Clincosm LogoSign in Get a demo

ASPIRE: A Safety and Effectiveness Study of TMC435 in Chronic, Genotype 1, Hepatitis C Patients Who Failed to Previous Standard Treatment

Sponsor
Tibotec Pharmaceuticals, Ireland (Industry)
Overall Status
Completed
CT.gov ID
NCT00980330
Collaborator
(none)
463
Enrollment
81
Locations
7
Arms
22
Duration (Months)
5.7
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV).

Condition or Disease Intervention/Treatment Phase
  • Drug: TMC435
  • Drug: Placebo
  • Drug: Peg-IFN-alfa-2a (P)
  • Drug: Ribavirin (R)
 Phase 2

Detailed Description

The study is a randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled Phase IIb trial with TMC435 in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who have failed standard treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV). The study will compare the efficacy, tolerability and safety of different regimens with TMC435 combined with standard treatment (Peg-INF-alfa-2a and RBV) versus standard treatment alone. The trial will consist of a screening period of maximum 6 weeks, a 48-week treatment period, and a 24-week follow-up period. Participants will be eligible to enroll in the trial if they failed to respond to a prior course of standard treatment or relapsed following standard treatment. Participants will be randomly assigned to receive TMC435 with standard treatment for 12 weeks followed by standard treatment (plus placebo) for 36 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 24 weeks followed by standard treatment (plus placebo) for 24 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 48 weeks, or a placebo with standard treatment for 48 weeks.

Study Design

Study Type:
Interventional
Actual Enrollment :
463 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy
Study Start Date :
Oct 1, 2009
Actual Primary Completion Date :
Aug 1, 2011
Actual Study Completion Date :
Aug 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: TMC435 100 mg 12 Wks + PR48

Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks.

Drug: TMC435
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Drug: Placebo
One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

Drug: Peg-IFN-alfa-2a (P)
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
Other Names:
  • PEGASYS

    • Drug: Ribavirin (R)
    1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
    Other Names:
  • COPEGUS

    		•
    Experimental: TMC435 100 mg 24 Wks + PR48

    Participants willl receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks.

    Drug: TMC435
    One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

    Drug: Placebo
    One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

    Drug: Peg-IFN-alfa-2a (P)
    180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
    Other Names:
  • PEGASYS

    • Drug: Ribavirin (R)
    1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
    Other Names:
  • COPEGUS

    		•
    Experimental: TMC435 100 mg 48 Wks + PR48

    Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

    Drug: TMC435
    One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

    Drug: Placebo
    One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

    Drug: Peg-IFN-alfa-2a (P)
    180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
    Other Names:
  • PEGASYS

    • Drug: Ribavirin (R)
    1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
    Other Names:
  • COPEGUS

    		•
    Experimental: TMC435 150 mg 12 Wks + PR48

    Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks.

    Drug: TMC435
    One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

    Drug: Placebo
    One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

    Drug: Peg-IFN-alfa-2a (P)
    180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
    Other Names:
  • PEGASYS

    • Drug: Ribavirin (R)
    1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
    Other Names:
  • COPEGUS

    		•
    Experimental: TMC435 150 mg 24 Wks + PR48

    Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks.

    Drug: TMC435
    One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

    Drug: Placebo
    One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

    Drug: Peg-IFN-alfa-2a (P)
    180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
    Other Names:
  • PEGASYS

    • Drug: Ribavirin (R)
    1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
    Other Names:
  • COPEGUS

    		•
    Experimental: TMC435 150 mg 48 Wks + PR48

    Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

    Drug: TMC435
    One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

    Drug: Peg-IFN-alfa-2a (P)
    180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
    Other Names:
  • PEGASYS

    • Drug: Ribavirin (R)
    1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
    Other Names:
  • COPEGUS

    		•
    Placebo Comparator: Placebo 48 Wks + PR48

    Participants will receive Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

    Drug: TMC435
    One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

    Drug: Peg-IFN-alfa-2a (P)
    180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
    Other Names:
  • PEGASYS

    • Drug: Ribavirin (R)
    1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
    Other Names:
  • COPEGUS

    		•

    Outcome Measures

    Primary Outcome Measures

    1. The Percentage of Participants Achieving a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24) [Week 72]

      The table below shows the percentage of participants in the overall population with an SVR24, defined as having plasma levels of Hepatitis C Virus ribonucleic acid less than 25 IU/mL undetectable at the EOT and 24 weeks after the EOT.

    Secondary Outcome Measures

    1. The Percentage of Participants With a Greater Than 2 log10 Drop in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Time Points During Treatment [Weeks, 2, 4, 8, and 12]

      The table below shows the percentage of participants in each treatment group who achieved a greater than 2 log10 drop in plasma levels of HCV RNA at selected time points during treatment.

    2. The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable During Treatment and Follow-up [Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72 and EOT (up to Week 48)]

      The table below shows the percentage of participants in each treatment who achieved plasma HCV RNA levels of <25 IU/mL undetectable at selected time points during treatment and follow-up and at the end of treatment (EOT).

    3. The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Detectable or Undetectable During Treatment and Follow-up [Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)]

      The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels below the limit of quantification defined as less than 25 IU/mL (detectable or undetectable) at selected time points during treatment, follow-up, and at the end of treatment (EOT).

    4. The Percentage of Participants Achieving a Rapid Virologic Response (RVR) [Week 4]

      The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having an undetectable plasma Hepatitis C virus ribonucleic acid level after receiving 4 weeks of treatment.

    5. The Percentage of Participants Achieving an Early Virologic Response (EVR) [Week 12]

      The table below shows the percentage of participants who achieved an EVR, defined as having a greater than or equal to 2 log10 reduction in plasma Hepatitis C virus ribonucleic acid from baseline at Week 12.

