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    Clinical Trial Results:
    A Phase III, Randomized, Double-Blind, Clinical Trial to Study the Efficacy and Safety of MK-0431D (a fixed-dose combination [FDC] of sitagliptin and simvastatin) for the Treatment of Patients With Type 2 Diabetes Mellitus (T2DM) with Inadequate Glycemic Control on Metformin Monotherapy

    Summary
    EudraCT number
    		 2012-001868-29
    Trial protocol
    		 LT   LV   HU   CZ   PL   IT  
    Global end of trial date
    01 Nov 2013

    Results information
    Results version number
    		 v2(current)
    This version publication date
    06 May 2016
    First version publication date
    18 Mar 2015
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Update Record

    Trial information

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    Trial identification
    Sponsor protocol code
    MK-0431D-266
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01678820
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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
    01 Nov 2013
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Nov 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Nov 2013
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    1. To assess the effect of MK-0431D compared to sitagliptin alone on hemoglobin A1c (A1C). 2. To assess the safety and tolerability of MK-0431D.
    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. The following additional measure defined for this individual study was in place for the protection of trial subjects: participants not meeting specific glycemic goals received rescue therapy initiated with glimepiride (open-label, supplied locally).
    Background therapy
    		 Participants will continue on their stable, pre-screening metformin daily dose of >= 1500 mg for at least 12 weeks prior to randomization and during the study.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Oct 2012
    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
    Poland: 6
    Country: Number of subjects enrolled
    Czech Republic: 11
    Country: Number of subjects enrolled
    Hungary: 18
    Country: Number of subjects enrolled
    Latvia: 1
    Country: Number of subjects enrolled
    Lithuania: 2
    Country: Number of subjects enrolled
    Macedonia, the former Yugoslav Republic of: 3
    Country: Number of subjects enrolled
    Malaysia: 1
    Country: Number of subjects enrolled
    Puerto Rico: 5
    Country: Number of subjects enrolled
    Romania: 11
    Country: Number of subjects enrolled
    Colombia: 3
    Country: Number of subjects enrolled
    Croatia: 2
    Country: Number of subjects enrolled
    Korea, Republic of: 1
    Country: Number of subjects enrolled
    South Africa: 17
    Country: Number of subjects enrolled
    United States: 218
    Worldwide total number of subjects
    299
    EEA total number of subjects
    51
    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)
    0
    Adults (18-64 years)
    251
    From 65 to 84 years
    48
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 All participants randomized population.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sitagliptin/Simvastatin FDC
    Arm description
    		 Sitagliptin 100 mg/simvastatin 40 mg fixed dose combination (FDC) plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be uptitrated to 6 mg once daily) as rescue therapy.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sitagliptin/Simvastatin FDC
    Investigational medicinal product code
    Other name
    MK-0431D
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet administered once daily in the evening.

    Investigational medicinal product name
    Placebo to simvastatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to simvastatin administered once daily in the evening.

    Investigational medicinal product name
    Placebo to sitagliptin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to sitagliptin administered once daily in the evening.

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants will continue on their stable, pre-screening metformin daily dose of >= 1500 mg for at least 12 weeks prior to randomization and during the study.

    Investigational medicinal product name
    Glimepiride
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Following randomization, participants requiring glycemic rescue may receive open-label glimepiride initiated at a dose of 1 mg/day or 2 mg/day which may be up-titrated to 6 mg/day taken once daily with breakfast or the first main meal of the day.

    Arm title
    		 Sitagliptin
    Arm description
    		 Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Sitagliptin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Sitagliptin 100 mg oral tablet administered once daily in the evening.

    Investigational medicinal product name
    Placebo to simvastatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to simvastatin administered once daily in the evening.

    Investigational medicinal product name
    Placebo to sitagliptin/simvastatin FDC
    Investigational medicinal product code
    Other name
    MK-0431D
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo to sitagliptin/simvastatin FDC tablet administered once daily in the evening.

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants will continue on their stable, pre-screening metformin daily dose of >= 1500 mg for at least 12 weeks prior to randomization and during the study.

    Investigational medicinal product name
    Glimepiride
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Following randomization, participants requiring glycemic rescue may receive open-label glimepiride initiated at a dose of 1 mg/day or 2 mg/day which may be up-titrated to 6 mg/day taken once daily with breakfast or the first main meal of the day.

    Arm title
    		 Simvastatin
    Arm description
    		 Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Simvastatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Simvastatin 40 mg tablet administered orally once daily in the evening.

