Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00090233
First received: August 25, 2004
Last updated: November 10, 2014
Last verified: November 2014
Results First Received: June 29, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Condition: Rotavirus Infections
Interventions: Biological: Rotateq™
Biological: Comparator: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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 Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

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.


Reporting Groups
  Description
RotaTeq™ 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 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.

Participant Flow:   Overall Study
    RotaTeq™     Placebo  
STARTED     34644 [1]   34630 [2]
Vaccinated at Visit 1     34035 [3]   34003 [4]
Vaccinated at Visit 2     31052     31066  
Vaccinated at Visit 3     29667     29598  
COMPLETED     29645 [5]   29565 [5]
NOT COMPLETED     4999     5065  
Randomized Not Vaccinated (Visit 1)                 609                 627  
Adverse Event                 214                 198  
Lost to Follow-up                 68                 95  
Protocol Violation                 960                 1022  
Withdrawal by Subject                 182                 211  
Moved                 203                 189  
Not Specified                 1211                 1160  
Data not available at data cut-off point                 1552                 1563  
[1] Evaluated by data safety monitoring board (DSMB) when they recommended stopping enrollment
[2] Evaluated by data safety monitoring board when they recommended stopping enrollment
[3] Randomized Not vaccinated 609
[4] Randomized Not vaccinated 627
[5] Does not include participants who discontinued prior to the 42 day safety follow-up



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
RotaTeq™ 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 Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
Total Total of all reporting groups

Baseline Measures
    RotaTeq™     Placebo     Total  
Number of Participants  
[units: participants]
  34644     34630     69274  
Age, Customized [1]
[units: Participants]
     
5 Weeks of Age and Under     1     4     5  
6 to 12 Weeks of Age     34551     34527     69078  
Over 12 Weeks of Age     92     99     191  
Gender  
[units: participants]
     
Female     17058     17101     34159  
Male     17586     17529     35115  
Race/Ethnicity  
[units: participants]
     
White     23772     23788     47560  
Hispanic American     4963     4911     9874  
Black     2908     2941     5849  
Multi Racial     1815     1817     3632  
Asian     536     552     1088  
Native American     531     514     1045  
Other     119     107     226  
[1] The eligibility for this study was to enroll infants 6-12 weeks of age; however infants that were 5 weeks and under, and infants who were 12 weeks and over were inadvertently enrolled outside these ranges. Those infants who received at least 1 dose of study vaccine, were followed for safety.



  Outcome Measures
  Hide All Outcome Measures

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

Measure Type Primary
Measure Title Intussusception Within 42 Days Following Any Dose of RotaTeq™/Placebo
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants in the study were followed for potential cases of intussusception.

Reporting Groups
  Description
RotaTeq™ 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 Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
  34002     33969  
Intussusception Within 42 Days Following Any Dose of RotaTeq™/Placebo  
[units: Participants]
  6     5  


Statistical Analysis 1 for Intussusception Within 42 Days Following Any Dose of RotaTeq™/Placebo
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Exact binomial test
P Value [4] 0.006
relative risk [5] 1.6
95% Confidence Interval ( 0.4 to 6.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Relative Risk ≤10.0 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Exact binomial test adjusted for group-sequential design.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 

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.

[5] Other relevant estimation information:
  No text entered.



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

Measure Type Primary
Measure Title Occurrence of Rotavirus Disease Caused by Serotypes G1, G2, G3 and G4 That Occurs 14 Days Following the 3rd Vaccination
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Population Using Per-Protocol Case Definition

Reporting Groups
  Description
RotaTeq™ 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.
Placebo 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.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
  2207     2305  
Occurrence of Rotavirus Disease Caused by Serotypes G1, G2, G3 and G4 That Occurs 14 Days Following the 3rd Vaccination  
[units: Participants]
  82     315  


Statistical Analysis 1 for Occurrence of Rotavirus Disease Caused by Serotypes G1, G2, G3 and G4 That Occurs 14 Days Following the 3rd Vaccination
Groups [1] All groups
Method [2] Exact binomial test
P Value [3] <0.001
Efficacy=1-Relative Risk [4] 74.0
95% Confidence Interval ( 66.8 to 79.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Exact binomial test.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 

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.