    6. The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) [Week 12]

      The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma levels of Hepatitis C virus ribonucleic acid at Week 12.

    7. The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) [Week 60]

      The table below shows the percentage of participants in the overall population who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the planned EOT.

    8. The Percentage of Participants With Viral Breakthrough [EOT (up to Week 48)]

      The table below shows the percentage of participants in the overall population in each treatment group during the treatment period who experienced viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in Hepatitis C virus (HCV) ribonucleic acid (RNA) from the lowest level reached or a confirmed HCV RNA of > 100 IU/mL in participants whose HCV RNA had previously been below the lower limit of quantification (i.e., less than 25 IU/mL detectable or undetectable).

    9. The Percentage of Participants With Viral Relapse [Up to Week 72]

      The table below shows the percentage of participants in the overall population who had viral relapse, defined as confirmed detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with HCV RNA less than 25 IU/mL undetectable at end of treatment.

    10. The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT) [EOT (up to Week 48)]

      The table below shows the number of participants with abnormal ALT levels at Baseline who achieved the normal ALT levels at the EOT (up to Week 48).

    11. Plasma Concentrations of TMC435 [0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48]

      The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for TMC435 for participants in each of the 6 TMC435 treatment groups.

    12. Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435 [0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48]

      The table below shows the median (range) AUC24h values for TMC435 for participants in each TMC435 treatment group.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Must have chronic hepatitis C infection as evidenced by liver biopsy, anti-hepatitis C virus (HCV) and HCV RNA positive

    • Must have chronic hepatitis C infection (genotype 1) with HCV RNA level greater than10000 IU/mL

    • Patient must have failed at least 1 prior course of peg interferon (Peg-IFN-alfa-2a)/ribavirin (RBV) therapy (standard treatment)

    • Must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication

    Exclusion Criteria:

    • Has an evidence of decompensated liver disease

    • Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)

    • Has a medical condition which is a contraindication to Peg-INF or RBV therapy

    • Have had history of, or any current medical condition which could impact the safety of the patient in the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 La Jolla California United States
    2 Los Angeles California United States
    3 Jacksonville Florida United States
    4 Miami Florida United States
    5 Orlando Florida United States
    6 Palm Harbor Florida United States
    7 Chicago Illinois United States
    8 New Orleans Louisiana United States
    9 Laurel Maryland United States
    10 Jackson Mississippi United States
    11 Tupelo Mississippi United States
    12 New York New York United States
    13 Chapel Hill North Carolina United States
    14 Cincinnati Ohio United States
    15 Germantown Tennessee United States
    16 Nashville Tennessee United States
    17 San Antonio Texas United States
    18 Concord Australia
    19 Darlinghurst Australia
    20 Fitzroy Australia
    21 Melbourne Australia
    22 New Lambton Heights Australia
    23 Parkville Australia
    24 Sydney Australia
    25 Woolloongabba N/A Australia
    26 Wien Austria
    27 Brugge Belgium
    28 Brussels Belgium
    29 Bruxelles Belgium
    30 Edegem Belgium
    31 Gent Belgium
    32 Leuven Belgium
    33 Roeselare Belgium
    34 Calgary Alberta Canada
    35 Ottawa Ontario Canada
    36 Toronto Ontario Canada
    37 Montreal Quebec Canada
    38 Creteil N/A France
    39 Grenoble France
    40 Lyon France
    41 Nice France
    42 Paris Cedex 12 France
    43 Paris France
    44 Vandoeuvre Les Nancy France
    45 Berlin Germany
    46 Düsseldorf Germany
    47 Frankfurt A. M. Germany
    48 Freiburg Germany
    49 Hannover Germany
    50 Köln Germany
    51 Stuttgart Germany
    52 Würzburg Germany
    53 Haifa Israel
    54 Jerusalem Israel
    55 Nazareth Israel
    56 Petah Tiqva Israel
    57 Ramat-Gan Israel
    58 Tel-Aviv Israel
    59 Zefat Israel
    60 Auckland New Zealand
    61 Christchurch New Zealand
    62 Hamilton New Zealand
    63 Nordbyhagen Norway
    64 Oslo Norway
    65 Tromsø Norway
    66 Bialystok Poland
    67 Bydgoszcz Poland
    68 Czeladz Poland
    69 Kielce Poland
    70 Warszawa Poland
    71 Coimbra Portugal
    72 Lisboa Portugal
    73 Porto Portugal
    74 Moscow Russian Federation
    75 Nizhny Novgorod Russian Federation
    76 Saint-Petersburg Russian Federation
    77 Samara Russian Federation
    78 Smolensk Russian Federation
    79 St Petersburg Russian Federation
    80 London United Kingdom
    81 Plymouth United Kingdom

    Sponsors and Collaborators

    • Tibotec Pharmaceuticals, Ireland

    Investigators

    • Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial, Tibotec Pharmaceuticals, Ireland

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Tibotec Pharmaceuticals, Ireland
    ClinicalTrials.gov Identifier:
    NCT00980330
    Other Study ID Numbers:
    • CR016063
    • TMC435-TiDP16-C206
    • 2009-010590-20
    First Posted:
    Sep 21, 2009
    Last Update Posted:
    Jun 9, 2014
    Last Verified:
    May 1, 2014
    Keywords provided by Tibotec Pharmaceuticals, Ireland
    Hepatitis C
    Peginterferon alpha-2a
    PegIFNalpha-2a
    RBV
    Ribavirin
    Placebo
    TMC435-TIDP16-C206
    TMC435-C206
    TMC435
    HCV
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis C
    Hepatitis
    Ribavirin
    Peginterferon alfa-2a
    Interferon alpha-2
    Simeprevir

