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    Clinical Trial Results:
    A Randomized, Phase 3, Double-blind Trial Comparing the Effect of the Addition of Tirzepatide versus Placebo in Patients with Type 2 Diabetes Inadequately Controlled on Insulin Glargine with or without Metformin

    Summary
    EudraCT number
    		 2019-000860-99
    Trial protocol
    		 SK   CZ   DE   PL   ES  
    Global end of trial date
    13 Jan 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Dec 2021
    First version publication date
    28 Dec 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I8F-MC-GPGI
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04039503
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 16998
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    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
    13 Jan 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Jan 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to placebo in participants with type 2 diabetes that are already on insulin glargine, with or without metformin. Participants will administer tirzepatide or placebo along with their previous glucose lowering medications. The study will last approximately 47 weeks and may include about 23 visits.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Aug 2019
    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
    Czechia: 94
    Country: Number of subjects enrolled
    Germany: 129
    Country: Number of subjects enrolled
    Japan: 82
    Country: Number of subjects enrolled
    Poland: 36
    Country: Number of subjects enrolled
    Puerto Rico: 12
    Country: Number of subjects enrolled
    Slovakia: 31
    Country: Number of subjects enrolled
    Spain: 57
    Country: Number of subjects enrolled
    United States: 34
    Worldwide total number of subjects
    475
    EEA total number of subjects
    347
    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)
    283
    From 65 to 84 years
    192
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 No Text Available

    Pre-assignment
    Screening details
    		 No Text Available

    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
    		 5 mg Tirzepatide
    Arm description
    		 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tirzepatide
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered SC as add-on to the pre-trial background medication.

    Arm title
    		 10 mg Tirzepatide
    Arm description
    		 10 mg tirzepatide administered SC once a week.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tirzepatide
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered SC as add-on to the pre-trial background medication.

    Arm title
    		 15 mg Tirzepatide
    Arm description
    		 15 mg tirzepatide administered SC once a week.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tirzepatide
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered SC as add-on to the pre-trial background medication.

    Arm title
    		 Placebo
    Arm description
    		 Placebo administered SC once a week.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered SC as add-on to the pre-trial background medication.

    Number of subjects in period 1
    		5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Started
    116
    119
    120
    120
    Completed
    109
    115
    110
    117
    Not completed
    7
    4
    10
    3
         Consent withdrawn by subject
    4
    3
    5
    2
         Adverse event, non-fatal
    3
    -
    2
    -
         Lost to follow-up
    -
    -
    1
    -
         Protocol deviation
    -
    1
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    5 mg Tirzepatide
    Reporting group description
    		 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

    Reporting group title
    10 mg Tirzepatide
    Reporting group description
    		 10 mg tirzepatide administered SC once a week.

    Reporting group title
    15 mg Tirzepatide
    Reporting group description
    		 15 mg tirzepatide administered SC once a week.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo administered SC once a week.

    Reporting group values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo Total
    Number of subjects
    		 116 119 120 120 475
    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 (standard deviation)
    		 61.50 ( 9.81 ) 60.40 ( 10.24 ) 60.50 ( 9.92 ) 60.00 ( 9.63 ) -
    Gender categorical
    Units: Subjects
        Female
    		 55 47 55 54 211
        Male
    		 61 72 65 66 264
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 8 5 5 22
        Not Hispanic or Latino
    		 94 95 93 98 380
        Unknown or Not Reported
    		 18 16 22 17 73
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 1 0 2
        Asian
    		 20 21 22 22 85
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 1 2 3 0 6
        White
    		 95 94 94 97 380
        More than one race
    		 0 1 0 1 2
        Unknown or Not Reported
    		 0 0 0 0 0
    Region of Enrollment
    Units: Subjects
        Czechia
    		 24 24 23 23 94
        Germany
    		 32 32 33 32 129
        Japan
    		 19 21 20 22 82
        Poland
    		 8 9 10 9 36
        Puerto Rico
    		 2 6 1 3 12
        Slovakia
    		 8 7 8 8 31
        Spain
    		 13 15 15 14 57
        United States
    		 10 5 10 9 34
    Hemoglobin A1c
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time.
    Units: Percentage of HbA1c
        arithmetic mean (standard deviation)
    		 8.30 ( 0.88 ) 8.36 ( 0.83 ) 8.23 ( 0.86 ) 8.37 ( 0.84 ) -

    End points

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    End points reporting groups
    Reporting group title
    5 mg Tirzepatide
    Reporting group description
    		 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

    Reporting group title
    10 mg Tirzepatide
    Reporting group description
    		 10 mg tirzepatide administered SC once a week.

    Reporting group title
    15 mg Tirzepatide
    Reporting group description
    		 15 mg tirzepatide administered SC once a week.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo administered SC once a week.

