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    Clinical Trial Results:
    Single and Multiple Dose Pharmacokinetics and Safety Study of Rabeprazole Sodium in 12 to 16 Year Old Subjects

    Summary
    EudraCT number
    2016-001878-15
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    08 Jun 2004

    Results information
    Results version number
    v1(current)
    This version publication date
    29 Jul 2016
    First version publication date
    29 Jul 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    E3810-A001-119
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Eisai Medical Research Inc.
    Sponsor organisation address
    100 Tice Boulevard, Woodcliff Lake, United States, 07677
    Public contact
    Eisai Medical Information, Eisai Medical Research Inc., 1 8882742378, esi_medinfo@eisai.com
    Scientific contact
    Eisai Medical Information, Eisai Medical Research Inc., 1 8882742378, esi_medinfo@eisai.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000055-PIP01-07
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Jun 2004
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Jun 2004
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To characterize the PK profile of single and repeated doses of rabeprazole sodium in participants 12 to 16 years of age with a diagnosis of, or symptoms of, gastroesophageal reflux disease (GERD).
    Protection of trial subjects
    This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states. - Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP Subject Information and Informed Consent.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    04 Sep 2003
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 24
    Worldwide total number of subjects
    24
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    24
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Twenty-four children 12 to 16 years of age who had a diagnosis of, or symptoms of, GERD were enrolled into the study. Twelve participants were randomized to the rabeprazole 10-mg group and 12 participants were randomized to the rabeprazole 20-mg group. All 24 participants completed the study; no early terminations or deaths were observed.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    10 mg Rabeprazole sodium
    Arm description
    On Day 1, after an overnight fast and after completion of pre-dose evaluations (physical examinations, vital signs, electrocardiogram, and clinical laboratory testing), rabeprazole sodium was administered orally with water in the morning. Participants were allowed clear liquids 2 hours after study drug and lunch 4 hours after study drug. Subsequent study drug was administered in the morning on Days 2 to 4, and on Day 5 following an overnight fast. Alternatively, participants could continue taking a single daily dose of rabeprazole on Day 6, fast overnight and return to the site on Day 7 instead of Day 5 for the final dose of study drug and the second pharmacokinetic (PK) blood draw and laboratory testing. Participants returned to the site in a fasted state the morning of Day 6 (or Day 8) for the 24-hour post-dose PK blood draw and laboratory testing. Participants were discharged from the study after the final safety evaluation and study termination procedures were performed.
    Arm type
    Experimental

    Investigational medicinal product name
    Rabeprazole sodium
    Investigational medicinal product code
    E3810
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Rabeprazole sodium was administered to the participants in an ascending dose fashion, beginning with 10 mg. Administration of the 10 mg dose was completed and preliminary safety data was evaluated before administration of the 20 mg dose was initiated. Each participant participated for a total of up to 3 weeks, including the screening visit, which was scheduled within 2 weeks of study drug administration.

    Arm title
    20 mg Rabeprazole sodium
    Arm description
    On Day 1, after an overnight fast and after completion of pre-dose evaluations (physical examinations, vital signs, electrocardiogram, and clinical laboratory testing), rabeprazole sodium was administered orally with water in the morning. Participants were allowed clear liquids 2 hours after study drug and lunch 4 hours after study drug. Subsequent study drug was administered in the morning on Days 2 to 4, and on Day 5 following an overnight fast. Alternatively, participants could continue taking a single daily dose of rabeprazole on Day 6, fast overnight and return to the site on Day 7 instead of Day 5 for the final dose of study drug and the second pharmacokinetic (PK) blood draw and laboratory testing. Participants returned to the site in a fasted state the morning of Day 6 (or Day 8) for the 24-hour post-dose PK blood draw and laboratory testing. Participants were discharged from the study after the final safety evaluation and study termination procedures were performed.
    Arm type
    Experimental

    Investigational medicinal product name
    Rabeprazole sodium
    Investigational medicinal product code
    E3810
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Rabeprazole sodium was administered to the participants in an ascending dose fashion, beginning with 10 mg. Administration of the 10 mg dose was completed and preliminary safety data was evaluated before administration of the 20 mg dose was initiated. Each participant participated for a total of up to 3 weeks, including the screening visit, which was scheduled within 2 weeks of study drug administration.