    Investigational medicinal product name
    Placebo to sitagliptin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to sitagliptin administered once daily in the evening.

    Investigational medicinal product name
    Placebo to sitagliptin/simvastatin FDC
    Investigational medicinal product code
    Other name
    MK-0431D
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo to sitagliptin/simvastatin FDC tablet administered once daily in the evening.

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants will continue on their stable, pre-screening metformin daily dose of >= 1500 mg for at least 12 weeks prior to randomization and during the study.

    Investigational medicinal product name
    Glimepiride
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Following randomization, participants requiring glycemic rescue may receive open-label glimepiride initiated at a dose of 1 mg/day or 2 mg/day which may be up-titrated to 6 mg/day taken once daily with breakfast or the first main meal of the day.

    Number of subjects in period 1
    		Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Started
    100
    99
    100
    Treated with double-blind study drug
    100
    97
    98
    Completed
    38
    36
    43
    Not completed
    62
    63
    57
         Consent withdrawn by subject
    2
    5
    2
         Physician decision
    -
    -
    1
         Not treated with double-blind study drug
    -
    2
    2
         Adverse event
    2
    2
    2
         Non-compliance with study drug
    -
    1
    -
         Protocol Specified Criteria
    2
    3
    1
         Study Terminated by Sponsor
    45
    43
    43
         Lost to follow-up
    7
    2
    2
         Protocol deviation
    4
    5
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Sitagliptin/Simvastatin FDC
    Reporting group description
    		 Sitagliptin 100 mg/simvastatin 40 mg fixed dose combination (FDC) plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be uptitrated to 6 mg once daily) as rescue therapy.

    Reporting group title
    Sitagliptin
    Reporting group description
    		 Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

    Reporting group title
    Simvastatin
    Reporting group description
    		 Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

    Reporting group values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin Total
    Number of subjects
    		 100 99 100 299
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 54.9 ( 10.2 ) 54.2 ( 10.3 ) 54.9 ( 10 ) -
    Gender categorical
    Units: Subjects
        Female
    		 45 52 49 146
        Male
    		 55 47 51 153
    Hemoglobin A1c (A1C)
    Units: percent
        arithmetic mean (standard deviation)
    		 8.16 ( 0.94 ) 8.15 ( 1.09 ) 8.22 ( 1.19 ) -
    Fasting plasma glucose (FPG)
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 169.9 ( 42.3 ) 175.9 ( 48.6 ) 175.7 ( 49.3 ) -
    Low-density lipoprotein cholesterol (LDL-C)
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 106.5 ( 26.7 ) 103.9 ( 24.2 ) 100.9 ( 22 ) -
    Total cholesterol (TC)
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 189.3 ( 30.9 ) 187.7 ( 29.6 ) 183.5 ( 28.4 ) -
    Apolipoprotein B (Apo B)
    Population includes all randomized participants with data. Sitagliptin, n=95.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 97.8 ( 19 ) 95.4 ( 19 ) 94.1 ( 17.2 ) -
    Non high-density lipoprotein cholesterol (non-HDL-C)
    Population includes all randomized participants with data. Sitagliptin, n=97.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 141.7 ( 30.9 ) 139.5 ( 29.9 ) 136.5 ( 27.1 ) -
    Triglycerides (TG)
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 177.4 ( 101.2 ) 180.8 ( 119.1 ) 184.2 ( 118.6 ) -
    High-density lipoprotein cholesterol (HDL-C)
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 47.6 ( 11.3 ) 48.2 ( 12.1 ) 47 ( 11.2 ) -
    Very low-density lipoprotein cholesterol (VLDL-C)
    Population includes all randomized participants with data. Sitagliptin, n=97.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 35.4 ( 18.8 ) 35.8 ( 20.4 ) 35.7 ( 18.8 ) -

    End points

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    End points reporting groups
    Reporting group title
    Sitagliptin/Simvastatin FDC
    Reporting group description
    		 Sitagliptin 100 mg/simvastatin 40 mg fixed dose combination (FDC) plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be uptitrated to 6 mg once daily) as rescue therapy.