    Primary: Change from Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)

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    End point title
    		 Change from Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) [1]
    End point description
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). Analysis Population Description (APD): All randomized participants from who received at least 1 dose study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Primary
    End point timeframe
    Baseline, Week 40
    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: No statistical analysis planned for this outcome.
    End point values
    		 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Number of subjects analysed
    113
    117
    118
    Units: Percentage of HbA1c
        least squares mean (standard error)
    -2.59 ( 0.081 )
    -2.59 ( 0.083 )
    -0.93 ( 0.079 )
    Statistical analysis title
    		 Hemoglobin A1c (HbA1c)
    Comparison groups
    10 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    231
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.88
         upper limit
    		 -1.43
    Statistical analysis title
    		 Hemoglobin A1c (HbA1c)
    Comparison groups
    15 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.88
         upper limit
    		 -1.43

    Secondary: Change from Baseline in HbA1c (5 mg)

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    End point title
    		 Change from Baseline in HbA1c (5 mg) [2]
    End point description
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All randomized participants who received at least one dose of 5 mg tirzepatide, placebo and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 40
    Notes
    [2] - 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: No statistical analysis planned for this outcome.
    End point values
    		 5 mg Tirzepatide Placebo
    Number of subjects analysed
    115
    118
    Units: Percentage of HbA1c
        least squares mean (standard error)
    -2.23 ( 0.081 )
    -0.93 ( 0.079 )
    Statistical analysis title
    		 Hemoglobin A1c (HbA1c)
    Comparison groups
    5 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    233
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.52
         upper limit
    		 -1.07

    Secondary: Change from Baseline in Body Weight

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    End point title
    		 Change from Baseline in Body Weight
    End point description
    Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (<= 8.0%, >8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 40
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Number of subjects analysed
    115
    113
    117
    118
    Units: Kilograms (kg)
        least squares mean (standard error)
    -6.2 ( 0.58 )
    -8.2 ( 0.58 )
    -10.9 ( 0.59 )
    1.7 ( 0.57 )
    Statistical analysis title
    		 Change from Baseline in Body Weight
    Comparison groups
    5 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    233
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -7.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.4
         upper limit
    		 -6.3
    Statistical analysis title
    		 Change from Baseline in Body Weight
    Comparison groups
    10 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    231
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -9.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.5
         upper limit
    		 -8.3
    Statistical analysis title
    		 Change from Baseline in Body Weight
    Comparison groups
    15 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -12.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.2
         upper limit
    		 -11

    Secondary: Percentage of Participants Achieving an HbA1c Target Value of <7%

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    End point title
    		 Percentage of Participants Achieving an HbA1c Target Value of <7%
    End point description
    Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A.HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Week 40
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Number of subjects analysed
    115
    113
    117
    118
    Units: Percentage of Participants
        number (not applicable)
    93.04
    97.35
    94.02
    33.90
    Statistical analysis title
    		 HbA1c Target Value of <7%
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    233
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    37.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 15.23
         upper limit
    		 93.7
    Statistical analysis title
    		 HbA1c Target Value of <7%
    Comparison groups
    10 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    231
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    100.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 30.02
         upper limit
    		 333.62
    Statistical analysis title
    		 HbA1c Target Value of <7%
    Comparison groups
    15 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    43.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 16.92
         upper limit
    		 110.83

    Secondary: Change from Baseline in Fasting Serum Glucose

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    End point title
    		 Change from Baseline in Fasting Serum Glucose
    End point description
    Change from Baseline in Fasting Serum Glucose. LS Mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 40
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Number of subjects analysed
    115
    116
    118
    118
    Units: milligram per Deciliter (mg/dL)
        least squares mean (standard error)
    -61.4 ( 2.55 )
    -67.9 ( 2.55 )
    -67.7 ( 2.64 )
    -38.9 ( 2.49 )
    Statistical analysis title
    		 Change from Baseline in Fasting Serum Glucose
    Comparison groups
    5 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    233
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -22.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.5
         upper limit
    		 -15.4
    Statistical analysis title
    		 Change from Baseline in Fasting Serum Glucose
    Comparison groups
    10 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    234
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36
         upper limit
    		 -22
    Statistical analysis title
    		 Change from Baseline in Fasting Serum Glucose
    Comparison groups
    15 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    236
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -28.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.9
         upper limit
    		 -21.6

    Secondary: Mean Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

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    End point title
    		 Mean Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
    End point description
    The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (<= 8.0%, >8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment (Type III sum of squares). APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 40
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Number of subjects analysed
    100
    99
    94
    97
    Units: mg/dL
        least squares mean (standard error)
    -67.1 ( 2.05 )
    -71.7 ( 2.04 )
    -73.7 ( 2.10 )
    -39.4 ( 2.07 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Achieved Weight Loss ≥5%