    Number of subjects in period 1
    10 mg Rabeprazole sodium 20 mg Rabeprazole sodium
    Started
    12
    12
    Completed
    12
    12

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    10 mg Rabeprazole sodium
    Reporting group description
    On Day 1, after an overnight fast and after completion of pre-dose evaluations (physical examinations, vital signs, electrocardiogram, and clinical laboratory testing), rabeprazole sodium was administered orally with water in the morning. Participants were allowed clear liquids 2 hours after study drug and lunch 4 hours after study drug. Subsequent study drug was administered in the morning on Days 2 to 4, and on Day 5 following an overnight fast. Alternatively, participants could continue taking a single daily dose of rabeprazole on Day 6, fast overnight and return to the site on Day 7 instead of Day 5 for the final dose of study drug and the second pharmacokinetic (PK) blood draw and laboratory testing. Participants returned to the site in a fasted state the morning of Day 6 (or Day 8) for the 24-hour post-dose PK blood draw and laboratory testing. Participants were discharged from the study after the final safety evaluation and study termination procedures were performed.

    Reporting group title
    20 mg Rabeprazole sodium
    Reporting group description
    On Day 1, after an overnight fast and after completion of pre-dose evaluations (physical examinations, vital signs, electrocardiogram, and clinical laboratory testing), rabeprazole sodium was administered orally with water in the morning. Participants were allowed clear liquids 2 hours after study drug and lunch 4 hours after study drug. Subsequent study drug was administered in the morning on Days 2 to 4, and on Day 5 following an overnight fast. Alternatively, participants could continue taking a single daily dose of rabeprazole on Day 6, fast overnight and return to the site on Day 7 instead of Day 5 for the final dose of study drug and the second pharmacokinetic (PK) blood draw and laboratory testing. Participants returned to the site in a fasted state the morning of Day 6 (or Day 8) for the 24-hour post-dose PK blood draw and laboratory testing. Participants were discharged from the study after the final safety evaluation and study termination procedures were performed.

    Reporting group values
    10 mg Rabeprazole sodium 20 mg Rabeprazole sodium Total
    Number of subjects
    12 12 24
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    13.9 (12 to 16) 14.5 (12 to 16) -
    Gender categorical
    Units: Subjects
        Female
    8 5 13
        Male
    4 7 11

    End points

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    End points reporting groups
    Reporting group title
    10 mg Rabeprazole sodium
    Reporting group description
    On Day 1, after an overnight fast and after completion of pre-dose evaluations (physical examinations, vital signs, electrocardiogram, and clinical laboratory testing), rabeprazole sodium was administered orally with water in the morning. Participants were allowed clear liquids 2 hours after study drug and lunch 4 hours after study drug. Subsequent study drug was administered in the morning on Days 2 to 4, and on Day 5 following an overnight fast. Alternatively, participants could continue taking a single daily dose of rabeprazole on Day 6, fast overnight and return to the site on Day 7 instead of Day 5 for the final dose of study drug and the second pharmacokinetic (PK) blood draw and laboratory testing. Participants returned to the site in a fasted state the morning of Day 6 (or Day 8) for the 24-hour post-dose PK blood draw and laboratory testing. Participants were discharged from the study after the final safety evaluation and study termination procedures were performed.

