne Gdansk Pomorskie Poland 80-952
    86 Olsztynski Osrodek Onkologiczny "Kopernik" sp. z o. o. Olsztyn Warminsko-Mazurskie Poland 10-513
    87 Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy Bydgoszcz Poland
    88 Centralny Szpital Kliniczny MSWiA Warszawa Poland
    89 Centrum Onkologii - Instytut im Marii Sklodowskiej-Curie Warszawa Poland
    90 State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary" Arkhangelsk Russian Federation
    91 Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan Kazan Russian Federation
    92 Kursk Regional Oncologic Dispensary Kursk Russian Federation
    93 Cancer Research Center n.a. Blokhin, Chemotherapy Dept. Moscow Russian Federation
    94 Non-State Institution of healthcare "Central Clinical Hospital #1 OAO RZD" Moscow Russian Federation
    95 State Institution "Blokhin Cancer Research Centre RAMS" Moscow Russian Federation
    96 Nizhny Novgorod City Oncology Dispensary Nizhny Novgorod Russian Federation
    97 State Healthcare Institution of Omsk Region "Clinical Oncologic Dispensary" Omsk Russian Federation
    98 N.N.Petrov Research Institute of Oncology Saint Petersburg Russian Federation
    99 Centro Oncológico Regional de Galicia A Coruña La Coruna Spain 15009
    100 Hospital Nuestra Señora de Sonsoles Avila Spain 05004
    101 Hospital Universitario Vall d'Hebron Barcelona Spain 08035
    102 Hospital Universitario de Girona Doctor Josep Trueta Gerona Spain 17007
    103 Hospital Universitario Ramón y Cajal Madrid Spain 28034
    104 Hospital Clinico Universitario San Carlos Madrid Spain 28040
    105 Hospital Universitario 12 de Octubre Madrid Spain 28041
    106 Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro Madrid Spain 28050
    107 Hospital Universitario La Paz Madrid Spain
    108 Instituto de Investigación Sanitaria Madrid Spain
    109 Hospital Clinico Universitario de Valencia Valencia Spain 46010

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Zung Thai, MD, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01479465
    Other Study ID Numbers:
    • GS-US-295-0203
    • 2011-003754-61
    First Posted:
    Nov 24, 2011
    Last Update Posted:
    Apr 17, 2019
    Last Verified:
    Mar 1, 2019
    Keywords provided by Gilead Sciences
    GSI
    Gilead
    Gilead Sciences
    GS-6624
    Colorectal Cancer
    KRAS
    Oncology
    monoclonal antibody
    Additional relevant MeSH terms:
    Colorectal Neoplasms
    Adenocarcinoma
    Leucovorin
    Fluorouracil
    Irinotecan

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in the United States, Russia, and Europe. The first participant was screened on 15 December 2011. The last study visit occurred on 27 February 2015.
    Pre-assignment Detail 358 participants were screened.
    Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
    Arm/Group Description Participants received simtuzumab (SIM) 700 mg via intravenous infusion followed by leucovorin (folinic acid), irinotecan, and fluorouracil (FOLFIRI; l-leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours and irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes, followed by fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours) on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months. Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months. Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months. Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
    Period Title: Overall Study
    STARTED 11 84 86 85
    COMPLETED 0 0 0 0
    NOT COMPLETED 11 84 86 85

    Baseline Characteristics

    Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B) Total
    Arm/Group Description Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months. Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months. Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months. Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months. Total of all reporting groups
    Overall Participants 11 84 86 85 266
    Age, Customized (Count of Participants)
    Between 18 and 65 years
    7
    63.6%
    57
    67.9%
    49
    57%
    56
    65.9%
    169
    63.5%
    ≥ 65 years
    4
    36.4%
    23
    27.4%
    36
    41.9%
    28
    32.9%
    91
    34.2%
    Sex: Female, Male (Count of Participants)
    Female
    6
    54.5%
    41
    48.8%
    32
    37.2%
    48
    56.5%
    127
    47.7%
    Male
    5
    45.5%
    39
    46.4%
    53
    61.6%
    36
    42.4%
    133
    50%
    Race/Ethnicity, Customized (Count of Participants)
    White
    8
    72.7%
    67
    79.8%
    74
    86%
    71
    83.5%
    220
    82.7%
    Black or African American