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    End point title
    		 Percentage of Participants who Achieved Weight Loss ≥5%
    End point description
    Percentage of Participants who Achieved Weight Loss ≥5%. APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Week 40
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Number of subjects analysed
    115
    113
    117
    118
    Units: Percentage of Participants
        number (not applicable)
    53.91
    64.60
    84.62
    5.93
    Statistical analysis title
    		 Weight Loss ≥5%
    Comparison groups
    5 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    233
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    17.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.55
         upper limit
    		 38.93
    Statistical analysis title
    		 Weight Loss ≥5%
    Comparison groups
    10 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    231
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    27.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.87
         upper limit
    		 62.55
    Statistical analysis title
    		 Weight Loss ≥5%
    Comparison groups
    15 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    79.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 32.76
         upper limit
    		 193.44

    Secondary: Percentage Change from Baseline in Daily Mean InsulinGlargine Dose

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    End point title
    		 Percentage Change from Baseline in Daily Mean InsulinGlargine Dose
    End point description
    LS mean was calculated using MMRM model with log (Baseline) + Baseline Metformin Use (Yes, No) + Pooled Country + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 40
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Number of subjects analysed
    105
    103
    96
    111
    Units: International Units (IU)
        least squares mean (standard error)
    13.0 ( 7.34 )
    8.1 ( 7.03 )
    -11.4 ( 5.85 )
    75.0 ( 11.11 )
    Statistical analysis title
    		 Daily Mean InsulinGlargine Dose
    Comparison groups
    5 mg Tirzepatide v 10 mg Tirzepatide
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Estimate Difference
    Point estimate
    -35.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -46
         upper limit
    		 -22.8
    Statistical analysis title
    		 Daily Mean InsulinGlargine Dose
    Comparison groups
    10 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Estimate Difference
    Point estimate
    -38.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -48.3
         upper limit
    		 -26.1
    Statistical analysis title
    		 Daily Mean InsulinGlargine Dose
    Comparison groups
    15 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    207
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Estimate Difference
    Point estimate
    -49.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -57.7
         upper limit
    		 -39.4

    Secondary: Rate of Hypoglycemia with Blood Glucose <54 milligram/deciliter (mg/dL) [<3.0 millimole/liter (mmol/L)] or Severe Hypoglycemia

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    End point title
    		 Rate of Hypoglycemia with Blood Glucose <54 milligram/deciliter (mg/dL) [<3.0 millimole/liter (mmol/L)] or Severe Hypoglycemia
    End point description
    The hypoglycemia events were defined by participant reported events with blood glucose <54mg/dL) (<3.0 mmol/L] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment, with log (exposure in days/365.25) as an offset variable. APD: All randomly assigned participants who took at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline through Safety Follow-Up (Up to Week 44)
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Number of subjects analysed
    116
    119
    120
    120
    Units: Episodes/participant/365.25 days
        arithmetic mean (standard error)
    0.49 ( 0.141 )
    0.66 ( 0.169 )
    0.38 ( 0.099 )
    0.51 ( 0.149 )
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide

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    End point title
    		 Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide [3]
    End point description
    AUC is a combined measure obtained from Week 7, 15, 23 and 39 and a single averaged measure of AUC was reported. APD: All randomized participants who received at least one dose and had evaluable PK data.
    End point type
    Secondary
    End point timeframe
    Week 7, 15, 23 and 39 post dose
    Notes
    [3] - 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: No statistical analysis planned for this outcome.
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Number of subjects analysed
    115
    116
    118
    Units: nanogram*hour per milliliter (ng*h/mL)
        geometric mean (geometric coefficient of variation)
    79700 ( 24.5 )
    164000 ( 26.7 )
    246000 ( 26.4 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving an HbA1c Target Value of <5.7%

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    End point title
    		 Percentage of Participants Achieving an HbA1c Target Value of <5.7%
    End point description
    Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug
    End point type
    Secondary
    End point timeframe
    Week 40
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Number of subjects analysed
    115
    113
    117
    118
    Units: Percentage of Participants
        number (not applicable)
    26.09
    47.79
    62.39
    2.54
    Statistical analysis title
    		 HbA1c Target Value of <5.7%
    Comparison groups
    5 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    233
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    12.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.93
         upper limit
    		 38
    Statistical analysis title
    		 HbA1c Target Value of <5.7%
    Comparison groups
    10 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    231
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    32.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.52
         upper limit
    		 99.49
    Statistical analysis title
    		 HbA1c Target Value of <5.7%
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    56.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.27
         upper limit
    		 173.26

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline, 17 Months
    Adverse event reporting additional description
    All randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    TZP 5mg
    Reporting group description
    		 -