    Reporting group title
    Sitagliptin
    Reporting group description
    		 Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

    Reporting group title
    Simvastatin
    Reporting group description
    		 Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

    Primary: Change from baseline in A1C at Week 16 (sitagliptin/simvastatin FDC vs. sitagliptin)

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    End point title
    		 Change from baseline in A1C at Week 16 (sitagliptin/simvastatin FDC vs. sitagliptin) [1]
    End point description
    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary endpoint only includes results for sitagliptin/simvastatin FDC vs. sitagliptin. Results for simvastatin are presented below under secondary endpoints. Full analysis set (FAS) population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Primary
    End point timeframe
    Baseline and Week 16
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This primary endpoint only includes results for sitagliptin/simvastatin FDC vs. sitagliptin. Results for simvastatin are presented under secondary endpoints.
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin
    Number of subjects analysed
    100
    97
    Units: percent
        least squares mean (confidence interval 95%)
    -0.41 (-0.64 to -0.17)
    -0.59 (-0.83 to -0.36)
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    P-value
    		 = 0.267 [3]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.52
    Notes
    [2] - Due to inadequate sample size, the primary hypothesis of non-inferiority was not tested. Nominal p-value is provided.
    [3] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.

    Primary: Number of participants who experienced at least one adverse event (AE)

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    End point title
    		 Number of participants who experienced at least one adverse event (AE)
    End point description
    Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. All participants as treated population defined as all randomized participants who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    Up to 16 weeks for non-serious AEs; up to 18 weeks for serious AEs
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    97
    98
    Units: Participants
    13
    13
    17
    Statistical analysis title
    		 Difference in percents
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    Method
    Parameter type
    		 Difference in percents
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.2
         upper limit
    		 9.3
    Notes
    [4] - Based on Miettinen & Nurminen method
    Statistical analysis title
    		 Difference in percents
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    Method
    Parameter type
    		 Difference in percents
    Point estimate
    -4.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.7
         upper limit
    		 5.8
    Notes
    [5] - Based on Miettinen & Nurminen method

    Primary: Number of participants who discontinued study drug due to an adverse event

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    End point title
    		 Number of participants who discontinued study drug due to an adverse event [6]
    End point description
    Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. All participants as treated population defined as all randomized participants who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    Up to 16 weeks
    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: As pre-specified in the protocol, 95% confidence intervals were only provided for events with an incidence of at least 4 participants in at least one of the treatment arms.
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    97
    98
    Units: Participants
    2
    1
    2
    No statistical analyses for this end point

    Secondary: Change from baseline in A1C at Week 16 (sitagliptin/simvastatin FDC vs. simvastatin)

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    End point title
    		 Change from baseline in A1C at Week 16 (sitagliptin/simvastatin FDC vs. simvastatin) [7]
    End point description
    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. simvastatin. Results for sitagliptin are presented above under primary outcome measures. FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This secondary endpoint only includes results for sitagliptin/simvastatin FDC vs. simvastatin. Results for sitagliptin are presented under primary endpoints.
    End point values
    		 Sitagliptin/Simvastatin FDC Simvastatin
    Number of subjects analysed
    100
    98
    Units: percent
        least squares mean (confidence interval 95%)
    -0.41 (-0.64 to -0.17)
    0.21 (-0.02 to 0.45)
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 < 0.001 [9]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    -0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.95
         upper limit
    		 -0.28
    Notes
    [8] - Due to inadequate sample size, the secondary hypothesis was not tested. Nominal p-value is provided.
    [9] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.

    Secondary: Change from baseline in FPG at Week 16

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    End point title
    		 Change from baseline in FPG at Week 16
    End point description
    Change from baseline reflects the Week 16 value minus the Week 0 value. FAS population defined as all randomized participants who took at least one dose of study drug and who had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    97
    98
    Units: mg/dL
        least squares mean (confidence interval 95%)
    -7.9 (-21 to 5.2)
    -9.6 (-23.4 to 4.1)
    21.3 (7.9 to 34.7)
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 other [10]
    P-value
    		 = 0.856 [11]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.1
         upper limit
    		 20.6
    Notes
    [10] - There is no hypothesis comparing Sitagliptin/Simvastatin vs. Sitagliptin for FPG. Nominal p-value is provided.
    [11] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [12]
    P-value
    		 = 0.002 [13]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    -29.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -47.9
         upper limit
    		 -10.6
    Notes
    [12] - There is no hypothesis comparing Sitagliptin/Simvastatin vs. Simvastatin for FPG. Nominal p-value is provided.
    [13] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.