    2
    18.2%
    8
    9.5%
    5
    5.8%
    7
    8.2%
    22
    8.3%
    Asian
    1
    9.1%
    1
    1.2%
    5
    5.8%
    1
    1.2%
    8
    3%
    Native Hawaiian or Pacific Islander
    0
    0%
    1
    1.2%
    0
    0%
    1
    1.2%
    2
    0.8%
    Not Permitted
    0
    0%
    3
    3.6%
    1
    1.2%
    3
    3.5%
    7
    2.6%
    Missing
    0
    0%
    0
    0%
    0
    0%
    1
    1.2%
    1
    0.4%
    Race/Ethnicity, Customized (Count of Participants)
    Non-Hispanic/Latino
    8
    72.7%
    70
    83.3%
    75
    87.2%
    73
    85.9%
    226
    85%
    Hispanic/Latino
    3
    27.3%
    5
    6%
    7
    8.1%
    8
    9.4%
    23
    8.6%
    Not Permitted
    0
    0%
    5
    6%
    3
    3.5%
    3
    3.5%
    11
    4.1%
    Region of Enrollment (Count of Participants)
    United States
    11
    100%
    45
    53.6%
    47
    54.7%
    45
    52.9%
    148
    55.6%
    Poland
    0
    0%
    5
    6%
    7
    8.1%
    5
    5.9%
    17
    6.4%
    Italy
    0
    0%
    7
    8.3%
    7
    8.1%
    4
    4.7%
    18
    6.8%
    France
    0
    0%
    4
    4.8%
    1
    1.2%
    3
    3.5%
    8
    3%
    Germany
    0
    0%
    5
    6%
    4
    4.7%
    7
    8.2%
    16
    6%
    Spain
    0
    0%
    9
    10.7%
    13
    15.1%
    8
    9.4%
    30
    11.3%
    Russia
    0
    0%
    9
    10.7%
    7
    8.1%
    13
    15.3%
    29
    10.9%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival (PFS)
    Description The PFS was defined as the time from the date of randomization to the earliest event time of: a) death regardless of cause, or b) first indication of disease progression. PFS was analyzed using Kaplan-Meier (KM) estimates.
    Time Frame Randomization up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set included participants who were randomized and received at least 1 dose of study drug.
    Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
    Arm/Group Description Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months. Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months. Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months. Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
    Measure Participants 11 80 85 84
    Median (95% Confidence Interval) [months]
    5.7
    5.8
    5.4
    5.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection FOLFIRI + Placebo (Part B), FOLFIRI + SIM 200 mg (Part B)
    Comments The null hypothesis was that the hazard ratio (HR) equals to 1 between SIM treatment arm and placebo, while the alternative hypothesis was that HR was less than 1. The HR (95% confidence interval [CI]) and p-value (for comparison between SIM treatment arm and placebo) were based on two-sided log-rank test, stratified based on the 2-level Eastern Cooperative Oncology Group (ECOG) performance status (0 or > 0) at randomization.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0395
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.45
    Confidence Interval (2-Sided) 95%
    1.01 to 2.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection FOLFIRI + Placebo (Part B), FOLFIRI + SIM 700 mg (Part B)
    Comments The null hypothesis was that the HR equals to 1 between SIM treatment arm and placebo, while the alternative hypothesis was that HR was less than 1. The HR (95% CI) and p-value (for comparison between SIM treatment arm and placebo) were based on two-sided log-rank test, stratified based on the 2-level ECOG performance status (0 or > 0) at randomization.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1042
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.32
    Confidence Interval (2-Sided) 95%
    0.92 to 1.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Overall Survival (OS)
    Description The OS is measured as time from date of randomization to death regardless of cause. The OS was analyzed using KM estimates.
    Time Frame Randomization up to 33 months

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
    Arm/Group Description Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months. Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months. Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months. Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
    Measure Participants 11 80 85 84
    Median (95% Confidence Interval) [months]
    9.8
    16.3
    10.5
    11.4
    3. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description Objective response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). The ORR was defined as the percentage of participants who achieved a CR or PR.
