Clincosm LogoSign in Get a demo

A Long-term Safety Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT03861039
Collaborator
(none)
443
Enrollment
34
Locations
3
Arms
22.6
Actual Duration (Months)
13
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the long-term safety of the study drug tirzepatide in combination with oral antihyperglycemic medications in participants with type 2 diabetes.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
443 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Long-Term Safety Study of Tirzepatide in Combination With Monotherapy of Oral Antihyperglycemic Medications in Patients With Type 2 Diabetes Mellitus (SURPASS J-combo)
Actual Study Start Date :
Mar 30, 2019
Actual Primary Completion Date :
Jan 26, 2021
Actual Study Completion Date :
Feb 16, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: 5 mg Tirzepatide

5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.

Drug: Tirzepatide
Administered SC
Other Names:
  • LY3298176

    • Drug: Oral antihyperglycemic medication (OAM)
    Oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Experimental: 10 mg Tirzepatide

    10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.

    Drug: Tirzepatide
    Administered SC
    Other Names:
  • LY3298176

    • Drug: Oral antihyperglycemic medication (OAM)
    Oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Experimental: 15 mg Tirzepatide

    15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.

    Drug: Tirzepatide
    Administered SC
    Other Names:
  • LY3298176

    • Drug: Oral antihyperglycemic medication (OAM)
    Oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [Baseline through Week 52]

      An SAE is any AE from this study that results in one of the following outcomes: Death Initial or prolonged inpatient hospitalization A life-threatening experience (that is, immediate risk of dying) Persistent or significant disability/incapacity Congenital anomaly/birth defect. Important medical events that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the patient or may require. A summary of all SAE's, regardless of causality, is located in the Reported Adverse Events section.

    Secondary Outcome Measures

    1. Change From Baseline in Hemoglobin A1c (HbA1c) [Baseline, Week 52]

      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 for post-baseline measures: Variable = Baseline + oral antihyperglycemic medication (OAM) Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    2. Percentage of Participants Who Achieve HbA1c <7% [Week 52]

      Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

    3. Change From Baseline in Fasting Serum Glucose [Baseline, Week 52]

      Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    4. Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values [Baseline, Week 52]

      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. LS mean was determined by analysis of covariance (ANCOVA) model for endpoint measures: Variable = Baseline + OAM Group 1 + Treatment (Type III sum of squares).

    5. Change From Baseline in Body Weight [Baseline, Week 52]

      LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    6. Percentage of Participants Who Achieve Weight Loss of ≥5% From Baseline [Week 52]

      Percentage of Participants who Achieve Weight Loss of ≥5% from Baseline

    7. Change From Baseline in Fasting Insulin [Baseline, Week 52]

      LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    8. Change From Baseline in Fasting C-Peptide [Baseline, Week 52]

      LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    9. Change From Baseline in Homeostasis Model Assessment B (HOMA-2B) (Insulin) [Baseline, Week 52]

      The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S). LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    10. Change From Baseline in HOMA-2S (Insulin) [Baseline, Week 52]

      The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S). LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    11. Number of Participants With Hypoglycemia Incidence and Rate With Blood Glucose <54 mg/dL or Severe Hypoglycemia, Exclude Hypoglycemic Events Occurring After Initiation of a New Antihyperglycemic Therapy [Baseline through Week 56]

      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.

    12. Number of Participants With Anti-Tirzepatide Antibodies [Baseline through Week 52]

      Number of Participants with Anti-Tirzepatide Antibodies

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    Participant must:

    • Have been diagnosed with type 2 diabetes mellitus based on the World Health Organization classification before the screening visit.

    • Have HbA1c ≥7.0% to <11.0%, as determined by the central laboratory at screening.

    • Have been taking sulfonylureas, biguanides, thiazolidinedione, alpha-glucosidase inhibitor, glinides, or sodium-glucose cotransporter type 2 inhibitor monotherapy for at least 3 months before screening and have been on the following dose for at least 8 weeks before screening.

    • Have body mass index (BMI) of ≥23 kilograms per meter squared at screening.