    Reporting group title
    TZP 10mg
    Reporting group description
    		 -

    Reporting group title
    TZP 15mg
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 TZP 5mg TZP 10mg TZP 15mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 116 (7.76%)
    13 / 119 (10.92%)
    9 / 120 (7.50%)
    10 / 120 (8.33%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    papillary renal cell carcinoma
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    renal neoplasm
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    transitional cell carcinoma
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    uterine cancer
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed [1]
    0 / 55 (0.00%)
    1 / 47 (2.13%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    aortic stenosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peripheral arterial occlusive disease
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    cardiac ablation
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pancreatic lesion excision
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    impaired healing
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    2 / 120 (1.67%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dyspnoea
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    respiratory failure
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sleep apnoea syndrome
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    anxiety
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    hip fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    humerus fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intestinal anastomosis complication
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal compression fracture
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    acute myocardial infarction
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    angina pectoris
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac failure
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    3 / 116 (2.59%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery disease
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    2 / 120 (1.67%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    tachycardia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    hypoglycaemic unconsciousness
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    orthostatic intolerance
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    syncope
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    deafness unilateral
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal hernia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    faecaloma
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pancreatic disorder
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    bladder disorder
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    calculus urinary
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    spinal stenosis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    synovial cyst
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    covid-19 pneumonia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronavirus infection
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 119 (0.00%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    postoperative wound infection
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    0 / 120 (0.00%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pyelonephritis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    hypoglycaemia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 119 (0.84%)
    1 / 120 (0.83%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 TZP 5mg TZP 10mg TZP 15mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    52 / 116 (44.83%)
    60 / 119 (50.42%)
    67 / 120 (55.83%)
    58 / 120 (48.33%)
    Investigations
    lipase increased
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    4 / 116 (3.45%)
    2 / 119 (1.68%)
    10 / 120 (8.33%)
    2 / 120 (1.67%)
         occurrences all number
    4
    2
    12
    2
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    3 / 116 (2.59%)
    3 / 119 (2.52%)
    1 / 120 (0.83%)
    7 / 120 (5.83%)
         occurrences all number
    3
    3
    1
    7
    Gastrointestinal disorders
    constipation
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    7 / 116 (6.03%)
    8 / 119 (6.72%)
    8 / 120 (6.67%)
    2 / 120 (1.67%)
         occurrences all number
    7
    8
    9
    2
    diarrhoea
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    14 / 116 (12.07%)
    15 / 119 (12.61%)
    25 / 120 (20.83%)
    12 / 120 (10.00%)
         occurrences all number
    22
    46
    44
    12
    dyspepsia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    8 / 116 (6.90%)
    10 / 119 (8.40%)
    6 / 120 (5.00%)
    2 / 120 (1.67%)
         occurrences all number
    9
    12
    6
    2
    eructation
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    6 / 116 (5.17%)
    4 / 119 (3.36%)
    7 / 120 (5.83%)
    1 / 120 (0.83%)
         occurrences all number
    11
    16
    11
    1
    flatulence
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    3 / 116 (2.59%)
    6 / 119 (5.04%)
    7 / 120 (5.83%)
    0 / 120 (0.00%)
         occurrences all number
    3
    21
    12
    0
    nausea
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    15 / 116 (12.93%)
    21 / 119 (17.65%)
    22 / 120 (18.33%)
    3 / 120 (2.50%)
         occurrences all number
    26
    43
    44
    3
    vomiting
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    8 / 116 (6.90%)
    9 / 119 (7.56%)
    15 / 120 (12.50%)
    3 / 120 (2.50%)
         occurrences all number
    12
    18
    26
    3
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    6 / 116 (5.17%)
    4 / 119 (3.36%)
    3 / 120 (2.50%)
    2 / 120 (1.67%)
         occurrences all number
    7
    4
    3
    2
    back pain
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    6 / 116 (5.17%)
    6 / 119 (5.04%)
    4 / 120 (3.33%)
    7 / 120 (5.83%)
         occurrences all number
    8
    7
    6
    7
    Infections and infestations
    nasopharyngitis
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    18 / 116 (15.52%)
    8 / 119 (6.72%)
    15 / 120 (12.50%)
    23 / 120 (19.17%)
         occurrences all number
    23
    11
    19
    27
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    8 / 116 (6.90%)
    15 / 119 (12.61%)
    17 / 120 (14.17%)
    2 / 120 (1.67%)
         occurrences all number
    8
    17
    21
    2
    hyperglycaemia
    alternative dictionary used: MedDRA 23.1
         subjects affected / exposed
    2 / 116 (1.72%)
    0 / 119 (0.00%)
    1 / 120 (0.83%)
    16 / 120 (13.33%)
         occurrences all number
    2
    0
    1
    18

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Jun 2020
    Protocol (b): Added language about the mobile (inhome) healthcare visits.

    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
    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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