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 89 sites in 14 countries.
    Pre-assignment Detail A total of 618 participants were screened. Of these, 463 participants were randomized of whom 462 participants started treatment. One participant in the placebo group was 'randomized in error,' did not receive treatment, and was withdrawn from the study due to non-compliance (did not come for visit).
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Period Title: Overall Study
    STARTED 66 65 66 66 68 65 66
    COMPLETED 61 60 58 61 63 61 59
    NOT COMPLETED 5 5 8 5 5 4 7

    Baseline Characteristics

    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48 Total
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Total of all reporting groups
    Overall Participants 66 65 66 66 68 65 66 462
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    51.5
    50
    50
    48
    51.5
    50
    50.5
    50
    Sex: Female, Male (Count of Participants)
    Female
    22
    33.3%
    21
    32.3%
    21
    31.8%
    21
    31.8%
    25
    36.8%
    17
    26.2%
    24
    36.4%
    151
    32.7%
    Male
    44
    66.7%
    44
    67.7%
    45
    68.2%
    45
    68.2%
    43
    63.2%
    48
    73.8%
    42
    63.6%
    311
    67.3%
    Region of Enrollment (participants) [Number]
    Asia Pacific
    4
    6.1%
    5
    7.7%
    4
    6.1%
    4
    6.1%
    1
    1.5%
    4
    6.2%
    7
    10.6%
    29
    6.3%
    Europe and Israel
    34
    51.5%
    46
    70.8%
    46
    69.7%
    49
    74.2%
    49
    72.1%
    43
    66.2%
    46
    69.7%
    313
    67.7%
    North-America
    28
    42.4%
    14
    21.5%
    16
    24.2%
    13
    19.7%
    18
    26.5%
    18
    27.7%
    13
    19.7%
    120
    26%
    Prior PR response (participants) [Number]
    Null responder
    16
    24.2%
    16
    24.6%
    18
    27.3%
    17
    25.8%
    17
    25%
    17
    26.2%
    16
    24.2%
    117
    25.3%
    Partial responder
    23
    34.8%
    23
    35.4%
    22
    33.3%
    23
    34.8%
    24
    35.3%
    22
    33.8%
    23
    34.8%
    160
    34.6%
    Relapser
    27
    40.9%
    26
    40%
    26
    39.4%
    26
    39.4%
    27
    39.7%
    26
    40%
    27
    40.9%
    185
    40%
    Metavir Score (participants) [Number]
    Not reported
    1
    1.5%
    2
    3.1%
    0
    0%
    0
    0%
    1
    1.5%
    1
    1.5%
    2
    3%
    7
    1.5%
    Score F0
    6
    9.1%
    3
    4.6%
    6
    9.1%
    5
    7.6%
    11
    16.2%
    1
    1.5%
    7
    10.6%
    39
    8.4%
    Score F1
    17
    25.8%
    14
    21.5%
    23
    34.8%
    19
    28.8%
    11
    16.2%
    27
    41.5%
    18
    27.3%
    129
    27.9%
    Score F2
    21
    31.8%
    17
    26.2%
    9
    13.6%
    18
    27.3%
    21
    30.9%
    16
    24.6%
    16
    24.2%
    118
    25.5%
    Score F3
    14
    21.2%
    16
    24.6%
    14
    21.2%
    11
    16.7%
    11
    16.2%
    7
    10.8%
    13
    19.7%
    86
    18.6%
    Score F4
    7
    10.6%
    13
    20%
    14
    21.2%
    13
    19.7%
    13
    19.1%
    13
    20%
    10
    15.2%
    83
    18%

    Outcome Measures

    1. Primary Outcome
    Title The Percentage of Participants Achieving a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24)
    Description The table below shows the percentage of participants in the overall population with an SVR24, defined as having plasma levels of Hepatitis C Virus ribonucleic acid less than 25 IU/mL undetectable at the EOT and 24 weeks after the EOT.
    Time Frame Week 72