    Secondary: Percent change from baseline in LDL-C at Week 16

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    End point title
    		 Percent change from baseline in LDL-C at Week 16
    End point description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%. FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    97
    98
    Units: Percent change
        least squares mean (confidence interval 95%)
    -21.6 (-32.3 to -10.8)
    4 (-6.9 to 14.9)
    -26.9 (-37.5 to -16.3)
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [14]
    P-value
    		 < 0.001 [15]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    -25.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.6
         upper limit
    		 -15.6
    Notes
    [14] - Due to inadequate sample size, the secondary hypothesis was not tested. Nominal p-value is provided.
    [15] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [16]
    P-value
    		 = 0.286 [17]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    5.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.5
         upper limit
    		 15.2
    Notes
    [16] - There is no hypothesis comparing Sitagliptin/Simvastatin vs. Simvastatin for LDL-C-lowering. Nominal p-value is provided.
    [17] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.

    Secondary: Percent change from baseline in TC at Week 16

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    End point title
    		 Percent change from baseline in TC at Week 16
    End point description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%. FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    97
    98
    Units: Percent change
        least squares mean (confidence interval 95%)
    -18.4 (-26.6 to -10.2)
    -0.4 (-8.6 to 7.9)
    -18.4 (-26.4 to -10.4)
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 other [18]
    P-value
    		 < 0.001 [19]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    -18.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.2
         upper limit
    		 -12
    Notes
    [18] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Sitagliptin for TC-lowering. Nominal p-value is provided.
    [19] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [20]
    P-value
    		 = 0.99 [21]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 6
    Notes
    [20] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Simvastatin for TC-lowering. Nominal p-value is provided.
    [21] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.

    Secondary: Percent change from baseline in Apo B at Week 16

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    End point title
    		 Percent change from baseline in Apo B at Week 16
    End point description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%. FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    94
    98
    Units: Percent change
        least squares mean (confidence interval 95%)
    -16.9 (-27 to -6.8)
    3.3 (-7.1 to 13.7)
    -19.8 (-30 to -9.6)
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 other [22]
    P-value
    		 < 0.001 [23]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    -20.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.3
         upper limit
    		 -12.2
    Notes
    [22] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Sitagliptin for Apo B-lowering. Nominal p-value is provided.
    [23] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [24]
    P-value
    		 = 0.469 [25]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 10.7
    Notes
    [24] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Simvastatin for Apo B-lowering. Nominal p-value is provided.
    [25] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.

    Secondary: Percent change from baseline in non-HDL-C at Week 16

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    End point title
    		 Percent change from baseline in non-HDL-C at Week 16
    End point description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%. FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    96
    98
    Units: Percent change
        least squares mean (confidence interval 95%)
    -23.9 (-33.9 to -13.9)
    0.6 (-9.5 to 10.7)
    -24.2 (-34 to -14.4)
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other [26]
    P-value
    		 < 0.001 [27]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    -24.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.6
         upper limit
    		 -16.3
    Notes
    [26] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Sitagliptin for non-HDL-C-lowering. Nominal p-value is provided.
    [27] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [28]
    P-value
    		 = 0.937 [29]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.7
         upper limit
    		 8.3
    Notes
    [28] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Simvastatin for non-HDL-C-lowering. Nominal p-value is provided.
    [29] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.

    Secondary: Percent change from baseline in TG at Week 16

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    End point title
    		 Percent change from baseline in TG at Week 16
    End point description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%. FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    97
    98
    Units: Percent change
        least squares mean (confidence interval 95%)
    -20.4 (-51.9 to 11.1)
    -4.9 (-39.5 to 29.7)
    -10.1 (-52.1 to 31.9)
    Statistical analysis title
    		 Difference in estimated means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 other [30]
    P-value
    		 = 0.068 [31]
    Method
    		 Robust Regression
    Parameter type
    		 Difference in estimated means
    Point estimate
    -15.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.2
         upper limit
    		 1.2
    Notes
    [30] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Sitagliptin for TG-lowering. Nominal p-value is provided.
    [31] - Based on a robust regression using M-estimation with treatment, region, and a covariate for baseline triglycerides (mg/dL). Missing data were imputed by multiple imputations.
    Statistical analysis title
    		 Difference in estimated means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [32]
    P-value
    		 = 0.365 [33]
    Method
    		 Robust Regression
    Parameter type
    		 Difference in estimated means
    Point estimate
    -10.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33.6
         upper limit
    		 13
    Notes
    [32] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Simvastatin for TG-lowering. Nominal p-value is provided.
    [33] - Based on a robust regression using M-estimation with treatment, region, and a covariate for baseline triglycerides (mg/dL). Missing data were imputed by multiple imputations.