    • Be of stable weight (±5%) during 3 months preceding screening; and agree to not initiate an intensive diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment.

    Exclusion Criteria:
    Participant must not:

    • Have type 1 diabetes mellitus.

    • Have had chronic or acute pancreatitis any time prior to study entry.

    • Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring immediate or urgent treatment.

    • Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss.

    • Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level >3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if there ALT level is ≤3.0 the ULN for the reference range.

    • Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months.

    • Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2.

    • Have been taking weight loss drugs, including over-the-counter medications during the last 3 months.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Akaicho Clinic Chiba-shi Chiba Japan 260 0804
    2 Kashiwa hospital Kashiwa Chiba Japan 277-0825
    3 Yuri Ono Clinic Sapporo Hokkaido Japan 060-0001
    4 Manda Hospital Sapporo Hokkaido Japan 060-0062
    5 Miyanomori Hospital Sapporo Hokkaido Japan 064-8570
    6 Ikeda Hospital Amagasaki Hyogo Japan 661-0002
    7 Nakamoto Naika Clinic Mito Ibaraki Japan 310 0826
    8 Naka Memorial Clinic Naka Ibaraki Japan 311-0113
    9 Ohishi Naika Clinic Tsuchiura Ibaraki Japan 300-0835
    10 Takai Naika Clinic Kamakura Kanagawa Japan 247-0056
    11 Tsuruma Kaneshiro Diabetes Clinic Yamato Kanagawa Japan 242-0004
    12 Yokohama Minoru Clinic Yokohama Kanagawa Japan 232-0064
    13 H.E.C. Science Clinic Yokohama Kanagawa Japan 235-0045
    14 Takatsuki Red Cross Hospital Takatsuki Osaka Japan 569-1096
    15 Otsu City Hospital Otsu Shiga Japan 520-0804
    16 Wakakusa Clinic Shimotsuke Tochigi Japan 329-0433
    17 Seiwa Clinic Adachi-ku Tokyo Japan 123 0845
    18 HDC Atlas Clinic Chiyoda Tokyo Japan 102-0082
    19 Asahi Life Foundation Adult Disease Research Center Chuo-ku Tokyo Japan 103 0002
    20 Nihonbashi Sakura Clinic Chuo-ku Tokyo Japan 103-0025
    21 Tokyo-Eki Center-building Clinic Chuo-ku Tokyo Japan 103-0027
    22 Tokyo Center Clinic Chuo-ku Tokyo Japan 103-0028
    23 Tokyo Clinical Trial Centre Fukuwa Clinic Chuo-ku Tokyo Japan 104-0031
    24 Kanno Naika Mitaka Tokyo Japan 181 0013
    25 Shinjuku Research Park Clinic Shinjuku-Ku Tokyo Japan 169-0073
    26 Futata Tetsuhiro Clinic Fukuoka Japan 819 0006
    27 Morinaga Ueno Clinic Kumamoto Japan 860 0863
    28 Jinnouchi Hospital Kumamoto Japan 862-0976
    29 Abe Diabetes Clinic Oita Japan 870-0039
    30 Saiseikai Noe Hospital Osaka Japan 536 0001
    31 Kitada Clinic Osaka Japan 538 0044
    32 Kansai Denryoku Hospital Osaka Japan 553-0003
    33 Shizuoka City Shizuoka Hospital Shizuoka Japan 420-8630
    34 Suruga Clinic Shizuoka Japan 424-0855

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT03861039
    Other Study ID Numbers:
    • 17078
    • I8F-JE-GPGP
    First Posted:
    Mar 4, 2019
    Last Update Posted:
    Feb 14, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Tirzepatide
    Hypoglycemic Agents

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Period Title: Overall Study
    STARTED 148 147 148
    Received at Least One Dose of Study Drug 148 147 148
    COMPLETED 145 139 133
    NOT COMPLETED 3 8 15