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Number [Percentage of participants]
    69.7
    105.6%
    66.2
    101.8%
    60.6
    91.8%
    66.7
    101.1%
    72.1
    106%
    80.0
    123.1%
    22.7
    34.4%
    2. Secondary Outcome
    Title The Percentage of Participants With a Greater Than 2 log10 Drop in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Time Points During Treatment
    Description The table below shows the percentage of participants in each treatment group who achieved a greater than 2 log10 drop in plasma levels of HCV RNA at selected time points during treatment.
    Time Frame Weeks, 2, 4, 8, and 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Week 2
    97.0
    147%
    93.8
    144.3%
    97.0
    147%
    100.0
    151.5%
    95.6
    140.6%
    96.9
    149.1%
    24.2
    36.7%
    Week 4
    92.4
    140%
    93.8
    144.3%
    92.4
    140%
    97.0
    147%
    91.2
    134.1%
    96.9
    149.1%
    36.4
    55.2%
    Week 8
    92.4
    140%
    89.2
    137.2%
    89.4
    135.5%
    93.9
    142.3%
    91.2
    134.1%
    95.4
    146.8%
    57.6
    87.3%
    Week 12
    90.9
    137.7%
    87.7
    134.9%
    84.8
    128.5%
    92.4
    140%
    91.2
    134.1%
    92.3
    142%
    60.6
    91.8%
    3. Secondary Outcome
    Title The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable During Treatment and Follow-up
    Description The table below shows the percentage of participants in each treatment who achieved plasma HCV RNA levels of <25 IU/mL undetectable at selected time points during treatment and follow-up and at the end of treatment (EOT).
    Time Frame Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72 and EOT (up to Week 48)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Week 2
    22.7
    34.4%
    18.5
    28.5%
    15.2
    23%
    24.2
    36.7%
    32.4
    47.6%
    27.7
    42.6%
    0.0
    0%
    Week 4
    66.7
    101.1%
    58.5
    90%
    53.0
    80.3%
    62.1
    94.1%
    67.6
    99.4%
    66.2
    101.8%
    1.5
    2.3%
    Week 8
    77.3
    117.1%
    75.4
    116%
    77.3
    117.1%
    84.8
    128.5%
    83.8
    123.2%
    83.1
    127.8%
    7.6
    11.5%
    Week 12
    81.8
    123.9%
    73.8
    113.5%
    72.7
    110.2%
    80.3
    121.7%
    85.3
    125.4%
    83.1
    127.8%
    19.7
    29.8%
    Week 24
    81.8
    123.9%
    75.4
    116%
    78.8
    119.4%
    83.3
    126.2%
    86.8
    127.6%
    86.2
    132.6%
    42.4
    64.2%
    Week 36
    78.8
    119.4%
    73.8
    113.5%
    78.8
    119.4%
    80.3
    121.7%
    83.8
    123.2%
    81.5
    125.4%
    39.4
    59.7%
    Week 48
    81.8
    123.9%
    73.8
    113.5%
    74.2
    112.4%
    75.8
    114.8%
    80.9
    119%
    81.5
    125.4%
    37.9
    57.4%
    Week 60
    69.7
    105.6%
    67.7
    104.2%
    59.1
    89.5%
    66.7
    101.1%
    72.1
    106%
    76.9
    118.3%
    22.7
    34.4%
    Week 72
    69.7
    105.6%
    66.2
    101.8%
    60.6
    91.8%
    66.7
    101.1%
    73.5
    108.1%
    80.0
    123.1%
    22.7
    34.4%
    EOT (up to Week 48)
    80.3
    121.7%
    78.5
    120.8%
    80.3
    121.7%
    80.3
    121.7%
    83.8
    123.2%
    86.2
    132.6%
    40.9
    62%
    4. Secondary Outcome
    Title The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Detectable or Undetectable During Treatment and Follow-up
    Description The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels below the limit of quantification defined as less than 25 IU/mL (detectable or undetectable) at selected time points during treatment, follow-up, and at the end of treatment (EOT).
    Time Frame Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Week 2
    60.6
    91.8%
    55.4
    85.2%
    54.5
    82.6%
    63.6
    96.4%
    60.3
    88.7%
    66.2
    101.8%
    3.0
    4.5%
    Week 4
    78.8
    119.4%
    72.3
    111.2%
    81.8
    123.9%
    86.4
    130.9%
    82.4
    121.2%
    86.2
    132.6%
    3.0
    4.5%
    Week 8
    87.9
    133.2%
    81.5
    125.4%
    84.8
    128.5%
    87.9
    133.2%
    89.7
    131.9%
    87.7
    134.9%
    12.1
    18.3%
    Week 12
    87.9
    133.2%
    81.5
    125.4%
    83.3
    126.2%
    89.4
    135.5%
    88.2
    129.7%
    89.2
    137.2%
    34.8
    52.7%
    Week 24
    84.8
    128.5%
    78.5
    120.8%
    80.3
    121.7%
    86.4
    130.9%
    86.8
    127.6%
    89.2
    137.2%
    50.0
    75.8%
    Week 36
    81.8
    123.9%
    73.8
    113.5%
    78.8
    119.4%
    81.8
    123.9%
    86.8
    127.6%
    84.6
    130.2%
    43.9
    66.5%
    Week 48
    83.3
    126.2%
    73.8
    113.5%
    74.2
    112.4%
    78.8
    119.4%
    82.4
    121.2%
    81.5
    125.4%
    40.9
    62%
    Week 60
    71.2
    107.9%
    67.7
    104.2%
    60.6
    91.8%
    66.7
    101.1%
    72.1
    106%
    78.5
    120.8%
    22.7
    34.4%
    Week 72
    69.7
    105.6%
    66.2
    101.8%
    60.6
    91.8%
    66.7
    101.1%
    73.5
    108.1%
    80.0
    123.1%
    22.7
    34.4%
    EOT (up to Week 48)
    86.4
    130.9%
    81.5
    125.4%
    81.8
    123.9%
    89.4
    135.5%
    89.7
    131.9%
    89.2
    137.2%
    47.0
    71.2%
    5. Secondary Outcome
    Title The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
    Description The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having an undetectable plasma Hepatitis C virus ribonucleic acid level after receiving 4 weeks of treatment.
    Time Frame Week 4

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Number [Percentage of participants]
    66.7
    101.1%
    58.5
    90%
    53.0
    80.3%
    62.1
    94.1%
    67.6
    99.4%
    66.2
    101.8%
    1.5
    2.3%
    6. Secondary Outcome
    Title The Percentage of Participants Achieving an Early Virologic Response (EVR)
    Description The table below shows the percentage of participants who achieved an EVR, defined as having a greater than or equal to 2 log10 reduction in plasma Hepatitis C virus ribonucleic acid from baseline at Week 12.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Number [Percentage of participants]
    90.9
    137.7%
    87.7
    134.9%
    84.8
    128.5%
    92.4
    140%
    91.2
    134.1%
    92.3
    142%
    60.6
    91.8%
    7. Secondary Outcome
    Title The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
    Description The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma levels of Hepatitis C virus ribonucleic acid at Week 12.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Number [Percentage of participants]
    81.8
    123.9%
    73.8
    113.5%
    72.7
    110.2%
    80.3
    121.7%
    85.3
    125.4%
    83.1
    127.8%
    19.7
    29.8%
    8. Secondary Outcome
    Title The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
    Description The table below shows the percentage of participants in the overall population who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the planned EOT.
    Time Frame Week 60

