Clinical trial NCT04039503: A Study of Tirzepatide (LY3298176) Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: glucose-dependent insulinotropic polypeptide (GIP)
glucagon-like peptide-1 (GLP-1)
GIP/GLP-1 dual receptor agonist
T2DM
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-07-31
Enrollment: 475
Sex: ALL
Minimum age (years): 18
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
timeFrame: Baseline, Week 40
Secondary outcomes:
measure: Change From Baseline in HbA1c (5 mg)
timeFrame: Baseline, Week 40
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Week 40
measure: Percentage of Participants Achieving an HbA1c Target Value of <7%
timeFrame: Week 40
measure: Change From Baseline in Fasting Serum Glucose
timeFrame: Baseline, Week 40
measure: Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
timeFrame: Baseline, Week 40
measure: Percentage of Participants Who Achieved Weight Loss ≥5%
timeFrame: Week 40
measure: Percentage Change From Baseline in Daily Mean Insulin Glargine Dose
timeFrame: Baseline, Week 40
measure: Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia
timeFrame: Baseline through Safety Follow-Up (Up to Week 44)
measure: Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide
timeFrame: Week 7, 15, 23 and 39 post dose
measure: Percentage of Participants Achieving an HbA1c Target Value of <5.7%
timeFrame: Week 40
Other outcomes:
Locations:
city: Fresno
country: United States
facility: Valley Endocrine, Fresno
state: California
city: New Port Richey
country: United States
facility: Sun Coast Clinical Research, Inc
state: Florida
city: Nashua
country: United States
facility: Southern New Hampshire Diabetes and Endocrinology
state: New Hampshire
city: New York
country: United States
facility: Manhattan Medical Research
state: New York
city: Norman
country: United States
facility: Intend Research
state: Oklahoma
city: Pribram
country: Czechia
facility: Milan Kvapil s.r.o.
state: Středočeský Kraj
city: Brandys Nad Labem-Stara Bolesl
country: Czechia
facility: Diacentrum Brandys n.L. s.r.o.
city: Krnov
country: Czechia
facility: Diabetologicka ordinace pro dospele
city: Pardubice
country: Czechia
facility: Diahelp s.r.o., Interni a diabetologicka ambulance
city: Praha 1
country: Czechia
facility: Lekarna Dr. Max
city: Praha 4
country: Czechia
facility: Milan Kvapil s.r.o.
city: Praha 8
country: Czechia
facility: RESTRIAL s.r.o.
city: Falkensee
country: Germany
facility: Praxis Dr. Jörg Lüdemann
state: Brandenburg
city: Pohlheim
country: Germany
facility: Arztpraxis Dr. Cornelia Marck
state: Hessen
city: Essen
country: Germany
facility: InnoDiab Forschung GmbH
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Institut für Diabetesforschung Münster GmbH
state: Nordrhein-Westfalen
city: Ludwigshafen am Rhein
country: Germany
facility: Praxis Dr. Kempe - Dr. Stemler
state: Rheinland-Pfalz
city: Saint Ingbert-Oberwürzbach
country: Germany
facility: Schwerpunktpraxis Diabetes
state: Saarland
city: Magdeburg
country: Germany
facility: SMO.MD GmbH
state: Sachsen-Anhalt
city: Oldenburg in Holstein
country: Germany
facility: RED-Institut GmbH
state: Schleswig Holstein
city: Hamburg
country: Germany
facility: Diabetologische Schwerpunktpraxis B. Scholz/Dr. B. Paschen
city: Hamburg
country: Germany
facility: Gemeinschaftspraxis für innere Medizin und Diabetologie
city: Kashiwa
country: Japan
facility: Kashiwa hospital
state: Chiba
city: Sapporo
country: Japan
facility: Manda Hospital
state: Hokkaido
city: Kamakura
country: Japan
facility: Takai Naika Clinic
state: Kanagawa
city: Takatsuki
country: Japan
facility: Takatsuki Red Cross Hospital
state: Osaka
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: Chuou-ku
country: Japan
facility: The Institute for Adult Diseases, Asahi Life Foundation
state: Tokyo
city: Ota-ku
country: Japan
facility: Sato Naika Clinic
state: Tokyo
city: Kumamoto
country: Japan
facility: Jinnouchi Hospital
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED
state: Mazowieckie
city: Bialystok
country: Poland
facility: NZOZ ZDROWIE Osteo-Medic
state: Podlaskie
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych, PI House
state: Pomorskie
city: Lublin
country: Poland
facility: NZOZ Przychodnia Specjalistyczna MEDICA
city: Caguas
country: Puerto Rico
facility: Centro de Endocrinologia y Nutricion del Turabo
city: Manati
country: Puerto Rico
facility: Manati Center for Clinical Research Inc
city: Hnusta
country: Slovakia
facility: Ambulancia vnútorného lekárstva Hnúša (Diabetes care)
city: Malacky
country: Slovakia
facility: Sin Azucar
city: Prievidza
country: Slovakia
facility: Dia-Clarus.s.r.o.
city: Trnava
country: Slovakia
facility: JAL
city: Zilina
country: Slovakia
facility: Medivasa, s.r.o.
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
state: Andalucia
city: Alcira
country: Spain
facility: Hospital de la Ribera
state: Valencia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa
city: València
country: Spain
facility: Hospital Universitari i Politecnic La Fe-ENDO
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: Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, Zoungas S. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022 Mar;28(3):591-598. doi: 10.1038/s41591-022-01707-4. Epub 2022 Feb 24.
citation: Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, Rodriguez A. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022 Feb 8;327(6):534-545. doi: 10.1001/jama.2022.0078.