    Baseline Characteristics

    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Total
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. Total of all reporting groups
    Overall Participants 148 147 148 443
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.7
    (11.0)
    56.9
    (11.2)
    56.5
    (10.4)
    57.0
    (10.8)
    Sex: Female, Male (Count of Participants)
    Female
    29
    19.6%
    34
    23.1%
    44
    29.7%
    107
    24.2%
    Male
    119
    80.4%
    113
    76.9%
    104
    70.3%
    336
    75.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    148
    100%
    147
    100%
    148
    100%
    443
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    148
    100%
    147
    100%
    148
    100%
    443
    100%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    Japan
    148
    100%
    147
    100%
    148
    100%
    443
    100%
    Hemoglobin A1c (: Percentage of HbA1c) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [: Percentage of HbA1c]
    8.53
    (1.15)
    8.56
    (1.05)
    8.59
    (1.09)
    8.56
    (1.09)

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
    Description An SAE is any AE from this study that results in one of the following outcomes: Death Initial or prolonged inpatient hospitalization A life-threatening experience (that is, immediate risk of dying) Persistent or significant disability/incapacity Congenital anomaly/birth defect. Important medical events that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the patient or may require. A summary of all SAE's, regardless of causality, is located in the Reported Adverse Events section.
    Time Frame Baseline through Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week.Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 148 147 148
    Count of Participants [Participants]
    0
    0%
    1
    0.7%
    1
    0.7%
    2. Secondary Outcome
    Title Change From Baseline in Hemoglobin A1c (HbA1c)
    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 for post-baseline measures: Variable = Baseline + oral antihyperglycemic medication (OAM) Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week.Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 148 146 145
    Least Squares Mean (Standard Error) [Percentage of HbA1c]
    -2.57
    (0.075)
    -2.98
    (0.075)
    -3.02
    (0.077)
    3. Secondary Outcome
    Title Percentage of Participants Who Achieve HbA1c <7%
    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.
    Time Frame Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 148 146 145
    Number [percentage of participants]
    92.57
    62.5%
    97.95
    66.6%
    96.55
    65.2%
    4. Secondary Outcome
    Title Change From Baseline in Fasting Serum Glucose
    Description Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 148 146 145
    Least Squares Mean (Standard Error) [milligram per Deciliter (mg/dL)]
    -58.6
    (1.75)
    -71.2
    (1.75)
    -74.4
    (1.81)
    5. Secondary Outcome
    Title Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
    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. LS mean was determined by analysis of covariance (ANCOVA) model for endpoint measures: Variable = Baseline + OAM Group 1 + Treatment (Type III sum of squares).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 136 135 125
    Least Squares Mean (Standard Error) [mg/dL]
    -80.0
    (1.91)
    -94.1
    (1.92)
    -96.3
    (1.99)
    6. Secondary Outcome
    Title Change From Baseline in Body Weight
    Description LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 148 146 145
    Least Squares Mean (Standard Error) [Kilograms (kg)]
    -3.8
    (0.51)
    -7.5
    (0.51)
    -10.2
    (0.52)
    7. Secondary Outcome
    Title Percentage of Participants Who Achieve Weight Loss of ≥5% From Baseline
    Description Percentage of Participants who Achieve Weight Loss of ≥5% from Baseline
    Time Frame Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 148 146 145
    Number [percentage of participants]
    43.92
    29.7%
    70.55
    48%
    84.14
    56.9%
    8. Secondary Outcome
    Title Change From Baseline in Fasting Insulin
    Description LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week.Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 143 144 134
    Least Squares Mean (Standard Error) [picomol per liter (pmol/L)]
    6.2
    (2.68)
    -4.8
    (2.21)
    -7.7
    (2.16)
    9. Secondary Outcome
    Title Change From Baseline in Fasting C-Peptide
    Description LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week.Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 143 144 134
    Least Squares Mean (Standard Error) [micrograms/litre (ug/L)]
    -0.12
    (0.044)
    -0.28
    (0.040)
    -0.34
    (0.040)
    10. Secondary Outcome
    Title Change From Baseline in Homeostasis Model Assessment B (HOMA-2B) (Insulin)
    Description The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S). LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 139 135 128
    Least Squares Mean (Standard Error) [percentage of HOMA-2B]
    39.7
    (2.16)
    44.9
    (2.40)
    49.2
    (2.60)
    11. Secondary Outcome
    Title Change From Baseline in HOMA-2S (Insulin)
    Description The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S). LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 139 135 128
    Least Squares Mean (Standard Error) [Percentage of HOMA-2S]
    -0.1
    (3.37)
    16.7
    (4.23)
    24.1
    (4.66)
    12. Secondary Outcome
    Title Number of Participants With Hypoglycemia Incidence and Rate With Blood Glucose <54 mg/dL or Severe Hypoglycemia, Exclude Hypoglycemic Events Occurring After Initiation of a New Antihyperglycemic Therapy
    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.
    Time Frame Baseline through Week 56