[4] Other relevant estimation information:
  Efficacy = 1-RR, expressed as a percentage; the RR is the incidence in the vaccine group / the incidence in the placebo group.



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

Measure Type Secondary
Measure Title G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Population among participants in Finland using Per-Protocol Case Definition

Reporting Groups
  Description
RotaTeq™ 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.
Placebo 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.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
  117     89  
G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus  
[units: Participants]
  95     8  


Statistical Analysis 1 for G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus
Groups [1] RotaTeq™
Method [2] Exact binomial test
P Value [3] <0.001
Proportion [4] 81.2
95% Confidence Interval ( 72.9 to 87.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   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   [ Time Frame: At least 14 days following the 3rd vaccination ]

Measure Type Secondary
Measure 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
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Population Using Per-Protocol Case Definition

Reporting Groups
  Description
RotaTeq™ 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 Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
  28646     28488  
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  
[units: Annual # of events per 1000 person-years]
   
Hospital admissions     6     144  
Emergency department visits     14     213  


Statistical Analysis 1 for 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
Groups [1] All groups
Method [2] Poisson regression
P Value [3] <0.001
Risk Ratio (RR) [4] 94.5
95% Confidence Interval ( 91.2 to 96.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
 

Poisson regression with generalized estimating equations.

Validated with Van Elteren’s extension of Wilcoxon Rank Sum test.

[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Rate Reduction>0%
[4] Other relevant estimation information:
  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:   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.   [ Time Frame: At least 14 days following the 3rd vaccination through the first rotavirus season ]

Measure Type Secondary
Measure 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.
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Population Using Per-Protocol Case Definition

Reporting Groups
  Description
RotaTeq™ 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 Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
  2201     2292  
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.  
[units: Participants]
   
First episode scores     48     262  
Worst episode scores     49     265  


Statistical Analysis 1 for 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.
Groups [1] All groups
Method [2] Exact binomial test
P Value [3] <0.001
Efficacy=1-Relative Risk [4] 81.5
95% Confidence Interval ( 74.9 to 86.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.
[4] Other relevant estimation information:
  Estimated value is based on the worst episode scores.



6.  Secondary:   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   [ Time Frame: At least 14 days following the 3rd vaccination through the first rotavirus season ]

Measure Type Secondary
Measure 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
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Population Using Per-Protocol Case Definition

Reporting Groups
  Description
RotaTeq™ 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 Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
  2198     2271  
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  
[units: Participants]
   
First episode scores     1     51  
Worst episode scores     1     51  


Statistical Analysis 1 for 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
Groups [1] All groups
Method [2] Exact binomial test
P Value [3] <0.001
Efficacy=1-Relative Risk [4] 98.0
95% Confidence Interval ( 88.3 to 100 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.
[4] Other relevant estimation information:
  No text entered.



7.  Secondary:   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   [ Time Frame: 42 days following third dose ]

Measure Type Secondary
Measure 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
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Population

Reporting Groups
  Description
RotaTeq™ 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 Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
  558     592  
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  
[units: Participants]
   
Hepatitis B (N=202, N=214)     197     203  
Haemophilus influenzae type b (N=558, N=592)     417     426  
Diphtheria (N=136, N=144)     136     142  
Tetanus (N=132, N=140)     132     140  
Polio type 1 (N=341, N=360)     328     349  
Polio type 2 (N=341, N=359)     311     326  
Polio type 3 (N=341, N=359)     324     343  


Statistical Analysis 1 for 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
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Miettenen and Nurminen
P Value [4] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Difference (vaccine-placebo) in seroprotection rates was greater than -.10 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.