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Number [Percentage of participants]
    69.7
    105.6%
    67.7
    104.2%
    60.6
    91.8%
    66.7
    101.1%
    72.1
    106%
    80.0
    123.1%
    22.7
    34.4%
    9. Secondary Outcome
    Title The Percentage of Participants With Viral Breakthrough
    Description The table below shows the percentage of participants in the overall population in each treatment group during the treatment period who experienced viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in Hepatitis C virus (HCV) ribonucleic acid (RNA) from the lowest level reached or a confirmed HCV RNA of > 100 IU/mL in participants whose HCV RNA had previously been below the lower limit of quantification (i.e., less than 25 IU/mL detectable or undetectable).
    Time Frame EOT (up to Week 48)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Number [Percentage of participants]
    10.6
    16.1%
    13.8
    21.2%
    13.6
    20.6%
    9.1
    13.8%
    10.3
    15.1%
    7.7
    11.8%
    1.5
    2.3%
    10. Secondary Outcome
    Title The Percentage of Participants With Viral Relapse
    Description The table below shows the percentage of participants in the overall population who had viral relapse, defined as confirmed detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with HCV RNA less than 25 IU/mL undetectable at end of treatment.
    Time Frame Up to Week 72

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 66 66 68 65 66
    Number [Percentage of participants]
    9.3
    14.1%
    13.7
    21.1%
    18.0
    27.3%
    11.8
    17.9%
    14.0
    20.6%
    5.5
    8.5%
    44.4
    67.3%
    11. Secondary Outcome
    Title The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT)
    Description The table below shows the number of participants with abnormal ALT levels at Baseline who achieved the normal ALT levels at the EOT (up to Week 48).
    Time Frame EOT (up to Week 48)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat: Participants who received at least 1 dose of study medication were included.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 All TMC435
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants in all 6 TMC435 treatment groups combined.
    Measure Participants 36 49 45 40 43 43 256
    Number [Percentage of participants]
    26
    39.4%
    37
    56.9%
    31
    47%
    23
    34.8%
    31
    45.6%
    33
    50.8%
    181
    274.2%
    12. Secondary Outcome
    Title Plasma Concentrations of TMC435
    Description The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for TMC435 for participants in each of the 6 TMC435 treatment groups.
    Time Frame 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication with at least 1 post-baseline pharmacokinetic (PK) assessment were included in the PK analysis population.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 65 66 68 64
    C0h
    380.5
    411.3
    529.8
    1323.5
    1074.0
    886.1
    Css,av
    691.1
    770.5
    892.0
    1960.9
    1792.3
    1606.9
    13. Secondary Outcome
    Title Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
    Description The table below shows the median (range) AUC24h values for TMC435 for participants in each TMC435 treatment group.
    Time Frame 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study medication with at least 1 post-baseline pharmacokinetic (PK) assessment were included in the PK analysis population.
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    Measure Participants 66 65 65 66 68 64
    Median (Full Range) [ng.h/mL]
    16587.0
    18492.5
    21409.0
    47061.8
    43015.0
    38564.5

