A Study of Tirzepatide (LY3298176) Compared to Dulaglutide in Participants With Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— SURPASS J-mono  

Official title:

A Phase 3 Study of Tirzepatide Monotherapy Compared to Dulaglutide 0.75 mg in Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03861052
• Other study ID #: 17077
• Secondary ID: I8F-JE-GPGO
• Status: Completed
• Phase: Phase 3
• Start date: May 7, 2019
• Est. completion date: March 31, 2021

Study information

• Verified date: April 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The reason for this study is to see if the study drug tirzepatide (LY3298176) is effective and safe compared to dulaglutide in participants with type 2 diabetes in Japan.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 636
• Est. completion date: March 31, 2021
• Est. primary completion date: March 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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 meeting the following criteria, as determined by the central laboratory at

screening and baseline:

• for participants who are oral antihyperglycemic medication (OAM)-naïve at screening, =7.0% to =10.0% at both screening and baseline.
• for participants who have been taking OAM monotherapy at screening, =6.5% to =9.0% at screening, and =7.0% to =10.0% at baseline.
• 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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Tirzepatide
Administered SC
• Dulaglutide
Administered SC

Locations

Country	Name	City	State
Japan	Seiwa Clinic	Adachi-ku	Tokyo
Japan	Medical corporation THY Tokuyama Clinic	Chiba Mihama-ku	Chiba
Japan	Akaicho Clinic	Chiba-shi	Chiba
Japan	Hayashi Diabetes Internal Medicine Clinic	Chigasaki-sh	Kanagawa
Japan	Hasegawa Medical Clinic	Chitose	Hokkaido
Japan	HDC Atlas Clinic	Chiyoda	Tokyo
Japan	Meiwa Hospital	Chiyodaku	Tokyo
Japan	Asahi Life Foundation Adult Disease Research Center	Chuo-ku	Tokyo
Japan	Fukuwa Clinic	Chuo-ku	Tokyo
Japan	Medical Corporation Chiseikai Tokyo Center Clinic	Chuo-ku	Tokyo
Japan	Nihonbashi Sakura Clinic	Chuo-ku	Tokyo
Japan	Tokyo aSBo Clinic	Chuo-ku	Tokyo
Japan	Tokyo-Eki Center-building Clinic	Chuo-ku	Tokyo
Japan	Matoba Diabetes Clinic	Ebina	Kanagawa
Japan	Futata Tetsuhiro Clinic	Fukuoka
Japan	JR Hiroshima Hospital	Hiroshima
Japan	Takai Naika Clinic	Kamakura	Kanagawa
Japan	Asano Clinic	Kawagoe	Saitama
Japan	Kawaguchi General Hospital	Kawaguchi	Saitama
Japan	Kanto Rosai Hospital	Kawasaki	Kanagawa
Japan	Yoshimura Clinic	Kumamoto
Japan	National Hospital Organization Kure Medical Center	Kure	Hiroshima
Japan	Keiseikai Kajiyama Clinic	Kyoto
Japan	IHL Shinagawa East One Medical Clinic	Minato-ku	Tokyo
Japan	Naka Memorial Clinic	Naka	Ibaraki
Japan	Hayashi Clinic	Nishinomiya	Hyogo
Japan	Watanabe Naika Clinic	Nishinomiya	Hyogo
Japan	Abe Clinic	Oita
Japan	OKAYAMA Medical Center	Okayama
Japan	Sato Medical Clinic	Ootaku	Tokyo
Japan	AMC Nishiumeda Clinic	Osaka
Japan	Kitada Clinic	Osaka
Japan	Nanko Clinic	Osaka
Japan	Yuri Ono Clinic	Sapporo	Hokkaido
Japan	Wakakusa Clinic	Shimotsuke	Tochigi
Japan	Shinjuku Research Park Clinic	Shinjuku	Tokyo
Japan	Medical Corporation Heishinkai ToCROM Clinic	Shinjuku-ku	Tokyo
Japan	Tomonaga Clinic	Shinjuku-ku	Tokyo
Japan	Suruga Clinic	Shizuoka
Japan	Shinei Clinic	Suginami	Tokyo
Japan	Medical Corporation Heishinkai OCROM Clinic	Suita-shi	Osaka
Japan	Takatsuki Red Cross Hospital	Takatsuki	Osaka
Japan	Ikebukuro Metropolitan Clinic	Toshima-ku	Tokyo
Japan	Senrichuo Ekimae Clinic	Toyonaka	Osaka
Japan	H.E.C. Science Clinic	Yokohama	Kanagawa
Japan	Yokohama Minoru Clinic	Yokohama

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c)	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 + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Percentage of Participants With HbA1c of <7.0%	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 52
Secondary	Change From Baseline in Fasting Serum Glucose	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 + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Change From Baseline in Average 7-Point Self-Monitored Blood Glucose (SMBG) Values	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 with Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment (Type III sum of squares) as variables.	Baseline, Week 52
Secondary	Change From Baseline in Body Weight	Change from baseline in body weight. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Percentage of Participants Who Achieve Weight Loss =5% From Baseline	Percentage of participants who achieve weight loss =5% from baseline.	Week 52
Secondary	Change From Baseline in Fasting Insulin	Fasting Insulin is a test used to measure the amount of insulin in the body. LS mean was determined by MMRM model for post-baseline measures with log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 52
Secondary	Change From Baseline in Fasting C-Peptide	Fasting C-peptide is a test used to measure the amount of C-peptide in the body. A high level of C-peptide can mean that body is making too much insulin. LS mean was determined by MMRM model for post-baseline measures: log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Change From Baseline in Homeostasis Model Assessment B (HOMA-2B, Insulin)	HOMA-2B is an estimated steady state beta cell function based on updated HOMA2 model. The HOMA2 model estimates steady state pancreatic beta cell function (%B) as a percentage of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Change From Baseline in HOMA-2S (Insluin)	HOMA2-S is an estimated insulin sensitivity based on updated HOMA2 model. The HOMA2 model is a computer model that estimates insulin sensitivity (%S) as percentages of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Rate of Hypoglycemia With Glucose < 54 mg/dL or Severe Hypoglycemia	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 for post-baseline comparisons between treatment and control group: number of episodes = baseline hypoglycemia incidence + baseline BMI Group (<25 or >=25 kg/m^2) + washout of antidiabetic medication + baseline hemoglobin A1C (%) + treatment, with log (exposure in days/365.25) as an offset variable.	Baseline through Week 52
Secondary	Number of Participants With Anti-Tirzepatide Antibodies	Number of participants with anti-tirzepatide antibodies. A participant is treatment emergent (TE) anti-drug antibody (ADA) evaluable if there is at least one non-missing test result for tirzepatide ADA for each of the baseline period and the postbaseline period. All percentages are relative to the total number of TE ADA evaluable participants in each treatment group. A TE ADA evaluable participant is considered to be TE ADA+ if the participant has at least one postbaseline titer that is a 4-fold or greater increase in titer from baseline measurement.	Baseline through Week 52