    Reporting group title
    20 mg Rabeprazole sodium
    Reporting group description
    On Day 1, after an overnight fast and after completion of pre-dose evaluations (physical examinations, vital signs, electrocardiogram, and clinical laboratory testing), rabeprazole sodium was administered orally with water in the morning. Participants were allowed clear liquids 2 hours after study drug and lunch 4 hours after study drug. Subsequent study drug was administered in the morning on Days 2 to 4, and on Day 5 following an overnight fast. Alternatively, participants could continue taking a single daily dose of rabeprazole on Day 6, fast overnight and return to the site on Day 7 instead of Day 5 for the final dose of study drug and the second pharmacokinetic (PK) blood draw and laboratory testing. Participants returned to the site in a fasted state the morning of Day 6 (or Day 8) for the 24-hour post-dose PK blood draw and laboratory testing. Participants were discharged from the study after the final safety evaluation and study termination procedures were performed.

    Subject analysis set title
    E3810 (10 mg Group)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The evaluable population was used and included all participants who have the following characteristics: compliant (participants who discontinue study drug for a serious adverse event were included, regardless of duration of dosing) and those who had no serious protocol violation. Participants in the 10 mg Group were analyzed for both E3810 and PTBI.

    Subject analysis set title
    PTBI (10 mg Group)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The evaluable population was used and included all participants who have the following characteristics: compliant (participants who discontinue study drug for a serious adverse event were included, regardless of duration of dosing) and those who had no serious protocol violation. Participants in the 10 mg Group were analyzed for both E3810 and 2-[[[ 4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]thio ]-!H-benzimidazole (PTBI).

    Subject analysis set title
    E3810 (20 mg Group)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The evaluable population was used and included all participants who have the following characteristics: compliant (participants who discontinue study drug for a serious adverse event were included, regardless of duration of dosing) and those who had no serious protocol violation. Participants in the 20 mg Group were analyzed for both E3810 and PTBI.

    Subject analysis set title
    PTBI (20 mg Group)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The evaluable population was used and included all participants who have the following characteristics: compliant (participants who discontinue study drug for a serious adverse event were included, regardless of duration of dosing) and those who had no serious protocol violation. Participants in the 20 mg Group were analyzed for both E3810 and PTBI.

    Primary: Mean Area Under the Plasma Concentration-Time Curve from zero to Time t (AUC (0-t))

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    End point title
    Mean Area Under the Plasma Concentration-Time Curve from zero to Time t (AUC (0-t)) [1]
    End point description
    Blood samples were obtained pre-dose and post-dose, at specified time points. Rabeprazole plasma concentration and its metabolite, rabeprazole thioether (PTBI), was measured by a validated liquid chromatography/tandem mass spectrometry system (LC/MS/MS). The pharmacokinetic (PK) parameter, AUC was calculated by the linear/log trapezoidal rule and analyzed using non-compartmental methods.
    End point type
    Primary
    End point timeframe
    Day 1 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, and 12 hours post-dose); Days 2, 3 & 4 (pre-dose); Day 5 (or 7) (time points same as for Day 1); Day 6 (or 8) post-dose
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not done.
    End point values
    E3810 (10 mg Group) PTBI (10 mg Group) E3810 (20 mg Group) PTBI (20 mg Group)
    Number of subjects analysed
    12
    12
    12
    12
    Units: ng*hr/mL
    geometric mean (standard error)
        Day 1 (n = 8, 8, 11, 8)
    305 ± 37.91
    228.9 ± 42.84
    557.8 ± 109.8
    823.4 ± 205.2
        Day 5 or 7 (n = 9, 10, 9, 9)
    249.8 ± 31.74
    184.6 ± 40.1
    828.4 ± 176.1
    727.1 ± 231.4
    No statistical analyses for this end point

    Primary: Mean Maximum Drug Plasma Concentration (Cmax)