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

Measure Type Secondary
Measure Title Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Population; excluding protocol violators and participants with invalid data based on laboratory determinations.

Reporting Groups
  Description
RotaTeq™ 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 Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
  59     78  
Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin  
[units: ELISA units/mL]
Geometric Mean ( 95% Confidence Interval )
   
Pertussis PT     20.18  
  ( 17.10 to 23.81 )  
  22.73  
  ( 19.59 to 26.37 )  
Pertussis FHA     55.69  
  ( 48.01 to 64.59 )  
  64.33  
  ( 55.41 to 74.69 )  
Pertussis Pertactin     34.77  
  ( 26.46 to 45.70 )  
  59.17  
  ( 46.21 to 75.76 )  


Statistical Analysis 1 for Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for Pertussis PT [5] 0.9
95% Confidence Interval ( 0.7 to 1.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for Pertussis PT was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for Pertussis FHA [5] 0.9
95% Confidence Interval ( 0.7 to 1.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for Pertussis FHA was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] 0.193
GMTR for Pertussis Pertactin [5] 0.6
95% Confidence Interval ( 0.4 to 0.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for Pertussis Pertactin was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



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

Measure Type Secondary
Measure Title Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Population; excluding protocol violators and participants with invalid data based on laboratory determinations.

Reporting Groups
  Description
RotaTeq™ 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 Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
  185     198  
Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F  
[units: micrograms/mL]
Geometric Mean ( 95% Confidence Interval )
   
Pneumococcal serotype 4 (N=181, N=196)     1.13  
  ( 0.99 to 1.29 )  
  0.96  
  ( 0.84 to 1.09 )  
Pneumococcal serotype 6B (N=185, N=198)     2.39  
  ( 1.93 to 2.95 )  
  1.72  
  ( 1.38 to 2.13 )  
Pneumococcal serotype 9V (N=166, N=181)     1.90  
  ( 1.66 to 2.19 )  
  1.78  
  ( 1.55 to 2.04 )  
Pneumococcal serotype 14 (N=178, N=198)     4.24  
  ( 3.39 to 5.29 )  
  4.33  
  ( 3.55 to 5.28 )  
Pneumococcal serotype 18C (N=166, N=180)     2.60  
  ( 2.30 to 2.94 )  
  2.02  
  ( 1.76 to 2.32 )  
Pneumococcal serotype 19F (N=180, N=196)     1.97  
  ( 1.61 to 2.42 )  
  1.84  
  ( 1.55 to 2.20 )  
Pneumococcal serotype 23F (N=185, N=198)     1.71  
  ( 1.41 to 2.07 )  
  1.50  
  ( 1.24 to 1.80 )  


Statistical Analysis 1 for Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for pneumococcal serotype 4 [5] 1.2
95% Confidence Interval ( 1.0 to 1.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 4 was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for pneumococcal serotype 6B [5] 1.4
95% Confidence Interval ( 1.0 to 1.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 6B was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for pneumococcal serotype 9V [5] 1.1
95% Confidence Interval ( 0.9 to 1.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 9V was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for pneumococcal serotype 14 [5] 1.0
95% Confidence Interval ( 0.7 to 1.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 14 was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for pneumococcal serotype 18C [5] 1.3
95% Confidence Interval ( 1.1 to 1.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 18C was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 6 for Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for pneumococcal serotype 19F [5] 1.1
95% Confidence Interval ( 0.8 to 1.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 19F was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 7 for Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for pneumococcal serotype 23F [5] 1.1
95% Confidence Interval ( 0.9 to 1.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for pneumococcal serotype 23F was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
70,301 participants randomized, 69,274 evaluated, when DSMB first recommended ending enrollment.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked 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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked 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: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372


Publications of Results:
Publications automatically indexed to this study:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00090233     History of Changes
Other Study ID Numbers: V260-006, 2004_012
Study First Received: August 25, 2004
Results First Received: June 29, 2009
Last Updated: November 10, 2014
Health Authority: United States: Food and Drug Administration