    Time Frame Randomization up to 27 months

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
    Arm/Group Description Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months. Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months. Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months. Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
    Measure Participants 11 80 85 84
    Number (95% Confidence Interval) [percentage of participants]
    9.1
    82.7%
    10.0
    11.9%
    5.9
    6.9%
    11.9
    14%

    Adverse Events

    Time Frame Randomization up to 33 months
    Adverse Event Reporting Description Safety Analysis Set included all participants in the Full Analysis Set grouped for analyses with treatment assignments designated according to the actual study drug received.
    Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
    Arm/Group Description Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months. Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months. Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months. Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
    All Cause Mortality
    FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/11 (36.4%) 27/80 (33.8%) 24/85 (28.2%) 17/84 (20.2%)
    Blood and lymphatic system disorders
    Anaemia 1/11 (9.1%) 0/80 (0%) 1/85 (1.2%) 3/84 (3.6%)
    Febrile neutropenia 0/11 (0%) 2/80 (2.5%) 3/85 (3.5%) 1/84 (1.2%)
    Leukopenia 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 1/84 (1.2%)
    Neutropenia 0/11 (0%) 3/80 (3.8%) 1/85 (1.2%) 2/84 (2.4%)
    Thrombocytopenia 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 1/84 (1.2%)
    Cardiac disorders
    Acute coronary syndrome 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Atrial fibrillation 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Cardiac arrest 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Cardiac failure 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Tachycardia 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Gastrointestinal disorders
    Abdominal pain 1/11 (9.1%) 2/80 (2.5%) 0/85 (0%) 1/84 (1.2%)
    Anal fistula 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Diarrhoea 0/11 (0%) 1/80 (1.3%) 3/85 (3.5%) 0/84 (0%)
    Enteritis 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Intestinal obstruction 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 2/84 (2.4%)
    Intestinal perforation 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Large intestinal obstruction 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 1/84 (1.2%)
    Nausea 0/11 (0%) 2/80 (2.5%) 0/85 (0%) 1/84 (1.2%)
    Small intestinal obstruction 0/11 (0%) 1/80 (1.3%) 1/85 (1.2%) 0/84 (0%)
    Subileus 0/11 (0%) 2/80 (2.5%) 0/85 (0%) 0/84 (0%)
    Vomiting 0/11 (0%) 3/80 (3.8%) 2/85 (2.4%) 1/84 (1.2%)
    General disorders
    Asthenia 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Death 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    General physical health deterioration 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Pyrexia 0/11 (0%) 0/80 (0%) 0/85 (0%) 2/84 (2.4%)
    Immune system disorders
    Hypersensitivity 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Infections and infestations
    Bacteraemia 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Device related infection 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 1/84 (1.2%)
    Diverticulitis 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Gastroenteritis 0/11 (0%) 2/80 (2.5%) 0/85 (0%) 0/84 (0%)
    Gastroenteritis viral 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Herpes zoster 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Influenza 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Klebsiella infection 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Lung infection 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Pneumonia 0/11 (0%) 2/80 (2.5%) 0/85 (0%) 1/84 (1.2%)
    Pyelonephritis 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Respiratory tract infection 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Sepsis 1/11 (9.1%) 1/80 (1.3%) 0/85 (0%) 3/84 (3.6%)
    Urinary tract infection 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Urosepsis 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 1/84 (1.2%)
    Injury, poisoning and procedural complications
    Ankle fracture 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Hip fracture 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Post procedural haemorrhage 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Radius fracture 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Investigations
    Neutrophil count decreased 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Urine output decreased 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/11 (0%) 2/80 (2.5%) 1/85 (1.2%) 0/84 (0%)
    Diabetic ketoacidosis 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Electrolyte imbalance 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Hypoglycaemia 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Hypokalaemia 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 1/84 (1.2%)
    Hyponatraemia 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Hypophosphataemia 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant ascites 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Metastases to central nervous system 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Tumour thrombosis 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Nervous system disorders
    Cerebrovascular accident 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Presyncope 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Psychiatric disorders
    Confusional state 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 1/84 (1.2%)
    Delirium 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Mental status changes 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Renal and urinary disorders
    Nephrolithiasis 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Renal failure acute 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Renal impairment 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Urinary tract disorder 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Lower respiratory tract inflammation 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Pneumothorax 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Pulmonary embolism 0/11 (0%) 4/80 (5%) 2/85 (2.4%) 2/84 (2.4%)
    Pulmonary infarction 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Respiratory failure 0/11 (0%) 0/80 (0%) 0/85 (0%) 1/84 (1.2%)
    Vascular disorders
    Deep vein thrombosis 0/11 (0%) 0/80 (0%) 1/85 (1.2%) 1/84 (1.2%)
    Superior vena cava occlusion 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Venous thrombosis 0/11 (0%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Other (Not Including Serious) Adverse Events
    FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/11 (100%) 76/80 (95%) 80/85 (94.1%) 79/84 (94%)
    Blood and lymphatic system disorders
    Anaemia 3/11 (27.3%) 19/80 (23.8%) 23/85 (27.1%) 18/84 (21.4%)
    Leukopenia 1/11 (9.1%) 9/80 (11.3%) 13/85 (15.3%) 13/84 (15.5%)
    Neutropenia 6/11 (54.5%) 35/80 (43.8%) 42/85 (49.4%) 40/84 (47.6%)
    Thrombocytopenia 0/11 (0%) 6/80 (7.5%) 10/85 (11.8%) 11/84 (13.1%)
    Cardiac disorders