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    End point title
    Mean Maximum Drug Plasma Concentration (Cmax) [2]
    End point description
    Cmax was obtained directly from the data with and without interpolation.
    End point type
    Primary
    End point timeframe
    Day 1 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, and 12 hours post-dose); Days 2, 3 & 4 (pre-dose); Day 5 (or 7) (time points same as for Day 1); Day 6 (or 8) post-dose
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not done.
    End point values
    E3810 (10 mg Group) PTBI (10 mg Group) E3810 (20 mg Group) PTBI (20 mg Group)
    Number of subjects analysed
    12
    12
    12
    12
    Units: ng/mL
    geometric mean (standard error)
        Day 1 (n = 12, 12, 12, 12)
    186.6 ± 25.46
    39.12 ± 5.767
    319 ± 48.38
    108.8 ± 19.48
        Day 5 or 7 (n = 11, 11, 12, 12)
    184.1 ± 26.58
    31.37 ± 3.627
    460.4 ± 85.82
    120.3 ± 19.96
    No statistical analyses for this end point

    Primary: Mean Time to Peak Concentration (Tmax)

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    End point title
    Mean Time to Peak Concentration (Tmax) [3]
    End point description
    T max was obtained directly from the data with and without interpolation.
    End point type
    Primary
    End point timeframe
    Day 1 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, and 12 hours post-dose); Days 2, 3 & 4 (pre-dose); Day 5 (or 7) (time points same as for Day 1); Day 6 (or 8) post-dose
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not done.
    End point values
    E3810 (10 mg Group) PTBI (10 mg Group) E3810 (20 mg Group) PTBI (20 mg Group)
    Number of subjects analysed
    12
    12
    12
    12
    Units: Hours
    geometric mean (standard error)
        Day 1 (n = 12, 12, 12, 12)
    3.333 ± 0.322
    4.625 ± 0.37
    3.958 ± 0.199
    5.5 ± 0.275
        Day 5 or 7 (n = 11, 11, 12, 12)
    3.409 ± 0.517
    4.273 ± 0.464
    4.125 ± 0.449
    5.75 ± 0.656
    No statistical analyses for this end point

    Primary: Mean Apparent Elimination Half-life (t1/2)

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    End point title
    Mean Apparent Elimination Half-life (t1/2) [4]
    End point description
    The elimination half-life is the time it takes for the concentration of study drug to drop to 50% of its value in plasma. The apparent elimination half-life (t1/2) during the terminal disposition phase was defined as 0.693λz.
    End point type
    Primary
    End point timeframe
    Day 1 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, and 12 hours post-dose); Days 2, 3 & 4 (pre-dose); Day 5 (or 7) (time points same as for Day 1); Day 6 (or 8) post-dose
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not done.
    End point values
    E3810 (10 mg Group) PTBI (10 mg Group) E3810 (20 mg Group) PTBI (20 mg Group)
    Number of subjects analysed
    12
    12
    12
    12
    Units: Hour
    geometric mean (standard error)
        Day 1 (n = 8, 8, 11, 8)
    0.545 ± 0.042
    2.151 ± 0.192
    1.01 ± 0.247
    4.5 ± 0.683
        Day 5 or 7 (n = 9, 10, 9, 9)
    0.56 ± 0.059
    2.49 ± 0.355
    0.99 ± 0.166
    3.06 ± 0.491
    No statistical analyses for this end point

    Primary: Mean Apparent Oral Clearance by Weight (CL/F/Wt)

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    End point title
    Mean Apparent Oral Clearance by Weight (CL/F/Wt) [5]
    End point description
    Blood samples were obtained pre-dose and at specified time points. CL/F was calculated based on the last day of multiple dosing. On Day 1 E3810 and PTBI was not calculated as n = 0, therefore zero was added as a placeholder.
    End point type
    Primary
    End point timeframe
    Day 1 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, and 12 hours post-dose); Days 2, 3 & 4 (pre-dose); Day 5 (or 7) (time points same as for Day 1); Day 6 (or 8) post-dose
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not done.
    End point values
    E3810 (10 mg Group) PTBI (10 mg Group) E3810 (20 mg Group) PTBI (20 mg Group)
    Number of subjects analysed
    12
    12
    12
    12
    Units: mL/minute/kg
    geometric mean (standard error)
        Day 1 (n = 0, 0, 0, 0)
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
        Day 5 or 7 (n = 9, 10, 9, 9)
    12.58 ± 1.826
    21.04 ± 3.938
    10.14 ± 2.302
    14.41 ± 4.372
    No statistical analyses for this end point