    Adverse Events

    Time Frame Week 72
    Adverse Event Reporting Description
    Arm/Group Title TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Arm/Group Description Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Participants received TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Participants received TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Participants received Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
    All Cause Mortality
    TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    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 3/66 (4.5%) 5/65 (7.7%) 3/66 (4.5%) 7/66 (10.6%) 5/68 (7.4%) 8/65 (12.3%) 4/66 (6.1%)
    Blood and lymphatic system disorders
    Anaemia 1/66 (1.5%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Haemorrhagic anaemia 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Neutropenia 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Pancytopenia 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Gastrointestinal disorders
    Vomiting 0/66 (0%) 1/65 (1.5%) 0/66 (0%) 0/66 (0%) 1/68 (1.5%) 0/65 (0%) 1/66 (1.5%)
    Abdominal pain 0/66 (0%) 1/65 (1.5%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Diarrhoea 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 1/68 (1.5%) 0/65 (0%) 0/66 (0%)
    Enteritis 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 1/68 (1.5%) 0/65 (0%) 0/66 (0%)
    Gastrointestinal pain 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Periodontal disease 0/66 (0%) 0/65 (0%) 1/66 (1.5%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Haemorrhoids 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 1/66 (1.5%)
    Nausea 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 1/66 (1.5%)
    General disorders
    Non-cardiac chest pain 0/66 (0%) 1/65 (1.5%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Pyrexia 0/66 (0%) 1/65 (1.5%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Hepatobiliary disorders
    Cholecystitis 1/66 (1.5%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Infections and infestations
    Urinary tract infection 0/66 (0%) 2/65 (3.1%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Cellulitis 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 1/68 (1.5%) 1/65 (1.5%) 0/66 (0%)
    Clostridium difficile colitis 0/66 (0%) 1/65 (1.5%) 1/66 (1.5%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Gingival infection 0/66 (0%) 0/65 (0%) 1/66 (1.5%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Lung infection 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Meningitis bacterial 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Pneumonia 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 1/68 (1.5%) 0/65 (0%) 0/66 (0%)
    Pneumonia bordetella 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 1/68 (1.5%) 0/65 (0%) 0/66 (0%)
    Salpingitis 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Sinusitis 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 1/68 (1.5%) 0/65 (0%) 0/66 (0%)
    Lower respiratory tract infection 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 1/66 (1.5%)
    Tuberculosis 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 1/66 (1.5%)
    Injury, poisoning and procedural complications
    Overdose 1/66 (1.5%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Thermal burn 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Investigations
    Weight decreased 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 1/66 (1.5%)
    Metabolism and nutrition disorders
    Dehydration 0/66 (0%) 1/65 (1.5%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Diabetes mellitus 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 1/68 (1.5%) 0/65 (0%) 0/66 (0%)
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cervix carcinoma 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Hepatic neoplasm malignant 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Neurilemmoma benign 0/66 (0%) 1/65 (1.5%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Rectal cancer 1/66 (1.5%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Histiocytosis haematophagic 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 1/66 (1.5%)
    Nervous system disorders
    Brain injury 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Cerebral haemorrhage 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Coma 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Headache 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Migraine 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Viith nerve paralysis 0/66 (0%) 1/65 (1.5%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Sciatica 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 1/66 (1.5%)