    Arrhythmia 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Atrial fibrillation 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Cardiac failure congestive 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Palpitations 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Eye disorders
    Eye pain 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Ocular hyperaemia 1/11 (9.1%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 1/11 (9.1%) 2/80 (2.5%) 2/85 (2.4%) 0/84 (0%)
    Abdominal distension 2/11 (18.2%) 4/80 (5%) 2/85 (2.4%) 1/84 (1.2%)
    Abdominal pain 4/11 (36.4%) 18/80 (22.5%) 16/85 (18.8%) 22/84 (26.2%)
    Abdominal pain lower 0/11 (0%) 5/80 (6.3%) 0/85 (0%) 2/84 (2.4%)
    Abdominal pain upper 2/11 (18.2%) 6/80 (7.5%) 8/85 (9.4%) 6/84 (7.1%)
    Constipation 4/11 (36.4%) 17/80 (21.3%) 18/85 (21.2%) 21/84 (25%)
    Diarrhoea 9/11 (81.8%) 43/80 (53.8%) 36/85 (42.4%) 42/84 (50%)
    Dry mouth 1/11 (9.1%) 7/80 (8.8%) 2/85 (2.4%) 3/84 (3.6%)
    Dyspepsia 3/11 (27.3%) 7/80 (8.8%) 4/85 (4.7%) 4/84 (4.8%)
    Dysphagia 2/11 (18.2%) 4/80 (5%) 0/85 (0%) 1/84 (1.2%)
    Gastrooesophageal reflux disease 2/11 (18.2%) 3/80 (3.8%) 3/85 (3.5%) 1/84 (1.2%)
    Haematochezia 1/11 (9.1%) 2/80 (2.5%) 1/85 (1.2%) 0/84 (0%)
    Nausea 9/11 (81.8%) 37/80 (46.3%) 38/85 (44.7%) 42/84 (50%)
    Oral mucosal erythema 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Oral pain 1/11 (9.1%) 2/80 (2.5%) 3/85 (3.5%) 1/84 (1.2%)
    Salivary hypersecretion 2/11 (18.2%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Stomatitis 1/11 (9.1%) 17/80 (21.3%) 14/85 (16.5%) 9/84 (10.7%)
    Vomiting 5/11 (45.5%) 25/80 (31.3%) 21/85 (24.7%) 23/84 (27.4%)
    General disorders
    Asthenia 2/11 (18.2%) 12/80 (15%) 13/85 (15.3%) 12/84 (14.3%)
    Axillary pain 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Catheter site pain 1/11 (9.1%) 1/80 (1.3%) 0/85 (0%) 1/84 (1.2%)
    Catheter site rash 1/11 (9.1%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Chest discomfort 1/11 (9.1%) 1/80 (1.3%) 0/85 (0%) 1/84 (1.2%)
    Chest pain 0/11 (0%) 3/80 (3.8%) 1/85 (1.2%) 5/84 (6%)
    Fatigue 9/11 (81.8%) 34/80 (42.5%) 38/85 (44.7%) 43/84 (51.2%)
    Feeling abnormal 1/11 (9.1%) 0/80 (0%) 1/85 (1.2%) 0/84 (0%)
    Feeling jittery 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Malaise 1/11 (9.1%) 1/80 (1.3%) 1/85 (1.2%) 5/84 (6%)
    Mucosal inflammation 3/11 (27.3%) 10/80 (12.5%) 14/85 (16.5%) 7/84 (8.3%)
    Oedema peripheral 0/11 (0%) 4/80 (5%) 14/85 (16.5%) 10/84 (11.9%)
    Pyrexia 1/11 (9.1%) 11/80 (13.8%) 10/85 (11.8%) 11/84 (13.1%)
    Infections and infestations
    Infection 1/11 (9.1%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Nasopharyngitis 1/11 (9.1%) 1/80 (1.3%) 2/85 (2.4%) 2/84 (2.4%)
    Pneumonia 1/11 (9.1%) 2/80 (2.5%) 2/85 (2.4%) 0/84 (0%)
    Respiratory tract infection 1/11 (9.1%) 1/80 (1.3%) 1/85 (1.2%) 0/84 (0%)
    Upper respiratory tract infection 0/11 (0%) 5/80 (6.3%) 4/85 (4.7%) 2/84 (2.4%)
    Urinary tract infection 0/11 (0%) 6/80 (7.5%) 5/85 (5.9%) 9/84 (10.7%)
    Investigations
    Alanine aminotransferase increased 0/11 (0%) 4/80 (5%) 4/85 (4.7%) 5/84 (6%)
    Aspartate aminotransferase increased 0/11 (0%) 5/80 (6.3%) 6/85 (7.1%) 4/84 (4.8%)
    Blood alkaline phosphatase increased 1/11 (9.1%) 6/80 (7.5%) 4/85 (4.7%) 4/84 (4.8%)
    International normalised ratio increased 1/11 (9.1%) 2/80 (2.5%) 2/85 (2.4%) 1/84 (1.2%)
    Neutrophil count decreased 0/11 (0%) 5/80 (6.3%) 3/85 (3.5%) 3/84 (3.6%)
    Weight decreased 1/11 (9.1%) 7/80 (8.8%) 9/85 (10.6%) 6/84 (7.1%)
    White blood cell count increased 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 5/11 (45.5%) 22/80 (27.5%) 14/85 (16.5%) 21/84 (25%)
    Dehydration 3/11 (27.3%) 4/80 (5%) 5/85 (5.9%) 6/84 (7.1%)
    Hyperglycaemia 1/11 (9.1%) 2/80 (2.5%) 4/85 (4.7%) 3/84 (3.6%)
