Clinical trial NCT03861039: A Long-term Safety Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-03-04
Enrollment: 443
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline through Week 52
Secondary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c)
timeFrame: Baseline, Week 52
measure: Percentage of Participants Who Achieve HbA1c <7%
timeFrame: Week 52
measure: Change From Baseline in Fasting Serum Glucose
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
timeFrame: Baseline, Week 52
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Week 52
measure: Percentage of Participants Who Achieve Weight Loss of ≥5% From Baseline
timeFrame: Week 52
measure: Change From Baseline in Fasting Insulin
timeFrame: Baseline, Week 52
measure: Change From Baseline in Fasting C-Peptide
timeFrame: Baseline, Week 52
measure: Change From Baseline in Homeostasis Model Assessment B (HOMA-2B) (Insulin)
timeFrame: Baseline, Week 52
measure: Change From Baseline in HOMA-2S (Insulin)
timeFrame: Baseline, Week 52
measure: 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
timeFrame: Baseline through Week 56
measure: Number of Participants With Anti-Tirzepatide Antibodies
timeFrame: Baseline through Week 52
Other outcomes:
Locations:
city: Chiba-shi
country: Japan
facility: Akaicho Clinic
state: Chiba
city: Kashiwa
country: Japan
facility: Kashiwa hospital
state: Chiba
city: Sapporo
country: Japan
facility: Yuri Ono Clinic
state: Hokkaido
city: Sapporo
country: Japan
facility: Manda Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Miyanomori Hospital
state: Hokkaido
city: Amagasaki
country: Japan
facility: Ikeda Hospital
state: Hyogo
city: Mito
country: Japan
facility: Nakamoto Naika Clinic
state: Ibaraki
city: Naka
country: Japan
facility: Naka Memorial Clinic
state: Ibaraki
city: Tsuchiura
country: Japan
facility: Ohishi Naika Clinic
state: Ibaraki
city: Kamakura
country: Japan
facility: Takai Naika Clinic
state: Kanagawa
city: Yamato
country: Japan
facility: Tsuruma Kaneshiro Diabetes Clinic
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama Minoru Clinic
state: Kanagawa
city: Yokohama
country: Japan
facility: H.E.C. Science Clinic
state: Kanagawa
city: Takatsuki
country: Japan
facility: Takatsuki Red Cross Hospital
state: Osaka
city: Otsu
country: Japan
facility: Otsu City Hospital
state: Shiga
city: Shimotsuke
country: Japan
facility: Wakakusa Clinic
state: Tochigi
city: Adachi-ku
country: Japan
facility: Seiwa Clinic
state: Tokyo
city: Chiyoda
country: Japan
facility: HDC Atlas Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Asahi Life Foundation Adult Disease Research Center
state: Tokyo
city: Chuo-ku
country: Japan
facility: Nihonbashi Sakura Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Tokyo-Eki Center-building Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Tokyo Center Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Tokyo Clinical Trial Centre Fukuwa Clinic
state: Tokyo
city: Mitaka
country: Japan
facility: Kanno Naika
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Shinjuku Research Park Clinic
state: Tokyo
city: Fukuoka
country: Japan
facility: Futata Tetsuhiro Clinic
city: Kumamoto
country: Japan
facility: Morinaga Ueno Clinic
city: Kumamoto
country: Japan
facility: Jinnouchi Hospital
city: Oita
country: Japan
facility: Abe Diabetes Clinic
city: Osaka
country: Japan
facility: Saiseikai Noe Hospital
city: Osaka
country: Japan
facility: Kitada Clinic
city: Osaka
country: Japan
facility: Kansai Denryoku Hospital
city: Shizuoka
country: Japan
facility: Shizuoka City Shizuoka Hospital
city: Shizuoka
country: Japan
facility: Suruga Clinic
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Kadowaki T, Chin R, Ozeki A, Imaoka T, Ogawa Y. Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2022 Sep;10(9):634-644. doi: 10.1016/S2213-8587(22)00187-5. Epub 2022 Jul 30.