A Study of Tirzepatide (LY3298176) Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin

Type 2 Diabetes Clinical Trial

— SURPASS-5  

Official title:

Randomized, Phase 3, Double-blind Trial Comparing the Effect of the Addition of Tirzepatide Versus Placebo in Patients With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04039503
• Other study ID #: 16998
• Secondary ID: I8F-MC-GPGI2019-
• Status: Completed
• Phase: Phase 3
• Start date: August 30, 2019
• Est. completion date: January 13, 2021

Study information

• Verified date: December 1, 2021
• 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 compare the safety and efficacy of the study drug tirzepatide to placebo in participants with type 2 diabetes that are already on insulin glargine, with or without metformin. Participants will administer tirzepatide or placebo along with their previous glucose lowering medications. The study will last approximately 47 weeks and may include about 23 visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 475
• Est. completion date: January 13, 2021
• Est. primary completion date: December 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have been diagnosed with type 2 diabetes mellitus (T2DM) and have been treated with insulin glargine (U100), once daily with or without metformin =3 months prior to screening visit.

• Have HbA1c between =7.0% and =10.5%.

• Have a stable weight (± 5%) for at least 3 months before screening.

• Have a body mass index (BMI) =23 kilograms per meter squared (kg/m²) at screening.

Exclusion Criteria:

• 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 acute treatment.

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

• Have an estimated glomerular filtration rate <30 mL/minute/1.73 m² [for participants on metformin, estimated glomerular filtration rate <45 mL/min/1.73 m2 (or lower than the country-specific threshold for using the protocol-required dose of metformin per local label)]

• 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 as add-on to the pre-trial background medication.
• Placebo
Administered SC as add-on to the pre-trial background medication.

Locations

Country	Name	City	State
Czechia	Diacentrum Brandys n.L. s.r.o.	Brandys Nad Labem-Stara Bolesl
Czechia	Diabetologicka ordinace pro dospele	Krnov
Czechia	Diahelp s.r.o., Interni a diabetologicka ambulance	Pardubice
Czechia	Lekarna Dr. Max	Praha 1
Czechia	Milan Kvapil s.r.o.	Praha 4
Czechia	RESTRIAL s.r.o.	Praha 8
Czechia	Milan Kvapil s.r.o.	Pribram	Stredoceský Kraj
Germany	InnoDiab Forschung GmbH	Essen	Nordrhein-Westfalen
Germany	Praxis Dr. Jörg Lüdemann	Falkensee	Brandenburg
Germany	Diabetologische Schwerpunktpraxis B. Scholz/Dr. B. Paschen	Hamburg
Germany	Gemeinschaftspraxis für innere Medizin und Diabetologie	Hamburg
Germany	Praxis Dr. Kempe - Dr. Stemler	Ludwigshafen am Rhein	Rheinland-Pfalz
Germany	SMO.MD GmbH	Magdeburg	Sachsen-Anhalt
Germany	Institut für Diabetesforschung Münster GmbH	Münster	Nordrhein-Westfalen
Germany	RED-Institut GmbH	Oldenburg in Holstein	Schleswig Holstein
Germany	Arztpraxis Dr. Cornelia Marck	Pohlheim	Hessen
Germany	Schwerpunktpraxis Diabetes	Saint Ingbert-Oberwürzbach	Saarland
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	The Institute for Adult Diseases, Asahi Life Foundation	Chuou-ku	Tokyo
Japan	Takai Naika Clinic	Kamakura	Kanagawa
Japan	Kashiwa hospital	Kashiwa	Chiba
Japan	Jinnouchi Hospital	Kumamoto
Japan	Sato Naika Clinic	Ota-ku	Tokyo
Japan	Manda Hospital	Sapporo	Hokkaido
Japan	Takatsuki Red Cross Hospital	Takatsuki	Osaka
Poland	NZOZ ZDROWIE Osteo-Medic	Bialystok	Podlaskie
Poland	Centrum Badan Klinicznych, PI House	Gdansk	Pomorskie
Poland	NZOZ Przychodnia Specjalistyczna MEDICA	Lublin
Poland	Centrum Medyczne AMED	Warszawa	Mazowieckie
Puerto Rico	Centro de Endocrinologia y Nutricion del Turabo	Caguas
Puerto Rico	Manati Center for Clinical Research Inc	Manati
Slovakia	Ambulancia vnútorného lekárstva Hnúša (Diabetes care)	Hnusta
Slovakia	Sin Azucar	Malacky
Slovakia	Dia-Clarus.s.r.o.	Prievidza
Slovakia	JAL	Trnava
Slovakia	Medivasa, s.r.o.	Zilina
Spain	Hospital de la Ribera	Alcira	Valencia
Spain	Hospital Clinico Universitario Virgen de la Victoria	Malaga	Andalucia
Spain	Hospital Infanta Luisa	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitari i Politecnic La Fe-ENDO	València
United States	Valley Endocrine, Fresno	Fresno	California
United States	Southern New Hampshire Diabetes and Endocrinology	Nashua	New Hampshire
United States	Sun Coast Clinical Research, Inc	New Port Richey	Florida
United States	Manhattan Medical Research	New York	New York
United States	Intend Research	Norman	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Japan,  Poland,  Puerto Rico,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
Secondary	Change From Baseline in HbA1c (5 mg)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
Secondary	Change From Baseline in Body Weight	Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (<= 8.0%, >8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
Secondary	Percentage of Participants Achieving an HbA1c Target Value of <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 40
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 with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 40
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. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (<= 8.0%, >8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment (Type III sum of squares).	Baseline, Week 40
Secondary	Percentage of Participants Who Achieved Weight Loss =5%	Percentage of Participants who Achieved Weight Loss =5%.	Week 40
Secondary	Percentage Change From Baseline in Daily Mean Insulin Glargine Dose	LS mean was calculated using MMRM model with log (Baseline) + Baseline Metformin Use (Yes, No) + Pooled Country + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 40
Secondary	Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] 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: number of episodes = Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment, with log (exposure in days/365.25) as an offset variable.	Baseline through Safety Follow-Up (Up to Week 44)
Secondary	Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide	AUC is a combined measure obtained from Week 7, 15, 23 and 39 and a single averaged measure of AUC was reported.	Week 7, 15, 23 and 39 post dose
Secondary	Percentage of Participants Achieving an HbA1c Target Value of <5.7%	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 40

External Links

•   A Study of Tirzepatide (LY3298176) Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin