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Rotavirus Efficacy and Safety Trial (REST)(V260-006)

Sponsor
Merck Sharp & Dohme Corp. (Industry)
Overall Status
Completed
CT.gov ID
NCT00090233
Collaborator
(none)
69,274
Enrollment
2
Arms
45
Duration (Months)

Study Details

Study Description

Brief Summary

This study was designed to evaluate the safety of the investigational rotavirus vaccine and the efficacy to prevent rotavirus gastroenteritis.

Condition or Disease Intervention/Treatment Phase
  • Biological: Rotateq™
  • Biological: Comparator: Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
69274 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
Safety and Efficacy of Pentavalent (G1, G2, G3, G4 , and P1) Human-Bovine Reassortant Rotavirus Vaccine in Healthy Infants
Study Start Date :
Jan 1, 2001
Actual Primary Completion Date :
Oct 1, 2004
Actual Study Completion Date :
Oct 1, 2004

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

RotaTeq

Biological: Rotateq™
3 doses of 2.0 mL RotaTeq administered orally. Dose 1 will be given at study entry, Dose 2 will be given 4-10 weeks after Dose 1, Dose 3 will be given 4-10 weeks after Dose 2.
Other Names:
  • V260

    		•
    Placebo Comparator: 2

    Placebo

    Biological: Comparator: Placebo
    3 doses of 2.0 mL Placebo to RotaTeq administered orally. Dose 1 will be given at study entry, Dose 2 will be given 4-10 weeks after Dose 1, Dose 3 will be given 4-10 weeks after Dose 2.

    Outcome Measures

    Primary Outcome Measures

    1. Intussusception Within 42 Days Following Any Dose of RotaTeq™/Placebo [Within 42 days following any dose of RotaTeq™/placebo]

      Number of participants with confirmed intussusception within 42 days after each vaccination with RotaTeq™/placebo.

    2. Occurrence of Rotavirus Disease Caused by Serotypes G1, G2, G3 and G4 That Occurs 14 Days Following the 3rd Vaccination [At least 14 days following the 3rd vaccination through the first full rotavirus season]

      Rotavirus gastroenteritis cases consist of all participants with one or more episodes classified as positive. Multiple positive episodes for one participant are counted as a single case.

    Secondary Outcome Measures

    1. G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus [14 days following the 3rd vaccination]

      Number of participants with a 3-fold rise or greater in G1 Serum neutralizing antibody (SNA) responses against rotavirus from baseline to postdose 3.

    2. Occurrence of Hospital Admissions and Visits to Emergency Departments (or the Equivalent at International Sites) for Rotavirus Disease Associated With Serotypes G1, G2, G3, or G4 [At least 14 days following the 3rd vaccination]

      Health Outcomes Substudy - Occurrence of hospital admissions and emergency department visits for episode(s) of rotavirus gastroenteritis associated with serotypes G1, G2, G3, or G4 by treatment group. Occurrence was expressed as the annual number of events per 1000 person-years.

    3. Efficacy of a 3-dose Regimen of RotaTeq™ Against Moderate-to-severe Rotavirus Disease (Clinical Score >8) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose. [At least 14 days following the 3rd vaccination through the first rotavirus season]

      Number of participants with rotavirus gastroenteritis whose clinical score was >8 for the first episode and for the worst episode. Scores evaluated the intensity and duration of diarrhea, vomiting, fever, and behavioral symptoms. The total score for an episode is equal to the sum of the scores for each of the symptoms [range: total score 0 (best) to 24 (worst)].

    4. Efficacy of a 3-dose Regimen of RotaTeq™ Against Severe Rotavirus Disease (Clinical Score > 16) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose [At least 14 days following the 3rd vaccination through the first rotavirus season]

      Number of participants with rotavirus gastroenteritis whose clinical score was >16 for the first episode and for the worst episode. Scores evaluated the intensity and duration of diarrhea, vomiting, fever, and behavioral symptoms. The total score for an episode is equal to the sum of the scores for each of the symptoms [range: total score 0 (best) to 24 (worst)].

    5. Seroprotection/Seroconversion for Hepatitis B, Haemophilus Influenzae Type b, Diphtheria, Tetanus, & Polio Types 1,2,& 3 Who Received COMVAX™, INFANRIX™, IPOL™ & PREVNAR™ Concomitantly With RotaTeq™ Versus Placebo [42 days following third dose]

      The number of participants who achieved seroprotection/seroconversion to hepatitis B, Haemophilus influenzae type b, diphtheria, tetanus, & polio types 1, 2, & 3, per established criteria.

    6. Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin [42 days following third dose]

      Measurement of immune response in the group that received RotaTeq™ and the group that received placebo was performed by determining geometric mean antibody titers to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin. Antibody titers were measured with an indirect, non-competitive, enzyme immunoassay (EIA).

    7. Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F [42 days following third dose]

      Measurement of immune response in the group that received RotaTeq™ and the group that received placebo was performed by determining geometric mean antibody titers to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Serum antibody titers to type-specific pneumococcal polysaccharides were determined by an EIA.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Weeks to 12 Weeks
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Healthy infants
    Exclusion Criteria:
    • None Specified

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme Corp.

    Investigators

    • Study Director: Medical Monitor, Merck Sharp & Dohme Corp.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme Corp.
    ClinicalTrials.gov Identifier:
    NCT00090233
    Other Study ID Numbers:
    • V260-006
    • 2004_012
    First Posted:
    Aug 27, 2004
    Last Update Posted:
    Oct 5, 2015
    Last Verified:
    Sep 1, 2015
    Additional relevant MeSH terms:
    Rotavirus Infections

    Study Results

    Participant Flow

    Recruitment Details Participants were recruited at 356 sites in Belgium, Costa Rica, Finland, Germany, Guatemala, Italy, Jamaica, Mexico, Puerto Rico, Sweden, Taiwan, and the United States from 12 Jan 2001 first patient in (FPI) to 06 Oct 2004 last patient in (LPI).
    Pre-assignment Detail Participants with: history of congenital abdominal disorders, intussusception, or abdominal surgery; history of known prior rotavirus disease, chronic diarrhea, or failure to thrive were excluded from the trial before assignment to groups.
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart with up to 42 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) through the first rotavirus season postvaccination. The rotavirus season for each site was prospectively determined using historical epidemiologic data. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart with up to 42 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) through the first rotavirus season postvaccination. The rotavirus season for each site was prospectively determined using historical epidemiologic data.
    Period Title: Overall Study
    STARTED 34644 34630
    Vaccinated at Visit 1 34035 34003
    Vaccinated at Visit 2 31052 31066
    Vaccinated at Visit 3 29667 29598
    COMPLETED 29645 29565
    NOT COMPLETED 4999 5065

    Baseline Characteristics

    Arm/Group Title RotaTeq™ Placebo Total
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. Total of all reporting groups
    Overall Participants 34644 34630 69274
    Age, Customized (Number) [Number]
    5 Weeks of Age and Under
    1
    0%
    4
    0%
    5
    0%
    6 to 12 Weeks of Age
    34551
    99.7%
    34527
    99.7%
    69078
    99.7%
    Over 12 Weeks of Age
    92
    0.3%
    99
    0.3%
    191
    0.3%
    Sex: Female, Male (Count of Participants)
    Female
    17058
    49.2%
    17101
    49.4%
    34159
    49.3%
    Male
    17586
    50.8%
    17529
    50.6%
    35115
    50.7%
    Race/Ethnicity (participants) [Number]
    White
    23772
    68.6%
    23788
    68.7%
    47560
    68.7%
    Hispanic American
    4963
    14.3%
    4911
    14.2%
    9874
    14.3%
    Black
    2908
    8.4%
    2941
    8.5%
    5849
    8.4%
    Multi Racial
    1815
    5.2%
    1817
    5.2%
    3632
    5.2%
    Asian
    536
    1.5%
    552
    1.6%
    1088
    1.6%
    Native American
    531
    1.5%
    514
    1.5%
    1045
    1.5%
    Other
    119
    0.3%
    107
    0.3%
    226
    0.3%

    Outcome Measures

    1. Primary Outcome
    Title Intussusception Within 42 Days Following Any Dose of RotaTeq™/Placebo
    Description Number of participants with confirmed intussusception within 42 days after each vaccination with RotaTeq™/placebo.
    Time Frame Within 42 days following any dose of RotaTeq™/placebo

    Outcome Measure Data

    Analysis Population Description
    All participants in the study were followed for potential cases of intussusception.
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
    Measure Participants 34002 33969
    Number [Participants]
    6
    0%
    5
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Relative Risk ≤10.0 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value 0.006
    Comments p≤ 10/11, where p is proportion of participants with intussusception in vaccine group relative to total number of participants with intussusception. Based on conditional binomial approach. Adjusted for group-sequential design.
    Method Exact binomial test
    Comments Exact binomial test adjusted for group-sequential design.
    Method of Estimation Estimation Parameter relative risk
    Estimated Value 1.6
    Confidence Interval () 95%
    0.4 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus
    Description Number of participants with a 3-fold rise or greater in G1 Serum neutralizing antibody (SNA) responses against rotavirus from baseline to postdose 3.
    Time Frame 14 days following the 3rd vaccination

    Outcome Measure Data

    Analysis Population Description
    Per Protocol Population among participants in Finland using Per-Protocol Case Definition
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Participants randomized to treatment with RotaTeq™ tested with data available for analysis excluding protocol violators, participants with invalid data based on laboratory determinations, participants with wildtype rotavirus detected in the stool, or with samples taken outside the range of 9 to 33 days postdose 3. Participants randomized to treatment with Placebo tested with data available for analysis excluding protocol violators, participants with invalid data based on laboratory determinations, participants with wildtype rotavirus detected in the stool, or with samples taken outside the range of 9 to 33 days postdose 3.
    Measure Participants 117 89
    Number [Participants]
    95
    0.3%
    8
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RotaTeq™
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments p≥42%, where p is proportion of participants with ≥3-fold rise in antibody titer from Predose 1 to Postdose 3 in vaccine group. Based on binomial approach.
    Method Exact binomial test
    Comments
    Method of Estimation Estimation Parameter Proportion
    Estimated Value 81.2
    Confidence Interval () 95%
    72.9 to 87.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    Title Occurrence of Rotavirus Disease Caused by Serotypes G1, G2, G3 and G4 That Occurs 14 Days Following the 3rd Vaccination
    Description Rotavirus gastroenteritis cases consist of all participants with one or more episodes classified as positive. Multiple positive episodes for one participant are counted as a single case.
    Time Frame At least 14 days following the 3rd vaccination through the first full rotavirus season

    Outcome Measure Data

    Analysis Population Description
    Per Protocol Population Using Per-Protocol Case Definition
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description The number of participants randomized to treatment with RotaTeq™ is different from the number analyzed because some participants were excluded due to protocol violations and/or participants without follow-up and/or participants classified as unevaluable due to detection of wildtype rotavirus in the stool prior to 14 days Postdose 3; incomplete clinical and/or laboratory results; or stool samples collected out of day range. The number of participants randomized to treatment with Placebo is different from the number analyzed because some participants were excluded due to protocol violations and/or participants without follow-up and/or participants classified as unevaluable due to detection of wildtype rotavirus in the stool prior to 14 days Postdose 3; incomplete clinical and/or laboratory results; or stool samples collected out of day range.
    Measure Participants 2207 2305
    Number [Participants]
    82
    0.2%
    315
    0.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Efficacy≥35%. Based on p≤.65/(.65+k), where p is proportion of participants with outcome in vaccine group relative to total number of participants with outcome, k is ratio of follow-up time; placebo/vaccine. Based on conditional binomial approach.
    Method Exact binomial test
    Comments Exact binomial test.
    Method of Estimation Estimation Parameter Efficacy=1-Relative Risk
    Estimated Value 74.0
    Confidence Interval () 95%
    66.8 to 79.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Efficacy = 1-RR, expressed as a percentage; the RR is the incidence in the vaccine group / the incidence in the placebo group.
    4. Secondary Outcome
    Title Occurrence of Hospital Admissions and Visits to Emergency Departments (or the Equivalent at International Sites) for Rotavirus Disease Associated With Serotypes G1, G2, G3, or G4
    Description Health Outcomes Substudy - Occurrence of hospital admissions and emergency department visits for episode(s) of rotavirus gastroenteritis associated with serotypes G1, G2, G3, or G4 by treatment group. Occurrence was expressed as the annual number of events per 1000 person-years.
    Time Frame At least 14 days following the 3rd vaccination

    Outcome Measure Data

    Analysis Population Description
    Per Protocol Population Using Per-Protocol Case Definition
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
    Measure Participants 28646 28488
    Hospital admissions
    6
    144
    Emergency department visits
    14
    213
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Rate Reduction>0%
    Method Poisson regression
    Comments Poisson regression with generalized estimating equations. Validated with Van Elteren's extension of Wilcoxon Rank Sum test.
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 94.5
    Confidence Interval () 95%
    91.2 to 96.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Risk ratio of rate of hospitalizations and emergency department visits between treatment groups. Reported here are results after 12 additional emergency department visits were identified among placebo recipients and data were re-analyzed.
    5. Secondary Outcome
    Title Efficacy of a 3-dose Regimen of RotaTeq™ Against Moderate-to-severe Rotavirus Disease (Clinical Score >8) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose.
    Description Number of participants with rotavirus gastroenteritis whose clinical score was >8 for the first episode and for the worst episode. Scores evaluated the intensity and duration of diarrhea, vomiting, fever, and behavioral symptoms. The total score for an episode is equal to the sum of the scores for each of the symptoms [range: total score 0 (best) to 24 (worst)].
    Time Frame At least 14 days following the 3rd vaccination through the first rotavirus season

    Outcome Measure Data

    Analysis Population Description
    Per Protocol Population Using Per-Protocol Case Definition
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
    Measure Participants 2201 2292
    First episode scores
    48
    0.1%
    262
    0.8%
    Worst episode scores
    49
    0.1%
    265
    0.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Efficacy>0%. Based on p< 1/(1+k), where p is proportion of participants with outcome in vaccine group relative to total number of participants with outcome, and k is ratio of follow-up time; placebo / vaccine. Based on conditional binomial approach.
    Method Exact binomial test
    Comments
    Method of Estimation Estimation Parameter Efficacy=1-Relative Risk
    Estimated Value 81.5
    Confidence Interval () 95%
    74.9 to 86.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimated value is based on the worst episode scores.
    6. Secondary Outcome
    Title Efficacy of a 3-dose Regimen of RotaTeq™ Against Severe Rotavirus Disease (Clinical Score > 16) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose
    Description Number of participants with rotavirus gastroenteritis whose clinical score was >16 for the first episode and for the worst episode. Scores evaluated the intensity and duration of diarrhea, vomiting, fever, and behavioral symptoms. The total score for an episode is equal to the sum of the scores for each of the symptoms [range: total score 0 (best) to 24 (worst)].
    Time Frame At least 14 days following the 3rd vaccination through the first rotavirus season

    Outcome Measure Data

    Analysis Population Description
    Per Protocol Population Using Per-Protocol Case Definition
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
    Measure Participants 2198 2271
    First episode scores
    1
    0%
    51
    0.1%
    Worst episode scores
    1
    0%
    51
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Efficacy>0%. Based on p< 1/(1+k), where p is proportion of participants with outcome in vaccine group relative to total number of participants with outcome, and k is ratio of follow-up time; placebo/vaccine. Based on conditional binomial approach.
    Method Exact binomial test
    Comments
    Method of Estimation Estimation Parameter Efficacy=1-Relative Risk
    Estimated Value 98.0
    Confidence Interval () 95%
    88.3 to 100
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Seroprotection/Seroconversion for Hepatitis B, Haemophilus Influenzae Type b, Diphtheria, Tetanus, & Polio Types 1,2,& 3 Who Received COMVAX™, INFANRIX™, IPOL™ & PREVNAR™ Concomitantly With RotaTeq™ Versus Placebo
    Description The number of participants who achieved seroprotection/seroconversion to hepatitis B, Haemophilus influenzae type b, diphtheria, tetanus, & polio types 1, 2, & 3, per established criteria.
    Time Frame 42 days following third dose

    Outcome Measure Data

    Analysis Population Description
    Per Protocol Population
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
    Measure Participants 558 592
    Hepatitis B (N=202, N=214)
    197
    0.6%
    203
    0.6%
    Haemophilus influenzae type b (N=558, N=592)
    417
    1.2%
    426
    1.2%
    Diphtheria (N=136, N=144)
    136
    0.4%
    142
    0.4%
    Tetanus (N=132, N=140)
    132
    0.4%
    140
    0.4%
    Polio type 1 (N=341, N=360)
    328
    0.9%
    349
    1%
    Polio type 2 (N=341, N=359)
    311
    0.9%
    326
    0.9%
    Polio type 3 (N=341, N=359)
    324
    0.9%
    343
    1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Difference (vaccine-placebo) in seroprotection rates was greater than -.10 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments p<0.001 was obtained for all comparisons. pv - pp ≥-.10, where p is proportion of participants who achieved seroprotection in the vaccine and placebo groups, respectively.
    Method Miettenen and Nurminen
    Comments
    8. Secondary Outcome
    Title Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin
    Description Measurement of immune response in the group that received RotaTeq™ and the group that received placebo was performed by determining geometric mean antibody titers to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin. Antibody titers were measured with an indirect, non-competitive, enzyme immunoassay (EIA).
    Time Frame 42 days following third dose

    Outcome Measure Data

    Analysis Population Description
    Per Protocol Population; excluding protocol violators and participants with invalid data based on laboratory determinations.
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
    Measure Participants 59 78
    Pertussis PT
    20.18
    22.73
    Pertussis FHA
    55.69
    64.33
    Pertussis Pertactin
    34.77
    59.17
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for Pertussis PT was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for Pertussis PT
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    0.7 to 1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for Pertussis FHA was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for Pertussis FHA
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    0.7 to 1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for Pertussis Pertactin was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value 0.193
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for Pertussis Pertactin
    Estimated Value 0.6
    Confidence Interval (2-Sided) 95%
    0.4 to 0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F
    Description Measurement of immune response in the group that received RotaTeq™ and the group that received placebo was performed by determining geometric mean antibody titers to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Serum antibody titers to type-specific pneumococcal polysaccharides were determined by an EIA.
    Time Frame 42 days following third dose

    Outcome Measure Data

    Analysis Population Description
    Per Protocol Population; excluding protocol violators and participants with invalid data based on laboratory determinations.
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
    Measure Participants 185 198
    Pneumococcal serotype 4 (N=181, N=196)
    1.13
    0.96
    Pneumococcal serotype 6B (N=185, N=198)
    2.39
    1.72
    Pneumococcal serotype 9V (N=166, N=181)
    1.90
    1.78
    Pneumococcal serotype 14 (N=178, N=198)
    4.24
    4.33
    Pneumococcal serotype 18C (N=166, N=180)
    2.60
    2.02
    Pneumococcal serotype 19F (N=180, N=196)
    1.97
    1.84
    Pneumococcal serotype 23F (N=185, N=198)
    1.71
    1.50
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 4 was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for pneumococcal serotype 4
    Estimated Value 1.2
    Confidence Interval () 95%
    1.0 to 1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 6B was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for pneumococcal serotype 6B
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    1.0 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 9V was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for pneumococcal serotype 9V
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    0.9 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 14 was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for pneumococcal serotype 14
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    0.7 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 18C was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for pneumococcal serotype 18C
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    1.1 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 19F was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for pneumococcal serotype 19F
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    0.8 to 1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection RotaTeq™, Placebo
    Comments The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 23F was used for analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments GMTR was greater than 0.5 (non-inferiority margin).
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 1 sided
    Comments t-test on natural log of titers
    Method of Estimation Estimation Parameter GMTR for pneumococcal serotype 23F
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    0.9 to 1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Participants in this study were followed for all serious adverse events (SAEs) and other adverse events (AEs), for up to 42 days following each study vaccination
    Adverse Event Reporting Description Participants listed in SAE tables (34904-RotaTeq; 34862-Placebo) are those who received study treatment. Other AEs were reported for a pre-defined subset who received ≥1 dose (4808-RotaTeq; 4796-Placebo). Although a participant may have had ≥ 2 AEs they are counted only once in a category. The same participant may appear in different categories.
    Arm/Group Title RotaTeq™ Placebo
    Arm/Group Description Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. The Not Completed total includes participants discontinued at any time before the completion of the third study vaccination and/or the 42-day safety follow-up period post vaccination 3. Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart. The Not Completed total includes participants discontinued at any time before the completion of the third study vaccination and/or the 42-day safety follow-up period post vaccination 3.
    All Cause Mortality
    RotaTeq™ Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    RotaTeq™ Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 863/34904 (2.5%) 955/34862 (2.7%)
    Blood and lymphatic system disorders
    Anaemia 7/34904 (0%) 3/34862 (0%)
    Idiopathic thrombocytopenic purpura 1/34904 (0%) 0/34862 (0%)
    Lymphadenitis 2/34904 (0%) 4/34862 (0%)
    Lymphadenopathy 0/34904 (0%) 2/34862 (0%)
    Neutropenia 0/34904 (0%) 2/34862 (0%)
    Thrombocytopenia 1/34904 (0%) 0/34862 (0%)
    Cardiac disorders
    Bradycardia 1/34904 (0%) 0/34862 (0%)
    Cardiac failure congestive 2/34904 (0%) 1/34862 (0%)
    Cardio-respiratory arrest 1/34904 (0%) 0/34862 (0%)
    Cardiopulmonary failure 0/34904 (0%) 1/34862 (0%)
    Cyanosis 3/34904 (0%) 1/34862 (0%)
    Congenital, familial and genetic disorders
    Atrial septal defect 1/34904 (0%) 1/34862 (0%)
    Cerebral palsy 0/34904 (0%) 1/34862 (0%)
    Coarctation of the aorta 0/34904 (0%) 2/34862 (0%)
    Congenital cystic kidney disease 0/34904 (0%) 1/34862 (0%)
    Congenital intestinal malformation 1/34904 (0%) 1/34862 (0%)
    Cryptorchism 0/34904 (0%) 1/34862 (0%)
    Cystic fibrosis 1/34904 (0%) 1/34862 (0%)
    Developmental glaucoma 0/34904 (0%) 1/34862 (0%)
    Glycogen storage disease type ib 1/34904 (0%) 0/34862 (0%)
    Hip dysplasia 2/34904 (0%) 0/34862 (0%)
    Hydrocele 1/34904 (0%) 0/34862 (0%)
    Kidney malformation 1/34904 (0%) 0/34862 (0%)
    Polycystic liver disease 0/34904 (0%) 1/34862 (0%)
    Pulmonary artery stenosis congenital 1/34904 (0%) 0/34862 (0%)
    Pyloric stenosis 1/34904 (0%) 2/34862 (0%)
    Retinoblastoma 0/34904 (0%) 1/34862 (0%)
    Ventricular septal defect 1/34904 (0%) 2/34862 (0%)
    Eye disorders
    Chalazion 1/34904 (0%) 0/34862 (0%)
    Conjunctivitis 0/34904 (0%) 1/34862 (0%)
    Gastrointestinal disorders
    Abdominal distension 2/34904 (0%) 3/34862 (0%)
    Abdominal pain 5/34904 (0%) 3/34862 (0%)
    Anal fissure 3/34904 (0%) 1/34862 (0%)
    Anal fistula 0/34904 (0%) 2/34862 (0%)
    Anal haemorrhage 1/34904 (0%) 0/34862 (0%)
    Anal skin tags 1/34904 (0%) 0/34862 (0%)
    Aphthous stomatitis 0/34904 (0%) 1/34862 (0%)
    Cheilitis 1/34904 (0%) 0/34862 (0%)
    Colitis 1/34904 (0%) 0/34862 (0%)
    Constipation 7/34904 (0%) 6/34862 (0%)
    Diarrhoea 9/34904 (0%) 21/34862 (0.1%)
    Diarrhoea haemorrhagic 1/34904 (0%) 0/34862 (0%)
    Duodenitis 1/34904 (0%) 0/34862 (0%)
    Dysphagia 1/34904 (0%) 0/34862 (0%)
    Enteritis 2/34904 (0%) 4/34862 (0%)
    Faecaloma 1/34904 (0%) 0/34862 (0%)
    Flatulence 0/34904 (0%) 2/34862 (0%)
    Gastric ulcer 1/34904 (0%) 0/34862 (0%)
    Gastritis 0/34904 (0%) 1/34862 (0%)
    Gastrointestinal inflammation 0/34904 (0%) 1/34862 (0%)
    Gastrointestinal pain 0/34904 (0%) 1/34862 (0%)
    Gastrooesophageal reflux disease 29/34904 (0.1%) 17/34862 (0%)
    Haematemesis 3/34904 (0%) 0/34862 (0%)
    Haematochezia 1/34904 (0%) 3/34862 (0%)
    Infantile colic 2/34904 (0%) 2/34862 (0%)
    Inguinal hernia 11/34904 (0%) 8/34862 (0%)
    Inguinal hernia, obstructive 1/34904 (0%) 1/34862 (0%)
    Intussusception 13/34904 (0%) 22/34862 (0.1%)
    Nausea 0/34904 (0%) 1/34862 (0%)
    Oesophageal obstruction 1/34904 (0%) 0/34862 (0%)
    Oesophagitis 0/34904 (0%) 1/34862 (0%)
    Rectal prolapse 0/34904 (0%) 1/34862 (0%)
    Reflux oesophagitis 1/34904 (0%) 1/34862 (0%)
    Regurgitation of food 1/34904 (0%) 2/34862 (0%)
    Retching 0/34904 (0%) 1/34862 (0%)
    Stomatitis 0/34904 (0%) 2/34862 (0%)
    Umbilical hernia 1/34904 (0%) 0/34862 (0%)
    Varices oesophageal 1/34904 (0%) 0/34862 (0%)
    Volvulus of bowel 0/34904 (0%) 1/34862 (0%)
    Vomiting 23/34904 (0.1%) 20/34862 (0.1%)
    General disorders
    Brain death 0/34904 (0%) 1/34862 (0%)
    Chills 0/34904 (0%) 1/34862 (0%)
    Cyst 0/34904 (0%) 1/34862 (0%)
    Death 1/34904 (0%) 4/34862 (0%)
    Drowning 0/34904 (0%) 1/34862 (0%)
    Fever neonatal 2/34904 (0%) 1/34862 (0%)
    Hernia 1/34904 (0%) 0/34862 (0%)
    Injection site inflammation 1/34904 (0%) 0/34862 (0%)
    Irritability 9/34904 (0%) 4/34862 (0%)
    Near sudden infant death syndrome 1/34904 (0%) 1/34862 (0%)
    Oedema peripheral 2/34904 (0%) 0/34862 (0%)
    Pyrexia 43/34904 (0.1%) 49/34862 (0.1%)
    Sudden death 1/34904 (0%) 0/34862 (0%)
    Sudden infant death syndrome 7/34904 (0%) 9/34862 (0%)
    Hepatobiliary disorders
    Hepatic steatosis 1/34904 (0%) 0/34862 (0%)
    Hepatomegaly 1/34904 (0%) 0/34862 (0%)
    Immune system disorders
    Anaphylactic reaction 0/34904 (0%) 1/34862 (0%)
    Food allergy 1/34904 (0%) 0/34862 (0%)
    Hypersensitivity 1/34904 (0%) 1/34862 (0%)
    Milk allergy 4/34904 (0%) 1/34862 (0%)
    Infections and infestations
    Abscess 0/34904 (0%) 1/34862 (0%)
    Abscess neck 1/34904 (0%) 1/34862 (0%)
    Acute tonsillitis 0/34904 (0%) 1/34862 (0%)
    Adenovirus infection 1/34904 (0%) 0/34862 (0%)
    Amoebic dysentery 0/34904 (0%) 1/34862 (0%)
    Anal abscess 2/34904 (0%) 0/34862 (0%)
    Arthritis bacterial 0/34904 (0%) 1/34862 (0%)
    Bacteraemia 1/34904 (0%) 1/34862 (0%)
    Botulism 2/34904 (0%) 0/34862 (0%)
    Bronchiolitis 215/34904 (0.6%) 253/34862 (0.7%)
    Bronchitis 25/34904 (0.1%) 20/34862 (0.1%)
    Bronchitis acute 3/34904 (0%) 3/34862 (0%)
    Bronchitis acute viral 0/34904 (0%) 1/34862 (0%)
    Bronchitis chronic 1/34904 (0%) 2/34862 (0%)
    Bronchitis viral 1/34904 (0%) 1/34862 (0%)
    Bronchopneumonia 11/34904 (0%) 6/34862 (0%)
    Campylobacter intestinal infection 1/34904 (0%) 0/34862 (0%)
    Catheter site infection 0/34904 (0%) 1/34862 (0%)
    Cellulitis 1/34904 (0%) 6/34862 (0%)
    Cellulitis staphylococcal 1/34904 (0%) 0/34862 (0%)
    Chest wall abscess 1/34904 (0%) 0/34862 (0%)
    Clostridium colitis 0/34904 (0%) 1/34862 (0%)
    Coxsackie viral infection 0/34904 (0%) 1/34862 (0%)
    Croup infectious 8/34904 (0%) 5/34862 (0%)
    Cystitis 2/34904 (0%) 0/34862 (0%)
    Dysentery 1/34904 (0%) 0/34862 (0%)
    Ear infection 3/34904 (0%) 2/34862 (0%)
    Eczema infected 0/34904 (0%) 1/34862 (0%)
    Enterocolitis infectious 0/34904 (0%) 1/34862 (0%)
    Enterovirus infection 0/34904 (0%) 1/34862 (0%)
    Escherichia sepsis 0/34904 (0%) 1/34862 (0%)
    Escherichia urinary tract infection 0/34904 (0%) 2/34862 (0%)
    Exanthema subitum 3/34904 (0%) 2/34862 (0%)
    Febrile infection 2/34904 (0%) 3/34862 (0%)
    Gastroenteritis 73/34904 (0.2%) 127/34862 (0.4%)
    Gastroenteritis adenovirus 4/34904 (0%) 1/34862 (0%)
    Gastroenteritis rotavirus 3/34904 (0%) 18/34862 (0.1%)
    Gastroenteritis salmonella 2/34904 (0%) 4/34862 (0%)
    Gastroenteritis viral 8/34904 (0%) 6/34862 (0%)
    Gastrointestinal infection 0/34904 (0%) 1/34862 (0%)
    Groin abscess 0/34904 (0%) 1/34862 (0%)
    Haemophilus sepsis 0/34904 (0%) 1/34862 (0%)
    Herpes simplex 1/34904 (0%) 0/34862 (0%)
    Impetigo 1/34904 (0%) 0/34862 (0%)
    Influenza 5/34904 (0%) 6/34862 (0%)
    Kawasaki's disease 5/34904 (0%) 0/34862 (0%)
    Laryngitis 12/34904 (0%) 6/34862 (0%)
    Laryngotracheitis 2/34904 (0%) 0/34862 (0%)
    Laryngotracheo bronchitis 0/34904 (0%) 1/34862 (0%)
    Lobar pneumonia 7/34904 (0%) 4/34862 (0%)
    Lower respiratory tract infection 0/34904 (0%) 3/34862 (0%)
    Meningitis 4/34904 (0%) 2/34862 (0%)
    Meningitis aseptic 2/34904 (0%) 2/34862 (0%)
    Meningitis bacterial 1/34904 (0%) 1/34862 (0%)
    Meningitis enteroviral 0/34904 (0%) 1/34862 (0%)
    Meningitis haemophilus 0/34904 (0%) 1/34862 (0%)
    Meningitis streptococcal 2/34904 (0%) 0/34862 (0%)
    Meningitis viral 3/34904 (0%) 4/34862 (0%)
    Nasopharyngitis 0/34904 (0%) 1/34862 (0%)
    Oral candidiasis 4/34904 (0%) 1/34862 (0%)
    Otitis externa 2/34904 (0%) 0/34862 (0%)
    Otitis media 28/34904 (0.1%) 24/34862 (0.1%)
    Otitis media acute 3/34904 (0%) 2/34862 (0%)
    Parainfluenzae virus infection 2/34904 (0%) 0/34862 (0%)
    Parotitis 1/34904 (0%) 0/34862 (0%)
    Perianal abscess 2/34904 (0%) 0/34862 (0%)
    Perineal abscess 0/34904 (0%) 1/34862 (0%)
    Periorbital cellulitis 2/34904 (0%) 2/34862 (0%)
    Pertussis 6/34904 (0%) 7/34862 (0%)
    Pharyngitis 2/34904 (0%) 3/34862 (0%)
    Pneumococcal bacteraemia 1/34904 (0%) 0/34862 (0%)
    Pneumococcal infection 0/34904 (0%) 1/34862 (0%)
    Pneumococcal sepsis 0/34904 (0%) 1/34862 (0%)
    Pneumocystis jiroveci pneumonia 0/34904 (0%) 1/34862 (0%)
    Pneumonia 55/34904 (0.2%) 58/34862 (0.2%)
    Pneumonia bacterial 0/34904 (0%) 1/34862 (0%)
    Pneumonia primary atypical 1/34904 (0%) 1/34862 (0%)
    Pneumonia respiratory syncytial viral 5/34904 (0%) 2/34862 (0%)
    Pneumonia viral 1/34904 (0%) 3/34862 (0%)
    Pseudocroup 0/34904 (0%) 2/34862 (0%)
    Pyelocystitis 1/34904 (0%) 0/34862 (0%)
    Pyelonephritis 22/34904 (0.1%) 27/34862 (0.1%)
    Pyelonephritis acute 16/34904 (0%) 12/34862 (0%)
    Respiratory syncytial virus infection 10/34904 (0%) 6/34862 (0%)
    Respiratory tract infection 13/34904 (0%) 14/34862 (0%)
    Respiratory tract infection viral 3/34904 (0%) 2/34862 (0%)
    Rhinitis 1/34904 (0%) 1/34862 (0%)
    Roseola 2/34904 (0%) 1/34862 (0%)
    Salmonellosis 0/34904 (0%) 2/34862 (0%)
    Scrotal infection 0/34904 (0%) 1/34862 (0%)
    Sepsis 7/34904 (0%) 4/34862 (0%)
    Septic shock 1/34904 (0%) 2/34862 (0%)
    Sinusitis 1/34904 (0%) 0/34862 (0%)
    Skin infection 0/34904 (0%) 2/34862 (0%)
    Staphylococcal sepsis 1/34904 (0%) 0/34862 (0%)
    Subcutaneous abscess 1/34904 (0%) 0/34862 (0%)
    Tonsillitis 0/34904 (0%) 1/34862 (0%)
    Tonsillitis streptococcal 0/34904 (0%) 1/34862 (0%)
    Tuberculosis 2/34904 (0%) 0/34862 (0%)
    Tuberculosis of peripheral lymph nodes 1/34904 (0%) 0/34862 (0%)
    Upper respiratory tract infection 27/34904 (0.1%) 15/34862 (0%)
    Urinary tract infection 38/34904 (0.1%) 29/34862 (0.1%)
    Urosepsis 0/34904 (0%) 6/34862 (0%)
    Varicella 2/34904 (0%) 0/34862 (0%)
    Viral infection 14/34904 (0%) 17/34862 (0%)
    Viral pharyngitis 0/34904 (0%) 1/34862 (0%)
    Viral rash 1/34904 (0%) 0/34862 (0%)
    Viral upper respiratory tract infection 2/34904 (0%) 4/34862 (0%)
    Injury, poisoning and procedural complications
    Accidental overdose 1/34904 (0%) 0/34862 (0%)
    Burns second degree 1/34904 (0%) 1/34862 (0%)
    Concussion 3/34904 (0%) 6/34862 (0%)
    Contusion 2/34904 (0%) 1/34862 (0%)
    Extradural haematoma 0/34904 (0%) 1/34862 (0%)
    Fall 3/34904 (0%) 5/34862 (0%)
    Femur fracture 1/34904 (0%) 5/34862 (0%)
    Fractured skull depressed 1/34904 (0%) 1/34862 (0%)
    Head injury 3/34904 (0%) 2/34862 (0%)
    Heat exhaustion 0/34904 (0%) 1/34862 (0%)
    Humerus fracture 0/34904 (0%) 2/34862 (0%)
    Injury asphyxiation 2/34904 (0%) 0/34862 (0%)
    Limb injury 1/34904 (0%) 0/34862 (0%)
    Multiple fractures 2/34904 (0%) 0/34862 (0%)
    Overdose 3/34904 (0%) 2/34862 (0%)
    Post procedural haematoma 0/34904 (0%) 1/34862 (0%)
    Road traffic accident 4/34904 (0%) 2/34862 (0%)
    Skull fracture 7/34904 (0%) 7/34862 (0%)
    Subdural haematoma 0/34904 (0%) 1/34862 (0%)
    Subdural haemorrhage 1/34904 (0%) 0/34862 (0%)
    Thermal burn 1/34904 (0%) 4/34862 (0%)
    Tibia fracture 0/34904 (0%) 1/34862 (0%)
    Upper limb fracture 0/34904 (0%) 1/34862 (0%)
    Investigations
    Body temperature increased 1/34904 (0%) 0/34862 (0%)
    Occult blood positive 6/34904 (0%) 3/34862 (0%)
    Transaminases increased 1/34904 (0%) 0/34862 (0%)
    Weight decreased 0/34904 (0%) 2/34862 (0%)
    Metabolism and nutrition disorders
    Acidosis 1/34904 (0%) 1/34862 (0%)
    Anorexia 3/34904 (0%) 4/34862 (0%)
    Cow's milk intolerance 0/34904 (0%) 1/34862 (0%)
    Decreased appetite 3/34904 (0%) 1/34862 (0%)
    Dehydration 19/34904 (0.1%) 23/34862 (0.1%)
    Diet refusal 5/34904 (0%) 4/34862 (0%)
    Failure to thrive 2/34904 (0%) 4/34862 (0%)
    Feeding disorder 2/34904 (0%) 0/34862 (0%)
    Feeding disorder neonatal 0/34904 (0%) 1/34862 (0%)
    Food intolerance 0/34904 (0%) 2/34862 (0%)
    Hyperinsulinaemia 1/34904 (0%) 0/34862 (0%)
    Hypernatraemia 0/34904 (0%) 1/34862 (0%)
    Hyponatraemia 1/34904 (0%) 0/34862 (0%)
    Lactose intolerance 1/34904 (0%) 0/34862 (0%)
    Metabolic acidosis 0/34904 (0%) 2/34862 (0%)
    Weight gain poor 1/34904 (0%) 2/34862 (0%)
    Musculoskeletal and connective tissue disorders
    Chondromalacia 1/34904 (0%) 0/34862 (0%)
    Growth retardation 0/34904 (0%) 1/34862 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Brain neoplasm 1/34904 (0%) 1/34862 (0%)
    Haemangioma 4/34904 (0%) 2/34862 (0%)
    Neoplasm malignant 1/34904 (0%) 2/34862 (0%)
    Neuroblastoma 0/34904 (0%) 3/34862 (0%)
    Pineal parenchymal neoplasm malignant 1/34904 (0%) 0/34862 (0%)
    Nervous system disorders
    Anoxic encephalopathy 0/34904 (0%) 1/34862 (0%)
    Brain oedema 2/34904 (0%) 0/34862 (0%)
    Cerebral haemorrhage 1/34904 (0%) 0/34862 (0%)
    Convulsion 17/34904 (0%) 9/34862 (0%)
    Depressed level of consciousness 0/34904 (0%) 1/34862 (0%)
    Encephalopathy 1/34904 (0%) 0/34862 (0%)
    Epilepsy 4/34904 (0%) 2/34862 (0%)
    Febrile convulsion 6/34904 (0%) 4/34862 (0%)
    Hemiplegia 1/34904 (0%) 0/34862 (0%)
    Hydrocephalus 1/34904 (0%) 2/34862 (0%)
    Hypotonia 1/34904 (0%) 0/34862 (0%)
    Hypoxic encephalopathy 1/34904 (0%) 1/34862 (0%)
    Infantile spasms 1/34904 (0%) 3/34862 (0%)
    Intraneural cyst 1/34904 (0%) 0/34862 (0%)
    Lethargy 0/34904 (0%) 1/34862 (0%)
    Loss of consciousness 0/34904 (0%) 1/34862 (0%)
    Myoclonus 0/34904 (0%) 1/34862 (0%)
    Nystagmus 0/34904 (0%) 1/34862 (0%)
    Somnolence 0/34904 (0%) 3/34862 (0%)
    Spinal cord haemorrhage 1/34904 (0%) 0/34862 (0%)
    Status epilepticus 0/34904 (0%) 1/34862 (0%)
    Subarachnoid haemorrhage 1/34904 (0%) 1/34862 (0%)
    Syncope 1/34904 (0%) 0/34862 (0%)
    Syncope vasovagal 0/34904 (0%) 1/34862 (0%)
    Thalamus haemorrhage 1/34904 (0%) 0/34862 (0%)
    Tremor 0/34904 (0%) 1/34862 (0%)
    Vocal cord paralysis 1/34904 (0%) 0/34862 (0%)
    Psychiatric disorders
    Agitation 1/34904 (0%) 0/34862 (0%)
    Apathy 0/34904 (0%) 1/34862 (0%)
    Breath holding 2/34904 (0%) 0/34862 (0%)
    Crying 5/34904 (0%) 5/34862 (0%)
    Eating disorder 0/34904 (0%) 1/34862 (0%)
    Restlessness 0/34904 (0%) 1/34862 (0%)
    Sleep disorder 1/34904 (0%) 1/34862 (0%)
    Staring 0/34904 (0%) 1/34862 (0%)
    Renal and urinary disorders
    Hydronephrosis 1/34904 (0%) 1/34862 (0%)
    Vesicoureteric reflux 1/34904 (0%) 1/34862 (0%)
    Reproductive system and breast disorders
    Balanitis 1/34904 (0%) 1/34862 (0%)
    Epididymitis 1/34904 (0%) 1/34862 (0%)
    Phimosis 0/34904 (0%) 1/34862 (0%)
    Testicular torsion 1/34904 (0%) 0/34862 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 0/34904 (0%) 1/34862 (0%)
    Apnoea 7/34904 (0%) 5/34862 (0%)
    Apnoeic attack 2/34904 (0%) 3/34862 (0%)
    Aspiration 1/34904 (0%) 1/34862 (0%)
    Asthma 10/34904 (0%) 11/34862 (0%)
    Atelectasis 1/34904 (0%) 1/34862 (0%)
    Bronchial hyperactivity 7/34904 (0%) 5/34862 (0%)
    Bronchospasm 3/34904 (0%) 0/34862 (0%)
    Choking 1/34904 (0%) 2/34862 (0%)
    Chronic respiratory disease 0/34904 (0%) 1/34862 (0%)
    Cough 3/34904 (0%) 3/34862 (0%)
    Dyspnoea 1/34904 (0%) 2/34862 (0%)
    Hypoxia 5/34904 (0%) 5/34862 (0%)
    Interstitial lung disease 0/34904 (0%) 1/34862 (0%)
    Laryngospasm 2/34904 (0%) 0/34862 (0%)
