Clinical Trial Results:
A phase III randomized, placebo-controlled clinical trial to study the efficacy and safety of V260 in healthy infants in Japan
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Summary
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EudraCT number |
2017-000264-15 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
26 Aug 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
06 May 2017
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First version publication date |
06 May 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
V260-029
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00718237 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Aug 2009
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Aug 2009
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of the study is to evaluate whether V260 is effective and well tolerated in healthy Japanese infants.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Aug 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Japan: 762
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Worldwide total number of subjects |
762
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
762
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Healthy Japanese infants with no known history of rotavirus gastroenteritis were enrolled in the study. | |||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 768 participants were screened and 762 were enrolled in the study. | |||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | |||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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RotaTeq™ | |||||||||||||||||||||||||||||||||
Arm description |
Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart beginning on Day 1, with 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until a total of 30 cases are confirmed (up to approximately 25 months). | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent)
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Investigational medicinal product code |
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Other name |
V260
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Three 2-mL doses of oral solution administered 28 to 70 days apart
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Arm title
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Placebo | |||||||||||||||||||||||||||||||||
Arm description |
Three doses of placebo administered 28 to 70 days apart beginning on Day 1, with 14 days of safety follow-up after each vaccination, and follow-up for AGEs until a total of 30 cases are confirmed (up to approximately 25 months). | |||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Three 2-mL doses of oral solution administered 28 to 70 days apart
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Baseline characteristics reporting groups
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Reporting group title |
RotaTeq™
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Reporting group description |
Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart beginning on Day 1, with 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until a total of 30 cases are confirmed (up to approximately 25 months). | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Three doses of placebo administered 28 to 70 days apart beginning on Day 1, with 14 days of safety follow-up after each vaccination, and follow-up for AGEs until a total of 30 cases are confirmed (up to approximately 25 months). | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
RotaTeq™
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Reporting group description |
Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart beginning on Day 1, with 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until a total of 30 cases are confirmed (up to approximately 25 months). | ||
Reporting group title |
Placebo
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Reporting group description |
Three doses of placebo administered 28 to 70 days apart beginning on Day 1, with 14 days of safety follow-up after each vaccination, and follow-up for AGEs until a total of 30 cases are confirmed (up to approximately 25 months). | ||
Subject analysis set title |
RotaTeq™ Per Protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants randomized to receive RotaTeq™ except those excluded with protocol deviations that may affect the results of the primary efficacy endpoint.
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Subject analysis set title |
Placebo Per Protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants randomized to receive placebo except those excluded with protocol deviations that may affect the results of the primary efficacy endpoint.
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End point title |
Incidence Rate of Rotavirus Gastroenteritis of Any Severity Caused by Rotavirus Serotypes G1, G2, G3, G4 and G-serotypes Associated With P1A | |||||||||
End point description |
Any severity cases of rotavirus gastroenteritis caused by G1, G2, G3, G4 or G-serotypes associated with P1A occurring at least 14 days postdose 3 in the per-protocol population using per-protocol case definition. The population analyzed was per-protocol participants except those unevaluable due to 1) detection of wild-type rotavirus in stool prior to 14 days Postdose 3, 2) incomplete clinical and/or laboratory results, or 3) stool samples collected out of day range.
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End point type |
Primary
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End point timeframe |
From 14 days Postdose 3 onward
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Statistical analysis title |
Vaccine Efficacy | |||||||||
Statistical analysis description |
Efficacy = 1-RR, expressed as a percentage; the RR is the incidence in the vaccine group / the incidence in the placebo group, adjusted for the ratio of the follow-up period in each group.