    Psychiatric disorders
    Alcohol abuse 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Suicide attempt 1/66 (1.5%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Renal and urinary disorders
    Nephrolithiasis 0/66 (0%) 1/65 (1.5%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Reproductive system and breast disorders
    Metrorrhagia 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Pelvic adhesions 0/66 (0%) 0/65 (0%) 0/66 (0%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Pulmonary embolism 0/66 (0%) 0/65 (0%) 1/66 (1.5%) 0/66 (0%) 0/68 (0%) 0/65 (0%) 0/66 (0%)
    Skin and subcutaneous tissue disorders
    Drug eruption 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 1/68 (1.5%) 0/65 (0%) 0/66 (0%)
    Vascular disorders
    Hypertension 0/66 (0%) 0/65 (0%) 0/66 (0%) 0/66 (0%) 0/68 (0%) 1/65 (1.5%) 0/66 (0%)
    Other (Not Including Serious) Adverse Events
    TMC435 100mg 12 Wks + PR48 TMC435 100mg 24 Wks + PR48 TMC435 100mg 48 Wks + PR48 TMC435 150mg 12 Wks + PR48 TMC435 150mg 24 Wks + PR48 TMC435 150mg 48 Wks + PR48 Placebo 48Wks + PR48
    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 63/66 (95.5%) 61/65 (93.8%) 65/66 (98.5%) 63/66 (95.5%) 65/68 (95.6%) 63/65 (96.9%) 63/66 (95.5%)
    Blood and lymphatic system disorders
    Neutropenia 16/66 (24.2%) 15/65 (23.1%) 15/66 (22.7%) 17/66 (25.8%) 18/68 (26.5%) 20/65 (30.8%) 11/66 (16.7%)
    Anaemia 14/66 (21.2%) 11/65 (16.9%) 12/66 (18.2%) 10/66 (15.2%) 16/68 (23.5%) 13/65 (20%) 13/66 (19.7%)
    Thrombocytopenia 2/66 (3%) 2/65 (3.1%) 1/66 (1.5%) 7/66 (10.6%) 6/68 (8.8%) 5/65 (7.7%) 3/66 (4.5%)
    Leukopenia 0/66 (0%) 1/65 (1.5%) 1/66 (1.5%) 4/66 (6.1%) 3/68 (4.4%) 4/65 (6.2%) 2/66 (3%)
    Ear and labyrinth disorders
    Vertigo 2/66 (3%) 4/65 (6.2%) 4/66 (6.1%) 0/66 (0%) 3/68 (4.4%) 1/65 (1.5%) 4/66 (6.1%)
    Endocrine disorders
    Hypothyroidism 1/66 (1.5%) 1/65 (1.5%) 2/66 (3%) 0/66 (0%) 4/68 (5.9%) 1/65 (1.5%) 1/66 (1.5%)
    Eye disorders
    Dry eye 1/66 (1.5%) 4/65 (6.2%) 4/66 (6.1%) 0/66 (0%) 3/68 (4.4%) 2/65 (3.1%) 1/66 (1.5%)
    Gastrointestinal disorders
    Nausea 17/66 (25.8%) 10/65 (15.4%) 20/66 (30.3%) 20/66 (30.3%) 11/68 (16.2%) 17/65 (26.2%) 14/66 (21.2%)
    Diarrhoea 9/66 (13.6%) 11/65 (16.9%) 13/66 (19.7%) 9/66 (13.6%) 8/68 (11.8%) 9/65 (13.8%) 13/66 (19.7%)
    Dry mouth 6/66 (9.1%) 4/65 (6.2%) 4/66 (6.1%) 3/66 (4.5%) 4/68 (5.9%) 2/65 (3.1%) 2/66 (3%)
    Abdominal pain 3/66 (4.5%) 4/65 (6.2%) 1/66 (1.5%) 2/66 (3%) 6/68 (8.8%) 5/65 (7.7%) 3/66 (4.5%)
    Vomiting 3/66 (4.5%) 2/65 (3.1%) 5/66 (7.6%) 6/66 (9.1%) 3/68 (4.4%) 2/65 (3.1%) 5/66 (7.6%)
    Abdominal pain upper 2/66 (3%) 2/65 (3.1%) 4/66 (6.1%) 5/66 (7.6%) 4/68 (5.9%) 0/65 (0%) 2/66 (3%)
    Dyspepsia 1/66 (1.5%) 3/65 (4.6%) 3/66 (4.5%) 1/66 (1.5%) 4/68 (5.9%) 3/65 (4.6%) 1/66 (1.5%)
    Gastrooesophageal reflux disease 2/66 (3%) 1/65 (1.5%) 2/66 (3%) 1/66 (1.5%) 3/68 (4.4%) 4/65 (6.2%) 0/66 (0%)
    Toothache 1/66 (1.5%) 4/65 (6.2%) 2/66 (3%) 2/66 (3%) 2/68 (2.9%) 2/65 (3.1%) 2/66 (3%)
    Constipation 2/66 (3%) 4/65 (6.2%) 2/66 (3%) 0/66 (0%) 0/68 (0%) 2/65 (3.1%) 0/66 (0%)
    Aphthous stomatitis 0/66 (0%) 1/65 (1.5%) 4/66 (6.1%) 0/66 (0%) 2/68 (2.9%) 0/65 (0%) 0/66 (0%)
    Abdominal distension 0/66 (0%) 1/65 (1.5%) 4/66 (6.1%) 1/66 (1.5%) 0/68 (0%) 0/65 (0%) 1/66 (1.5%)
    General disorders
    Fatigue 30/66 (45.5%) 28/65 (43.1%) 34/66 (51.5%) 26/66 (39.4%) 28/68 (41.2%) 28/65 (43.1%) 29/66 (43.9%)
    Influenza like illness 23/66 (34.8%) 24/65 (36.9%) 21/66 (31.8%) 16/66 (24.2%) 18/68 (26.5%) 14/65 (21.5%) 13/66 (19.7%)
    Asthenia 6/66 (9.1%) 16/65 (24.6%) 11/66 (16.7%) 16/66 (24.2%) 16/68 (23.5%) 19/65 (29.2%) 7/66 (10.6%)
    Pyrexia 6/66 (9.1%) 10/65 (15.4%) 13/66 (19.7%) 14/66 (21.2%) 17/68 (25%) 9/65 (13.8%) 9/66 (13.6%)
    Irritability 9/66 (13.6%) 8/65 (12.3%) 10/66 (15.2%) 8/66 (12.1%) 10/68 (14.7%) 8/65 (12.3%) 7/66 (10.6%)
    Chills 7/66 (10.6%) 4/65 (6.2%) 4/66 (6.1%) 6/66 (9.1%) 6/68 (8.8%) 7/65 (10.8%) 6/66 (9.1%)
    Injection site erythema 3/66 (4.5%) 4/65 (6.2%) 1/66 (1.5%) 3/66 (4.5%) 3/68 (4.4%) 7/65 (10.8%) 2/66 (3%)
    Injection site reaction 3/66 (4.5%) 2/65 (3.1%) 4/66 (6.1%) 2/66 (3%) 3/68 (4.4%) 1/65 (1.5%) 0/66 (0%)
    Pain 1/66 (1.5%) 2/65 (3.1%) 1/66 (1.5%) 4/66 (6.1%) 2/68 (2.9%) 3/65 (4.6%) 4/66 (6.1%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 3/66 (4.5%) 1/65 (1.5%) 2/66 (3%) 2/66 (3%) 7/68 (10.3%) 3/65 (4.6%) 1/66 (1.5%)
    Infections and infestations
    Nasopharyngitis 1/66 (1.5%) 7/65 (10.8%) 1/66 (1.5%) 2/66 (3%) 4/68 (5.9%) 3/65 (4.6%) 0/66 (0%)