    Primary: Mean Volume of Distribution for Extravascular Administration (Vz/F)

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    End point title
    Mean Volume of Distribution for Extravascular Administration (Vz/F) [6]
    End point description
    Vz/F was calculated based on the last day of multiple dosing. On Day 1, E3810 and PTBI was not calculated as n = 0, therefore zero was added as a placeholder.
    End point type
    Primary
    End point timeframe
    Day 1 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, and 12 hours post-dose); Days 2, 3 & 4 (pre-dose); Day 5 (or 7) (time points same as for Day 1); Day 6 (or 8) post-dose
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not done.
    End point values
    E3810 (10 mg Group) PTBI (10 mg Group) E3810 (20 mg Group) PTBI (20 mg Group)
    Number of subjects analysed
    12
    12
    12
    12
    Units: mL
    geometric mean (standard error)
        Day 1 (n = 0, 0, 0, 0)
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
        Day 5 or 7 (n = 9, 10, 9, 9)
    33907 ± 3357
    230000 ± 24309
    39600 ± 5994
    169000 ± 27317
    No statistical analyses for this end point

    Secondary: Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    Safety variables assessed included: occurrence of AEs, SAEs, and Treatment-Emergent Signs and Symptoms (TESS), and changes in physical examination findings, clinical laboratory test results, vital signs, and electrocardiogram (ECG) evaluations. AEs were tabulated as TESS for this study. The incidence of TESS were summarized by body system, and by severity and relationship to study drug. A participant having the same TESS more than once over the course of the study was counted only once in the incidence calculation for that TESS. Also, if a participant had more than one TESS in a single body system, the participants was counted only once in the total number of participants with TESS for that body system. If a participant had a TESS more than once in the study, the occurrence with the maximum severity was used in the calculation of the incidence of individual TESS by severity. For drug relationship, the TESS considered most closely related to study drug was used.
    End point type
    Secondary
    End point timeframe
    Screening Visit, Days 1 through 6 (or Day 8, as appropriate)
    End point values
    10 mg Rabeprazole sodium 20 mg Rabeprazole sodium
    Number of subjects analysed
    12
    12
    Units: Participants
    number (not applicable)
        Total TESS
    6
    5
        Total Treatment Related TESS
    3
    2
        Total SAEs
    0
    0
        Withdrawn due to AEs
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected for approximately 9 months.
    Adverse event reporting additional description
    Safety variables assessed during this study consisted of the following: occurrence of AEs, serious AEs, and Treatment-emergent Signs an Symptoms (TESS), and changes in physical examination findings, clinical laboratory test results, vital signs and electrocardiogram (ECG) evaluations.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    6.1
    Reporting groups
    Reporting group title
    20 mg Rabeprazole sodium
    Reporting group description
    On Day 1, after an overnight fast and after completion of pre-dose evaluations (physical examinations, vital signs, electrocardiogram, and clinical laboratory testing), rabeprazole sodium was administered orally with water in the morning. Participants were allowed clear liquids 2 hours after study drug and lunch 4 hours after study drug. Subsequent study drug was administered in the morning on Days 2 to 4, and on Day 5 following an overnight fast. Alternatively, participants could continue taking a single daily dose of rabeprazole on Day 6, fast overnight and return to the site on Day 7 instead of Day 5 for the final dose of study drug and the second pharmacokinetic (PK) blood draw and laboratory testing. Participants returned to the site in a fasted state the morning of Day 6 (or Day 8) for the 24-hour post-dose PK blood draw and laboratory testing. Participants were discharged from the study after the final safety evaluation and study termination procedures were performed.