    Nasal congestion 0/34904 (0%) 1/34862 (0%)
    Neonatal apnoeic attack 1/34904 (0%) 0/34862 (0%)
    Neonatal respiratory distress syndrome 1/34904 (0%) 0/34862 (0%)
    Obstructive airways disorder 0/34904 (0%) 2/34862 (0%)
    Pulmonary congestion 0/34904 (0%) 1/34862 (0%)
    Pulmonary haemorrhage 0/34904 (0%) 1/34862 (0%)
    Respiratory acidosis 1/34904 (0%) 0/34862 (0%)
    Respiratory disorder 1/34904 (0%) 1/34862 (0%)
    Respiratory distress 7/34904 (0%) 7/34862 (0%)
    Respiratory failure 1/34904 (0%) 2/34862 (0%)
    Rhinitis allergic 1/34904 (0%) 2/34862 (0%)
    Sleep apnoea syndrome 1/34904 (0%) 1/34862 (0%)
    Status asthmaticus 1/34904 (0%) 0/34862 (0%)
    Tachypnoea 1/34904 (0%) 1/34862 (0%)
    Tracheomalacia 1/34904 (0%) 0/34862 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis 2/34904 (0%) 0/34862 (0%)
    Dermatitis allergic 1/34904 (0%) 0/34862 (0%)
    Dermatitis atopic 4/34904 (0%) 5/34862 (0%)
    Eczema 1/34904 (0%) 0/34862 (0%)
    Eczema infantile 0/34904 (0%) 1/34862 (0%)
    Lichen sclerosus 0/34904 (0%) 1/34862 (0%)
    Psoriasis 0/34904 (0%) 1/34862 (0%)
    Purpura 0/34904 (0%) 1/34862 (0%)
    Rash 1/34904 (0%) 0/34862 (0%)
    Seborrhoea 1/34904 (0%) 0/34862 (0%)
    Urticaria 2/34904 (0%) 2/34862 (0%)
    Urticaria pigmentosa 0/34904 (0%) 1/34862 (0%)
    Social circumstances
    Child abuse 1/34904 (0%) 1/34862 (0%)
    Child neglect 0/34904 (0%) 1/34862 (0%)
    Overfeeding of infant 1/34904 (0%) 0/34862 (0%)
    Vascular disorders
    Circulatory collapse 1/34904 (0%) 0/34862 (0%)
    Haematoma 0/34904 (0%) 2/34862 (0%)
    Haemorrhage 0/34904 (0%) 1/34862 (0%)
    Pallor 0/34904 (0%) 1/34862 (0%)
    Vasculitis 0/34904 (0%) 1/34862 (0%)
    Other (Not Including Serious) Adverse Events
    RotaTeq™ Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4000/4800 (83.3%) 4047/4787 (84.5%)
    Eye disorders
    Conjunctivitis 315/4800 (6.6%) 339/4787 (7.1%)
    Gastrointestinal disorders
    Abdominal pain upper 53/4800 (1.1%) 40/4787 (0.8%)
    Constipation 188/4800 (3.9%) 214/4787 (4.5%)
    Diarrhoea 1047/4800 (21.8%) 1022/4787 (21.3%)
    Flatulence 273/4800 (5.7%) 282/4787 (5.9%)
    Gastrooesophageal reflux disease 62/4800 (1.3%) 59/4787 (1.2%)
    Infantile colic 70/4800 (1.5%) 65/4787 (1.4%)
    Regurgitation of food 175/4800 (3.6%) 183/4787 (3.8%)
    Teething 196/4800 (4.1%) 165/4787 (3.4%)
    Vomiting 613/4800 (12.8%) 644/4787 (13.5%)
    General disorders
    Injection site pain 216/4800 (4.5%) 228/4787 (4.8%)
    Irritability 881/4800 (18.4%) 862/4787 (18%)
    Pyrexia 1970/4800 (41%) 2056/4787 (42.9%)
    Infections and infestations
    Bronchiolitis 200/4800 (4.2%) 185/4787 (3.9%)
    Bronchitis 79/4800 (1.6%) 73/4787 (1.5%)
    Candida nappy rash 46/4800 (1%) 51/4787 (1.1%)
    Ear infection 94/4800 (2%) 107/4787 (2.2%)
    Gastroenteritis 447/4800 (9.3%) 454/4787 (9.5%)
    Influenza 89/4800 (1.9%) 72/4787 (1.5%)
    Nasopharyngitis 276/4800 (5.8%) 277/4787 (5.8%)
    Oral candidiasis 185/4800 (3.9%) 188/4787 (3.9%)
    Otitis media 624/4800 (13%) 602/4787 (12.6%)
    Pharyngitis 60/4800 (1.3%) 57/4787 (1.2%)
    Respiratory tract infection 97/4800 (2%) 83/4787 (1.7%)
    Rhinitis 348/4800 (7.3%) 337/4787 (7%)
    Upper respiratory tract infection 1230/4800 (25.6%) 1279/4787 (26.7%)
    Viral infection 105/4800 (2.2%) 121/4787 (2.5%)
    Metabolism and nutrition disorders
    Decreased appetite 68/4800 (1.4%) 67/4787 (1.4%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 45/4800 (0.9%) 46/4787 (1%)
    Psychiatric disorders
    Agitation 215/4800 (4.5%) 180/4787 (3.8%)
    Crying 160/4800 (3.3%) 190/4787 (4%)
    Restlessness 63/4800 (1.3%) 69/4787 (1.4%)
    Respiratory, thoracic and mediastinal disorders
    Cough 471/4800 (9.8%) 456/4787 (9.5%)
    Nasal congestion 293/4800 (6.1%) 294/4787 (6.1%)
    Rhinorrhoea 222/4800 (4.6%) 254/4787 (5.3%)
    Wheezing 52/4800 (1.1%) 51/4787 (1.1%)
    Skin and subcutaneous tissue disorders
    Dermatitis 47/4800 (1%) 25/4787 (0.5%)
    Dermatitis diaper 106/4800 (2.2%) 120/4787 (2.5%)
    Eczema 129/4800 (2.7%) 110/4787 (2.3%)
    Rash 167/4800 (3.5%) 153/4787 (3.2%)

    Limitations/Caveats

    70,301 participants randomized, 69,274 evaluated, when DSMB first recommended ending enrollment.

    More Information

    Certain Agreements

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

    Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp
    Phone 1-800-672-6372
    Email
    Responsible Party:
    Merck Sharp & Dohme Corp.
    ClinicalTrials.gov Identifier:
    NCT00090233
    Other Study ID Numbers:
    • V260-006
    • 2004_012
    First Posted:
    Aug 27, 2004
    Last Update Posted:
    Oct 5, 2015
    Last Verified:
    Sep 1, 2015