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

Type 2 Diabetes Mellitus Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03861039
• Other study ID #: 17078
• Secondary ID: I8F-JE-GPGP
• Status: Completed
• Phase: Phase 3
• Start date: March 30, 2019
• Est. completion date: February 16, 2021

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 443
• Est. completion date: February 16, 2021
• Est. primary completion date: January 26, 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 =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.

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Japan	Seiwa Clinic	Adachi-ku	Tokyo
Japan	Ikeda Hospital	Amagasaki	Hyogo
Japan	Akaicho Clinic	Chiba-shi	Chiba
Japan	HDC Atlas Clinic	Chiyoda	Tokyo
Japan	Asahi Life Foundation Adult Disease Research Center	Chuo-ku	Tokyo
Japan	Nihonbashi Sakura Clinic	Chuo-ku	Tokyo
Japan	Tokyo Center Clinic	Chuo-ku	Tokyo
Japan	Tokyo Clinical Trial Centre Fukuwa Clinic	Chuo-ku	Tokyo
Japan	Tokyo-Eki Center-building Clinic	Chuo-ku	Tokyo
Japan	Futata Tetsuhiro Clinic	Fukuoka
Japan	Takai Naika Clinic	Kamakura	Kanagawa
Japan	Kashiwa hospital	Kashiwa	Chiba
Japan	Jinnouchi Hospital	Kumamoto
Japan	Morinaga Ueno Clinic	Kumamoto
Japan	Kanno Naika	Mitaka	Tokyo
Japan	Nakamoto Naika Clinic	Mito	Ibaraki
Japan	Naka Memorial Clinic	Naka	Ibaraki
Japan	Abe Diabetes Clinic	Oita
Japan	Kansai Denryoku Hospital	Osaka
Japan	Kitada Clinic	Osaka
Japan	Saiseikai Noe Hospital	Osaka
Japan	Otsu City Hospital	Otsu	Shiga
Japan	Manda Hospital	Sapporo	Hokkaido
Japan	Miyanomori Hospital	Sapporo	Hokkaido
Japan	Yuri Ono Clinic	Sapporo	Hokkaido
Japan	Wakakusa Clinic	Shimotsuke	Tochigi
Japan	Shinjuku Research Park Clinic	Shinjuku-Ku	Tokyo
Japan	Shizuoka City Shizuoka Hospital	Shizuoka
Japan	Suruga Clinic	Shizuoka
Japan	Takatsuki Red Cross Hospital	Takatsuki	Osaka
Japan	Ohishi Naika Clinic	Tsuchiura	Ibaraki
Japan	Tsuruma Kaneshiro Diabetes Clinic	Yamato	Kanagawa
Japan	H.E.C. Science Clinic	Yokohama	Kanagawa
Japan	Yokohama Minoru Clinic	Yokohama	Kanagawa

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	Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	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.	Baseline through Week 52
Secondary	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 + oral antihyperglycemic medication (OAM) Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Percentage of Participants Who Achieve HbA1c <7%	Hemoglobin A1c (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 + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Mean Change From Baseline in Daily 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 endpoint measures: Variable = Baseline + OAM Group 1 + Treatment (Type III sum of squares).	Baseline, Week 52
Secondary	Change From Baseline in Body Weight	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).	Baseline, Week 52
Secondary	Percentage of Participants Who Achieve Weight Loss of =5% From Baseline	Percentage of Participants who Achieve Weight Loss of =5% from Baseline	Week 52
Secondary	Change From Baseline in Fasting Insulin	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).	Baseline, Week 52
Secondary	Change From Baseline in Fasting C-Peptide	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).	Baseline, Week 52
Secondary	Change From Baseline in Homeostasis Model Assessment B (HOMA-2B) (Insulin)	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).	Baseline, Week 52
Secondary	Change From Baseline in HOMA-2S (Insulin)	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).	Baseline, Week 52
Secondary	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	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.	Baseline through Week 56
Secondary	Number of Participants With Anti-Tirzepatide Antibodies	Number of Participants with Anti-Tirzepatide Antibodies	Baseline through Week 52

External Links

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