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week.Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week.Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 148 147 148
    Count of Participants [Participants]
    1
    0.7%
    1
    0.7%
    3
    2%
    13. Secondary Outcome
    Title Number of Participants With Anti-Tirzepatide Antibodies
    Description Number of Participants with Anti-Tirzepatide Antibodies
    Time Frame Baseline through Week 52

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    Measure Participants 148 147 148
    Count of Participants [Participants]
    87
    58.8%
    82
    55.8%
    88
    59.5%

    Adverse Events

    Time Frame Baseline through Week 56
    Adverse Event Reporting 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.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor. 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
    All Cause Mortality
    5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/148 (0%) 0/147 (0%) 0/148 (0%)
    Serious Adverse Events
    5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/148 (1.4%) 11/147 (7.5%) 11/148 (7.4%)
    Cardiac disorders
    Angina pectoris 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Atrioventricular block complete 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Ear and labyrinth disorders
    Vertigo positional 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Eye disorders
    Cataract 0/148 (0%) 0 2/147 (1.4%) 2 1/148 (0.7%) 1
    Eyelid ptosis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Macular fibrosis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Gastrointestinal disorders
    Colitis ulcerative 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Hepatobiliary disorders
    Cholelithiasis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Infections and infestations
    Appendicitis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Diabetic gangrene 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Pneumonia legionella 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Injury, poisoning and procedural complications
    Clavicle fracture 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Radius fracture 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Musculoskeletal and connective tissue disorders
    Joint contracture 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Spinal ligament ossification 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Bladder cancer 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Bladder papilloma 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Colon cancer 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Renal neoplasm 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Nervous system disorders
    Facial paralysis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Renal and urinary disorders
    Nephrolithiasis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Ureterolithiasis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Surgical and medical procedures
    Coronary artery bypass 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Intra-cerebral aneurysm operation 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Other (Not Including Serious) Adverse Events
    5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 109/148 (73.6%) 108/147 (73.5%) 124/148 (83.8%)
    Blood and lymphatic system disorders
    Anaemia 0/148 (0%) 0 1/147 (0.7%) 1 2/148 (1.4%) 2
    Leukopenia 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Cardiac disorders
    Angina pectoris 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Atrial fibrillation 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Atrioventricular block complete 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Bundle branch block right 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Palpitations 0/148 (0%) 0 1/147 (0.7%) 1 2/148 (1.4%) 2
    Tachycardia 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Ventricular extrasystoles 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Ventricular tachycardia 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Ear and labyrinth disorders
    Deafness neurosensory 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Meniere's disease 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Vertigo 2/148 (1.4%) 2 3/147 (2%) 3 1/148 (0.7%) 1
    Eye disorders
    Blepharitis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Cataract 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Conjunctival haemorrhage 1/148 (0.7%) 1 0/147 (0%) 0 2/148 (1.4%) 2
    Conjunctivitis allergic 0/148 (0%) 0 0/147 (0%) 0 2/148 (1.4%) 2
    Corneal leukoma 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Diabetic retinopathy 0/148 (0%) 0 3/147 (2%) 3 1/148 (0.7%) 1
    Dry eye 2/148 (1.4%) 2 0/147 (0%) 0 0/148 (0%) 0
    Eczema eyelids 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Glaucoma 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Iridocyclitis 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Maculopathy 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 2
    Ocular hypertension 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Swelling of eyelid 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Vitreous floaters 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Gastrointestinal disorders
    Abdominal discomfort 9/148 (6.1%) 10 7/147 (4.8%) 9 8/148 (5.4%) 10
    Abdominal distension 5/148 (3.4%) 6 6/147 (4.1%) 7 6/148 (4.1%) 7
    Abdominal pain 1/148 (0.7%) 1 2/147 (1.4%) 3 2/148 (1.4%) 2
    Abdominal pain upper 2/148 (1.4%) 3 4/147 (2.7%) 4 5/148 (3.4%) 5
    Anal fissure 1/148 (0.7%) 1 1/147 (0.7%) 1 1/148 (0.7%) 1
    Anal pruritus 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Aphthous ulcer 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Barrett's oesophagus 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Chronic gastritis 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Constipation 12/148 (8.1%) 12 20/147 (13.6%) 21 22/148 (14.9%) 24
    Dental caries 3/148 (2%) 3 1/147 (0.7%) 2 0/148 (0%) 0
    Diarrhoea 11/148 (7.4%) 24 20/147 (13.6%) 40 20/148 (13.5%) 28
    Dry mouth 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Dyspepsia 6/148 (4.1%) 6 11/147 (7.5%) 19 5/148 (3.4%) 6
    Enterocolitis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Eructation 0/148 (0%) 0 2/147 (1.4%) 2 1/148 (0.7%) 1
    Faeces soft 1/148 (0.7%) 1 2/147 (1.4%) 2 3/148 (2%) 3
    Flatulence 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Functional gastrointestinal disorder 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Gastric disorder 2/148 (1.4%) 2 0/147 (0%) 0 0/148 (0%) 0
    Gastric ulcer 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Gastritis 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Gastritis erosive 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Gastrointestinal disorder 1/148 (0.7%) 1 0/147 (0%) 0 4/148 (2.7%) 4
    Gastrooesophageal reflux disease 4/148 (2.7%) 4 6/147 (4.1%) 6 4/148 (2.7%) 4
    Haematochezia 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Haemorrhoids 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Hiatus hernia 1/148 (0.7%) 1 1/147 (0.7%) 1 0/148 (0%) 0
    Inguinal hernia 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Irritable bowel syndrome 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Large intestine polyp 2/148 (1.4%) 2 1/147 (0.7%) 1 0/148 (0%) 0
    Nausea 14/148 (9.5%) 60 20/147 (13.6%) 35 40/148 (27%) 51
    Oesophagitis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Parotid gland enlargement 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Stomatitis 2/148 (1.4%) 2 0/147 (0%) 0 1/148 (0.7%) 1
    Toothache 1/148 (0.7%) 1 1/147 (0.7%) 1 1/148 (0.7%) 1
    Vomiting 4/148 (2.7%) 5 11/147 (7.5%) 13 15/148 (10.1%) 23
    General disorders
    Asthenia 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Chest discomfort 1/148 (0.7%) 4 0/147 (0%) 0 0/148 (0%) 0
    Chest pain 1/148 (0.7%) 1 0/147 (0%) 0 2/148 (1.4%) 4
    Fatigue 2/148 (1.4%) 2 2/147 (1.4%) 2 3/148 (2%) 4
    Injection site haemorrhage 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Injection site pain 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 2
    Injection site reaction 4/148 (2.7%) 7 3/147 (2%) 25 4/148 (2.7%) 72
    Malaise 2/148 (1.4%) 2 3/147 (2%) 4 6/148 (4.1%) 6
    Oedema peripheral 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Pyrexia 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Hepatobiliary disorders
    Cholelithiasis 1/148 (0.7%) 1 1/147 (0.7%) 1 1/148 (0.7%) 1
    Fatty liver alcoholic 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Gallbladder polyp 1/148 (0.7%) 1 0/147 (0%) 0 2/148 (1.4%) 2
    Hepatic cyst 0/148 (0%) 0 1/147 (0.7%) 1 2/148 (1.4%) 2
    Hepatic function abnormal 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Hepatic steatosis 1/148 (0.7%) 1 1/147 (0.7%) 1 0/148 (0%) 0
    Hepatomegaly 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Immune system disorders
    Seasonal allergy 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Infections and infestations
    Acute sinusitis 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Adenoviral conjunctivitis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Bronchitis 2/148 (1.4%) 2 0/147 (0%) 0 0/148 (0%) 0
    Campylobacter gastroenteritis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Cellulitis 1/148 (0.7%) 1 1/147 (0.7%) 1 0/148 (0%) 0
    Conjunctivitis 1/148 (0.7%) 1 1/147 (0.7%) 1 1/148 (0.7%) 1
    Cystitis 0/148 (0%) 0 3/147 (2%) 3 2/148 (1.4%) 6
    Dermatitis infected 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Empyema 0/148 (0%) 0 2/147 (1.4%) 2 0/148 (0%) 0
    Enterocolitis viral 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Folliculitis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Furuncle 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Gastroenteritis 7/148 (4.7%) 9 5/147 (3.4%) 5 4/148 (2.7%) 4
    Gastroenteritis viral 2/148 (1.4%) 2 1/147 (0.7%) 1 1/148 (0.7%) 1
    Gingivitis 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Helicobacter infection 2/148 (1.4%) 2 1/147 (0.7%) 1 0/148 (0%) 0
    Hepatitis e 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Herpes simplex 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Herpes virus infection 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Herpes zoster 1/148 (0.7%) 1 4/147 (2.7%) 4 3/148 (2%) 3
    Hordeolum 1/148 (0.7%) 1 0/147 (0%) 0 2/148 (1.4%) 3
    Infected dermal cyst 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Influenza 5/148 (3.4%) 5 1/147 (0.7%) 1 2/148 (1.4%) 2
    Nasal vestibulitis 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Nasopharyngitis 28/148 (18.9%) 34 20/147 (13.6%) 26 27/148 (18.2%) 37
    Oral herpes 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Otitis media 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Paronychia 1/148 (0.7%) 1 1/147 (0.7%) 1 1/148 (0.7%) 1
    Parotitis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Periodontitis 1/148 (0.7%) 1 1/147 (0.7%) 1 2/148 (1.4%) 2
    Pharyngitis 1/148 (0.7%) 1 3/147 (2%) 3 2/148 (1.4%) 2
    Rhinitis 3/148 (2%) 4 0/147 (0%) 0 1/148 (0.7%) 1
    Sinusitis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Tinea pedis 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Tonsillitis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Tracheobronchitis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Upper respiratory tract infection 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Varicella 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Vulvovaginal candidiasis 0/29 (0%) 0 2/34 (5.9%) 2 1/44 (2.3%) 1
    Injury, poisoning and procedural complications
    Animal bite 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Ankle fracture 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Arthropod sting 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Compression fracture 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Contusion 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Epicondylitis 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Foot fracture 0/148 (0%) 0 3/147 (2%) 3 0/148 (0%) 0
    Heat illness 1/148 (0.7%) 1 1/147 (0.7%) 1 0/148 (0%) 0
    Ligament sprain 2/148 (1.4%) 3 2/147 (1.4%) 3 1/148 (0.7%) 1
    Post-traumatic neck syndrome 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Procedural pain 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Radius fracture 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Rib fracture 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Skin abrasion 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Skin laceration 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Spinal compression fracture 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Thermal burn 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Upper limb fracture 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Wound 0/148 (0%) 0 3/147 (2%) 3 0/148 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/148 (0%) 0 0/147 (0%) 0 2/148 (1.4%) 2
    Amylase increased 2/148 (1.4%) 3 3/147 (2%) 3 2/148 (1.4%) 2
    Aspartate aminotransferase increased 0/148 (0%) 0 0/147 (0%) 0 3/148 (2%) 3