    Urinary tract infection 1/66 (1.5%) 3/65 (4.6%) 3/66 (4.5%) 3/66 (4.5%) 4/68 (5.9%) 1/65 (1.5%) 5/66 (7.6%)
    Sinusitis 7/66 (10.6%) 0/65 (0%) 3/66 (4.5%) 1/66 (1.5%) 3/68 (4.4%) 0/65 (0%) 3/66 (4.5%)
    Upper respiratory tract infection 4/66 (6.1%) 1/65 (1.5%) 0/66 (0%) 2/66 (3%) 0/68 (0%) 3/65 (4.6%) 2/66 (3%)
    Injury, poisoning and procedural complications
    Sunburn 1/66 (1.5%) 0/65 (0%) 2/66 (3%) 2/66 (3%) 0/68 (0%) 5/65 (7.7%) 0/66 (0%)
    Investigations
    Weight decreased 4/66 (6.1%) 3/65 (4.6%) 3/66 (4.5%) 5/66 (7.6%) 3/68 (4.4%) 7/65 (10.8%) 3/66 (4.5%)
    Neutrophil count decreased 2/66 (3%) 5/65 (7.7%) 0/66 (0%) 2/66 (3%) 1/68 (1.5%) 2/65 (3.1%) 2/66 (3%)
    Alanine aminotransferase increased 2/66 (3%) 2/65 (3.1%) 1/66 (1.5%) 1/66 (1.5%) 0/68 (0%) 4/65 (6.2%) 1/66 (1.5%)
    Gamma-glutamyltransferase increased 0/66 (0%) 1/65 (1.5%) 0/66 (0%) 3/66 (4.5%) 4/68 (5.9%) 0/65 (0%) 1/66 (1.5%)
    Metabolism and nutrition disorders
    Decreased appetite 11/66 (16.7%) 11/65 (16.9%) 11/66 (16.7%) 13/66 (19.7%) 13/68 (19.1%) 10/65 (15.4%) 9/66 (13.6%)
    Musculoskeletal and connective tissue disorders
    Myalgia 16/66 (24.2%) 4/65 (6.2%) 6/66 (9.1%) 11/66 (16.7%) 11/68 (16.2%) 16/65 (24.6%) 12/66 (18.2%)
    Arthralgia 7/66 (10.6%) 5/65 (7.7%) 9/66 (13.6%) 15/66 (22.7%) 7/68 (10.3%) 7/65 (10.8%) 9/66 (13.6%)
    Back pain 2/66 (3%) 2/65 (3.1%) 2/66 (3%) 3/66 (4.5%) 9/68 (13.2%) 2/65 (3.1%) 8/66 (12.1%)
    Muscle spasms 4/66 (6.1%) 3/65 (4.6%) 1/66 (1.5%) 3/66 (4.5%) 4/68 (5.9%) 1/65 (1.5%) 4/66 (6.1%)
    Nervous system disorders
    Headache 18/66 (27.3%) 19/65 (29.2%) 23/66 (34.8%) 29/66 (43.9%) 26/68 (38.2%) 23/65 (35.4%) 24/66 (36.4%)
    Dizziness 1/66 (1.5%) 4/65 (6.2%) 7/66 (10.6%) 6/66 (9.1%) 4/68 (5.9%) 7/65 (10.8%) 6/66 (9.1%)
    Disturbance in attention 3/66 (4.5%) 8/65 (12.3%) 5/66 (7.6%) 1/66 (1.5%) 3/68 (4.4%) 5/65 (7.7%) 3/66 (4.5%)
    Dysgeusia 5/66 (7.6%) 2/65 (3.1%) 6/66 (9.1%) 6/66 (9.1%) 1/68 (1.5%) 2/65 (3.1%) 3/66 (4.5%)
    Psychiatric disorders
    Insomnia 11/66 (16.7%) 11/65 (16.9%) 16/66 (24.2%) 11/66 (16.7%) 20/68 (29.4%) 10/65 (15.4%) 9/66 (13.6%)
    Depression 7/66 (10.6%) 8/65 (12.3%) 8/66 (12.1%) 10/66 (15.2%) 6/68 (8.8%) 6/65 (9.2%) 6/66 (9.1%)
    Sleep disorder 5/66 (7.6%) 2/65 (3.1%) 5/66 (7.6%) 7/66 (10.6%) 2/68 (2.9%) 5/65 (7.7%) 2/66 (3%)
    Anxiety 5/66 (7.6%) 2/65 (3.1%) 3/66 (4.5%) 2/66 (3%) 2/68 (2.9%) 3/65 (4.6%) 3/66 (4.5%)
    Depressed mood 2/66 (3%) 2/65 (3.1%) 3/66 (4.5%) 0/66 (0%) 2/68 (2.9%) 5/65 (7.7%) 3/66 (4.5%)
    Mood altered 2/66 (3%) 0/65 (0%) 3/66 (4.5%) 4/66 (6.1%) 0/68 (0%) 1/65 (1.5%) 2/66 (3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 10/66 (15.2%) 18/65 (27.7%) 13/66 (19.7%) 11/66 (16.7%) 8/68 (11.8%) 16/65 (24.6%) 8/66 (12.1%)
    Dyspnoea 10/66 (15.2%) 9/65 (13.8%) 8/66 (12.1%) 4/66 (6.1%) 8/68 (11.8%) 10/65 (15.4%) 4/66 (6.1%)
    Dyspnoea exertional 4/66 (6.1%) 4/65 (6.2%) 4/66 (6.1%) 2/66 (3%) 3/68 (4.4%) 3/65 (4.6%) 3/66 (4.5%)
    Epistaxis 1/66 (1.5%) 3/65 (4.6%) 3/66 (4.5%) 4/66 (6.1%) 2/68 (2.9%) 1/65 (1.5%) 4/66 (6.1%)
    Nasal dryness 0/66 (0%) 0/65 (0%) 4/66 (6.1%) 1/66 (1.5%) 1/68 (1.5%) 2/65 (3.1%) 1/66 (1.5%)
    Oropharyngeal pain 2/66 (3%) 1/65 (1.5%) 0/66 (0%) 0/66 (0%) 3/68 (4.4%) 1/65 (1.5%) 5/66 (7.6%)
    Skin and subcutaneous tissue disorders
    Pruritus 19/66 (28.8%) 26/65 (40%) 21/66 (31.8%) 20/66 (30.3%) 25/68 (36.8%) 24/65 (36.9%) 11/66 (16.7%)
    Dry skin 9/66 (13.6%) 15/65 (23.1%) 12/66 (18.2%) 14/66 (21.2%) 10/68 (14.7%) 12/65 (18.5%) 10/66 (15.2%)
    Rash 8/66 (12.1%) 8/65 (12.3%) 6/66 (9.1%) 10/66 (15.2%) 13/68 (19.1%) 16/65 (24.6%) 9/66 (13.6%)
    Alopecia 5/66 (7.6%) 3/65 (4.6%) 7/66 (10.6%) 7/66 (10.6%) 6/68 (8.8%) 7/65 (10.8%) 5/66 (7.6%)
    Erythema 4/66 (6.1%) 5/65 (7.7%) 7/66 (10.6%) 3/66 (4.5%) 5/68 (7.4%) 2/65 (3.1%) 2/66 (3%)
    Eczema 3/66 (4.5%) 3/65 (4.6%) 5/66 (7.6%) 3/66 (4.5%) 0/68 (0%) 1/65 (1.5%) 2/66 (3%)
    Photosensitivity reaction 0/66 (0%) 1/65 (1.5%) 2/66 (3%) 1/66 (1.5%) 3/68 (4.4%) 7/65 (10.8%) 1/66 (1.5%)
    Night sweats 1/66 (1.5%) 1/65 (1.5%) 5/66 (7.6%) 1/66 (1.5%) 1/68 (1.5%) 1/65 (1.5%) 3/66 (4.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Global Clinical Development Manager
    Organization Jan-Cil France
    Phone
    Email ClinicalTrialDisclosure@its.jnj.com
    Responsible Party:
    Tibotec Pharmaceuticals, Ireland
    ClinicalTrials.gov Identifier:
    NCT00980330
    Other Study ID Numbers:
    • CR016063
    • TMC435-TiDP16-C206
    • 2009-010590-20
    First Posted:
    Sep 21, 2009
    Last Update Posted:
    Jun 9, 2014
    Last Verified:
    May 1, 2014