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Comparison groups |
RotaTeq™ Per Protocol v Placebo Per Protocol
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Number of subjects included in analysis |
711
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.001 [1] | |||||||||
Method |
Exact Conditional Test | |||||||||
Parameter type |
Vaccine Efficacy | |||||||||
Point estimate |
74.5
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
39.9 | |||||||||
upper limit |
90.6 | |||||||||
| Notes [1] - Hypothesis: Efficacy >0%. Based on p< 1/(1+k); p = proportion of participants with outcome in vaccine group relative to total number of participants with outcome; k = ratio of follow-up time; placebo/vaccine. Based on conditional binomial approach. |
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End point title |
Incidence Rate of Moderate to Severe Rotavirus Gastroenteritis Caused by Rotavirus Serotypes G1, G2, G3, G4 and G-serotypes Associated With P1A | |||||||||
End point description |
Moderate to severe cases of rotavirus gastroenteritis caused by G1, G2, G3, G4 or G-serotypes associated with P1A occurring at least 14 days postdose 3 in the per-protocol population using per-protocol case definition. Severity score was calculated based on frequency and duration of diarrhea, vomiting, elevated temperature, and behavioral changes. Score of >8 and <=16 was considered moderate, and >16 was considered severe. The population analyzed was per-protocol participants except those unevaluable due to 1) detection of wild-type rotavirus in stool prior to 14 days Postdose 3, 2) incomplete clinical and/or laboratory results, or 3) stool samples collected out of day range.
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End point type |
Secondary
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End point timeframe |
From 14 days Postdose 3 onward
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Statistical analysis title |
Vaccine Efficacy | |||||||||
Statistical analysis description |
Efficacy = 1-RR, expressed as a percentage; the RR is the incidence in the vaccine group / the incidence in the placebo group, adjusted for the ratio of the follow-up period in each group.
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Comparison groups |
RotaTeq™ Per Protocol v Placebo Per Protocol
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Number of subjects included in analysis |
710
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.001 [2] | |||||||||
Method |
Exact Conditional Test | |||||||||
Parameter type |
Vaccine Efficacy | |||||||||
Point estimate |
80.2
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
47.4 | |||||||||
upper limit |
94.1 | |||||||||
| Notes [2] - Hypothesis: Efficacy >0%. Based on p< 1/(1+k); p = proportion of participants with outcome in vaccine group relative to total number of participants with outcome; k = ratio of follow-up time; placebo/vaccine. Based on conditional binomial approach. |
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End point title |
Incidence Rate of Severe Rotavirus Gastroenteritis Caused by Rotavirus Serotypes G1, G2, G3, G4 and G-serotypes Associated With P1A | |||||||||
End point description |
Severe cases of rotavirus gastroenteritis caused by G1, G2, G3, G4 or G-serotypes associated with P1A occurring at least 14 days postdose 3 in the per-protocol population using per-protocol case definition. Severity score was calculated based on frequency and duration of diarrhea, vomiting, elevated temperature, and behavioral changes. Score of >8 and <=16 was considered moderate, and >16 was considered severe. The population analyzed was per-protocol participants except those unevaluable due to 1) detection of wild-type rotavirus in stool prior to 14 days Postdose 3, 2) incomplete clinical and/or laboratory results, or 3) stool samples collected out of day range.
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End point type |
Secondary
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End point timeframe |
From 14 days Postdose 3 onward
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Statistical analysis title |
Vaccine Efficacy | |||||||||
Statistical analysis description |
Efficacy = 1-RR, expressed as a percentage; the RR is the incidence in the vaccine group / the incidence in the placebo group, adjusted for the ratio of the follow-up period in each group.
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Comparison groups |
RotaTeq™ Per Protocol v Placebo Per Protocol
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Number of subjects included in analysis |
709
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.001 [3] | |||||||||
Method |
Exact Conditional Test | |||||||||
Parameter type |
Vaccine Efficacy | |||||||||
Point estimate |
100
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
55.4 | |||||||||
upper limit |
100 | |||||||||
| Notes [3] - Hypothesis: Efficacy >0%. Based on p< 1/(1+k); p = proportion of participants with outcome in vaccine group relative to total number of participants with outcome; k = ratio of follow-up time; placebo/vaccine. Based on conditional binomial approach. |
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Adverse events information
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Timeframe for reporting adverse events |
14-day period following each vaccination. Any death, Vaccine related serious adverse events (AEs) and Intussusception were collected during the study period.
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Adverse event reporting additional description |
Parents/guardians were asked to record AEs on a standardized Vaccine Report Card (VRC) up to 14 days after each vaccination. Solicited AEs included diarrhea and vomiting. Temperature was also measured daily for 7 days after each vaccination.
The number of participants exposed is the number of participants who received study treatment.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
At least one dose of placebo administered 28 to 70 days apart, beginning on Day 1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
RotaTeq™
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Reporting group description |
At least one dose of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, beginning on Day 1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