    Blood alkaline phosphatase increased 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Blood calcitonin increased 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Blood creatine phosphokinase increased 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Blood creatinine increased 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Blood pressure decreased 2/148 (1.4%) 3 1/147 (0.7%) 1 1/148 (0.7%) 1
    Electrocardiogram st segment depression 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Gamma-glutamyltransferase increased 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Heart rate increased 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Helicobacter test positive 1/148 (0.7%) 1 1/147 (0.7%) 1 0/148 (0%) 0
    Hepatic enzyme increased 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 3
    Lipase increased 4/148 (2.7%) 5 4/147 (2.7%) 4 9/148 (6.1%) 9
    Occult blood 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Occult blood positive 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Salmonella test positive 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Urine albumin/creatinine ratio increased 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Weight decreased 1/148 (0.7%) 1 8/147 (5.4%) 8 6/148 (4.1%) 6
    Metabolism and nutrition disorders
    Decreased appetite 11/148 (7.4%) 11 15/147 (10.2%) 18 18/148 (12.2%) 19
    Dehydration 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Gout 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Hyperamylasaemia 1/148 (0.7%) 2 1/147 (0.7%) 1 0/148 (0%) 0
    Hypercalcitoninaemia 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Hyperglycaemia 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Hyperlipasaemia 1/148 (0.7%) 2 1/147 (0.7%) 1 1/148 (0.7%) 1
    Hyperlipidaemia 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Hyperuricaemia 1/148 (0.7%) 1 1/147 (0.7%) 1 1/148 (0.7%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/148 (1.4%) 2 2/147 (1.4%) 2 4/148 (2.7%) 4
    Arthritis 1/148 (0.7%) 1 1/147 (0.7%) 1 1/148 (0.7%) 1
    Back pain 4/148 (2.7%) 4 8/147 (5.4%) 8 0/148 (0%) 0
    Coccydynia 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Intervertebral disc protrusion 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Lumbar spinal stenosis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Muscle spasms 0/148 (0%) 0 1/147 (0.7%) 2 1/148 (0.7%) 1
    Musculoskeletal stiffness 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Myalgia 2/148 (1.4%) 2 1/147 (0.7%) 1 0/148 (0%) 0
    Myositis 1/148 (0.7%) 1 1/147 (0.7%) 1 0/148 (0%) 0
    Neck pain 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Nodal osteoarthritis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Osteoarthritis 0/148 (0%) 0 1/147 (0.7%) 1 2/148 (1.4%) 2
    Osteoporosis 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Pain in extremity 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Periarthritis 2/148 (1.4%) 2 2/147 (1.4%) 2 2/148 (1.4%) 2
    Rotator cuff syndrome 0/148 (0%) 0 2/147 (1.4%) 2 0/148 (0%) 0
    Spinal osteoarthritis 2/148 (1.4%) 2 0/147 (0%) 0 0/148 (0%) 0
    Spinal stenosis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Synovial cyst 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Tendon pain 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Tenosynovitis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Tenosynovitis stenosans 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Trigger finger 0/148 (0%) 0 2/147 (1.4%) 2 0/148 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm skin 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Renal neoplasm 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Skin papilloma 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Uterine leiomyoma 0/29 (0%) 0 0/34 (0%) 0 1/44 (2.3%) 1
    Nervous system disorders
    Autonomic nervous system imbalance 0/148 (0%) 0 1/147 (0.7%) 3 0/148 (0%) 0
    Cervical radiculopathy 0/148 (0%) 0 1/147 (0.7%) 2 0/148 (0%) 0
    Dizziness 1/148 (0.7%) 1 2/147 (1.4%) 2 8/148 (5.4%) 8
    Dizziness postural 0/148 (0%) 0 3/147 (2%) 6 0/148 (0%) 0
    Dysaesthesia 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Dysgeusia 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Facial paralysis 0/148 (0%) 0 0/147 (0%) 0 2/148 (1.4%) 2
    Headache 4/148 (2.7%) 4 4/147 (2.7%) 4 4/148 (2.7%) 4
    Hypoaesthesia 3/148 (2%) 4 0/147 (0%) 0 0/148 (0%) 0
    Intercostal neuralgia 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Somnolence 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Syncope 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Tremor 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Trigeminal neuralgia 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Psychiatric disorders
    Adjustment disorder with depressed mood 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Depression 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Panic disorder 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Renal and urinary disorders
    Calculus urinary 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Diabetic nephropathy 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Haematuria 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Hydronephrosis 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Nephrocalcinosis 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Nephrolithiasis 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Pollakiuria 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Renal cyst 2/148 (1.4%) 2 1/147 (0.7%) 1 4/148 (2.7%) 4
    Renal impairment 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1
    Ureterolithiasis 0/148 (0%) 0 0/147 (0%) 0 2/148 (1.4%) 3
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/119 (0%) 0 1/113 (0.9%) 1 0/104 (0%) 0
    Breast calcifications 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Menorrhagia 0/29 (0%) 0 1/34 (2.9%) 1 0/44 (0%) 0
    Vulvovaginal inflammation 0/29 (0%) 0 1/34 (2.9%) 1 0/44 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Cough 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Cystic lung disease 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Dysphonia 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Dyspnoea 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Epistaxis 0/148 (0%) 0 1/147 (0.7%) 1 1/148 (0.7%) 1
    Hiccups 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 2
    Oropharyngeal discomfort 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Oropharyngeal pain 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Rhinitis allergic 0/148 (0%) 0 0/147 (0%) 0 2/148 (1.4%) 2
    Rhinorrhoea 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Upper respiratory tract inflammation 1/148 (0.7%) 1 1/147 (0.7%) 2 0/148 (0%) 0
    Skin and subcutaneous tissue disorders
    Asteatosis 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Decubitus ulcer 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Dermal cyst 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Dermatitis 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Dermatitis contact 0/148 (0%) 0 1/147 (0.7%) 2 0/148 (0%) 0
    Drug eruption 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Dry skin 1/148 (0.7%) 1 0/147 (0%) 0 4/148 (2.7%) 4
    Dyshidrotic eczema 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Eczema 4/148 (2.7%) 4 1/147 (0.7%) 1 3/148 (2%) 3
    Eczema asteatotic 2/148 (1.4%) 2 1/147 (0.7%) 1 1/148 (0.7%) 1
    Haemorrhage subcutaneous 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Ingrowing nail 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Miliaria 1/148 (0.7%) 1 0/147 (0%) 0 0/148 (0%) 0
    Pain of skin 0/148 (0%) 0 1/147 (0.7%) 1 0/148 (0%) 0
    Pruritus 0/148 (0%) 0 2/147 (1.4%) 2 1/148 (0.7%) 1
    Psoriasis 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Rash 1/148 (0.7%) 1 1/147 (0.7%) 1 1/148 (0.7%) 1
    Urticaria 2/148 (1.4%) 2 1/147 (0.7%) 1 1/148 (0.7%) 1
    Surgical and medical procedures
    Cataract operation 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Intraocular lens implant 0/148 (0%) 0 1/147 (0.7%) 2 0/148 (0%) 0
    Skin lesion removal 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Transurethral bladder resection 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Ureteric calculus removal 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Urethral stent insertion 0/148 (0%) 0 0/147 (0%) 0 1/148 (0.7%) 1
    Vascular disorders
    Arteriosclerosis 2/148 (1.4%) 2 1/147 (0.7%) 1 0/148 (0%) 0
    Hypertension 3/148 (2%) 3 1/147 (0.7%) 1 1/148 (0.7%) 1
    Orthostatic hypotension 1/148 (0.7%) 1 0/147 (0%) 0 1/148 (0.7%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email ClinicalTrials.gov@lilly.com
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT03861039
    Other Study ID Numbers:
    • 17078
    • I8F-JE-GPGP
    First Posted:
    Mar 4, 2019
    Last Update Posted:
    Feb 14, 2022
    Last Verified:
    Jan 1, 2022