    Reporting group title
    10 mg Rabeprazole sodium
    Reporting group description
    On Day 1, after an overnight fast and after completion of pre-dose evaluations (physical examinations, vital signs, electrocardiogram, and clinical laboratory testing), rabeprazole sodium was administered orally with water in the morning. Participants were allowed clear liquids 2 hours after study drug and lunch 4 hours after study drug. Subsequent study drug was administered in the morning on Days 2 to 4, and on Day 5 following an overnight fast. Alternatively, participants could continue taking a single daily dose of rabeprazole on Day 6, fast overnight and return to the site on Day 7 instead of Day 5 for the final dose of study drug and the second pharmacokinetic (PK) blood draw and laboratory testing. Participants returned to the site in a fasted state the morning of Day 6 (or Day 8) for the 24-hour post-dose PK blood draw and laboratory testing. Participants were discharged from the study after the final safety evaluation and study termination procedures were performed.

    Serious adverse events
    20 mg Rabeprazole sodium 10 mg Rabeprazole sodium
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    20 mg Rabeprazole sodium 10 mg Rabeprazole sodium
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 12 (33.33%)
    6 / 12 (50.00%)
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 12 (25.00%)
         occurrences all number
    1
    3
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Periorbital oedema
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Feb 2004
    •The number of study centers was revised from up to 8 to up to 9 study centers due to slower than anticipated subject enrollment. •The requirement that pretest evaluations be performed and study drug be administered at 8 AM was changed to “in the morning” on Day 1, Days 3 and 4, and Days 5 and 6, from 8 AM to “approximately the same time in the morning as on Day 1.” This change was also made for subjects who returned to the site on Day 7 (8 AM in the original protocol was changed to “approximately the same time as on Day 1”). This revision was made to allow for the variability in subjects’ schedule, especially during the school year. •Inclusion criterion #7 that required normal laboratory findings in the original Study Protocol was deleted in Amendment 01. This change was made to allow screening of subjects whose laboratory test results values were outside the defined normal range but considered to be “normal” for that subject or were values that were not clinically significant. •Because of the high frequency of smoking and alcohol use encountered the population under study, Exclusion criterion 3 was modified. The original Study Protocol stated that subjects with a known or suspected history of tobacco use, alcohol, or drug misuse within the past three months were excluded. Amendment 01 changed this to the following: “subjects who were unwilling or unable to refrain from smoking or drinking alcohol starting from 48 hours prior to screening and dosing, through the end of the study, and/or a positive urine drug screen were excluded.” •Based on the change to Exclusion criterion 3, Section 4.4 (Prohibitions and Restrictions during the Study) of the Study Protocol, had the following addition in Amendment 01: “subjects may not receive any recreational drugs, tobacco, and alcohol during study participation and within 48 hours of admission to the clinical site.”
    11 Feb 2004
    Continuation of Amendment 1: • Based on the change to Section 4.4 of the Study Protocol noted above, the following statement was deleted from Section 4.5 (Concomitant Medications): "subjects may not receive any recreational drugs and alcohol during study participation and within 72 hours of admission to the clinical site." • The list of drug substances to be assayed in the urine drug screen (Section 7.5.4 of the Study Protocol, Appendix 16.1.1) was modified to exclude nicotine/cotinine in Amendment 0 l. • Appendix 5 was added in Amendment 01 to provide the procedure for processing samples for CYP2C 19 genotyping. • In Amendment 01, revisions for the processing, storage, and shipping of the blood samples for PK assays were made to Appendix IV. The laboratory processing these samples was changed from PRACS Institute, Ltd. to Quest Pharmaceutical Services, L.C.C. • New contact information for responsible EMR personnel was provided in Amendment 01. There were no changes to the planned analyses.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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