    Secondary: Percent change from baseline in HDL-C at Week 16

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    End point title
    		 Percent change from baseline in HDL-C at Week 16
    End point description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%. FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    97
    98
    Units: Percent change
        least squares mean (confidence interval 95%)
    2.5 (-2.7 to 7.8)
    2 (-3.3 to 7.4)
    2.1 (-3 to 7.3)
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 other [34]
    P-value
    		 = 0.857 [35]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 5.8
    Notes
    [34] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Sitagliptin for HDL-C-lowering. Nominal p-value is provided.
    [35] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [36]
    P-value
    		 = 0.879 [37]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 5.6
    Notes
    [36] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Simvastatin for HDL-C-lowering. Nominal p-value is provided.
    [37] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.

    Secondary: Percent change from baseline in VLDL-C at Week 16

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    End point title
    		 Percent change from baseline in VLDL-C at Week 16
    End point description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%. FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    96
    98
    Units: Percent change
        least squares mean (confidence interval 95%)
    -17.5 (-33.8 to -1.2)
    12.9 (-4.2 to 29.9)
    -2.2 (-18.9 to 14.5)
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    		 other [38]
    P-value
    		 = 0.004 [39]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    -30.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -51
         upper limit
    		 -9.7
    Notes
    [38] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Sitagliptin for VLDL-C-lowering. Nominal p-value is provided.
    [39] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.
    Statistical analysis title
    		 Difference in least squares means
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [40]
    P-value
    		 = 0.141 [41]
    Method
    		 Longitudinal Data Analysis Model
    Parameter type
    		 Difference in least squares means
    Point estimate
    -15.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.8
         upper limit
    		 5.1
    Notes
    [40] - There is no hypothesis comparing Sitagliptin/Simvastatin FDC vs. Simvastatin for VLDL-C-lowering. Nominal p-value is provided.
    [41] - Based on a longitudinal data analysis model including terms for region, treatment, time, and the interaction of time by treatment with the restriction of common mean across treatment groups at baseline.

    Secondary: Percentage of participants with A1C level <7% at Week 16

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    End point title
    		 Percentage of participants with A1C level <7% at Week 16
    End point description
    Percentage of participants achieving glycemic goal (A1C <7%) after 16 weeks of treatment. Data as observed. FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Sitagliptin/Simvastatin FDC Sitagliptin Simvastatin
    Number of subjects analysed
    100
    97
    98
    Units: Percentage of participants
        number (not applicable)
    29.9
    29.6
    17.6
    Statistical analysis title
    		 Difference in percents
    Comparison groups
    Sitagliptin/Simvastatin FDC v Sitagliptin
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 other [42]
    Method
    Parameter type
    		 Difference in percents
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.2
         upper limit
    		 12.9
    Notes
    [42] - Based on Miettinen & Nurminen method. Missing data were imputed by multiple imputations.
    Statistical analysis title
    		 Difference in percents
    Comparison groups
    Sitagliptin/Simvastatin FDC v Simvastatin
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other [43]
    Method
    Parameter type
    		 Difference in percents
    Point estimate
    12.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 24
    Notes
    [43] - Based on Miettinen & Nurminen method. Missing data were imputed by multiple imputations.

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    Up to 18 weeks
    Adverse event reporting additional description
    All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Sitagliptin/Simvastatin FDC
    Reporting group description
    		 Sitagliptin 100 mg/simvastatin 40 mg fixed dose combination (FDC) plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be uptitrated to 6 mg once daily) as rescue therapy.

    Reporting group title
    Simvastatin
    Reporting group description
    		 Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

    Reporting group title
    Sitagliptin
    Reporting group description
    		 Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: No non-serious adverse event exceeded the 5% threshold for any reporting group.
    Serious adverse events
    		 Sitagliptin/Simvastatin FDC Simvastatin Sitagliptin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 100 (1.00%)
    1 / 98 (1.02%)
    0 / 97 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 98 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 98 (0.00%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 98 (1.02%)
    0 / 97 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Sitagliptin/Simvastatin FDC Simvastatin Sitagliptin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 98 (0.00%)
    0 / 97 (0.00%)

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    12 Sep 2013
    The trial was terminated for business reasons.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The early termination of this study resulted in a smaller number of participants analyzed.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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