    Hypoalbuminaemia 1/11 (9.1%) 0/80 (0%) 1/85 (1.2%) 1/84 (1.2%)
    Hypocalcaemia 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 2/84 (2.4%)
    Hypokalaemia 0/11 (0%) 8/80 (10%) 8/85 (9.4%) 10/84 (11.9%)
    Hypomagnesaemia 0/11 (0%) 5/80 (6.3%) 2/85 (2.4%) 3/84 (3.6%)
    Hypophosphataemia 1/11 (9.1%) 1/80 (1.3%) 2/85 (2.4%) 2/84 (2.4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/11 (9.1%) 4/80 (5%) 4/85 (4.7%) 5/84 (6%)
    Back pain 3/11 (27.3%) 6/80 (7.5%) 9/85 (10.6%) 9/84 (10.7%)
    Bone pain 1/11 (9.1%) 2/80 (2.5%) 0/85 (0%) 2/84 (2.4%)
    Muscle atrophy 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Muscle spasms 1/11 (9.1%) 5/80 (6.3%) 0/85 (0%) 5/84 (6%)
    Muscle tightness 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Muscular weakness 2/11 (18.2%) 0/80 (0%) 2/85 (2.4%) 0/84 (0%)
    Musculoskeletal pain 1/11 (9.1%) 3/80 (3.8%) 1/85 (1.2%) 5/84 (6%)
    Pain in extremity 1/11 (9.1%) 3/80 (3.8%) 1/85 (1.2%) 6/84 (7.1%)
    Nervous system disorders
    Dizziness 1/11 (9.1%) 7/80 (8.8%) 9/85 (10.6%) 13/84 (15.5%)
    Dizziness postural 1/11 (9.1%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Dysgeusia 1/11 (9.1%) 6/80 (7.5%) 6/85 (7.1%) 8/84 (9.5%)
    Headache 1/11 (9.1%) 4/80 (5%) 3/85 (3.5%) 6/84 (7.1%)
    Neuropathy peripheral 2/11 (18.2%) 5/80 (6.3%) 7/85 (8.2%) 7/84 (8.3%)
    Parosmia 1/11 (9.1%) 1/80 (1.3%) 1/85 (1.2%) 0/84 (0%)
    Peripheral sensory neuropathy 1/11 (9.1%) 4/80 (5%) 2/85 (2.4%) 3/84 (3.6%)
    VIIth nerve paralysis 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Psychiatric disorders
    Agitation 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Anger 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Anxiety 3/11 (27.3%) 5/80 (6.3%) 5/85 (5.9%) 4/84 (4.8%)
    Depression 1/11 (9.1%) 2/80 (2.5%) 3/85 (3.5%) 3/84 (3.6%)
    Insomnia 5/11 (45.5%) 9/80 (11.3%) 5/85 (5.9%) 8/84 (9.5%)
    Mood swings 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Renal and urinary disorders
    Dysuria 0/11 (0%) 5/80 (6.3%) 3/85 (3.5%) 0/84 (0%)
    Micturition urgency 1/11 (9.1%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Nocturia 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Cough 1/11 (9.1%) 10/80 (12.5%) 10/85 (11.8%) 14/84 (16.7%)
    Dyspnoea 0/11 (0%) 10/80 (12.5%) 9/85 (10.6%) 11/84 (13.1%)
    Dyspnoea exertional 1/11 (9.1%) 0/80 (0%) 3/85 (3.5%) 0/84 (0%)
    Epistaxis 0/11 (0%) 10/80 (12.5%) 5/85 (5.9%) 4/84 (4.8%)
    Hiccups 2/11 (18.2%) 1/80 (1.3%) 1/85 (1.2%) 1/84 (1.2%)
    Oropharyngeal pain 1/11 (9.1%) 3/80 (3.8%) 0/85 (0%) 8/84 (9.5%)
    Rhinorrhoea 1/11 (9.1%) 2/80 (2.5%) 2/85 (2.4%) 4/84 (4.8%)
    Throat tightness 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 6/11 (54.5%) 21/80 (26.3%) 20/85 (23.5%) 22/84 (26.2%)
    Dry skin 0/11 (0%) 5/80 (6.3%) 2/85 (2.4%) 5/84 (6%)
    Hyperhidrosis 1/11 (9.1%) 3/80 (3.8%) 2/85 (2.4%) 3/84 (3.6%)
    Night sweats 0/11 (0%) 4/80 (5%) 1/85 (1.2%) 3/84 (3.6%)
    Rash 1/11 (9.1%) 3/80 (3.8%) 4/85 (4.7%) 3/84 (3.6%)
    Skin disorder 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Skin hyperpigmentation 1/11 (9.1%) 1/80 (1.3%) 2/85 (2.4%) 2/84 (2.4%)
    Skin wrinkling 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)
    Swelling face 1/11 (9.1%) 1/80 (1.3%) 0/85 (0%) 0/84 (0%)
    Vascular disorders
    Flushing 2/11 (18.2%) 0/80 (0%) 2/85 (2.4%) 0/84 (0%)
    Hypotension 1/11 (9.1%) 3/80 (3.8%) 2/85 (2.4%) 4/84 (4.8%)
    Peripheral coldness 1/11 (9.1%) 0/80 (0%) 0/85 (0%) 0/84 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01479465
    Other Study ID Numbers:
    • GS-US-295-0203
    • 2011-003754-61
    First Posted:
    Nov 24, 2011
    Last Update Posted:
    Apr 17, 2019
    Last Verified:
    Mar 1, 2019