Clinical trial NCT02759107: A Study of Tirzepatide (LY3298176) in Healthy Participants and Participants With Type 2 Diabetes (T2DM)
Official title: A Single- and Multiple-Ascending Dose Study in Healthy Subjects to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3298176 and Multiple Doses in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Type 2 Diabetes Mellitus (T2DM)
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-05-03
Enrollment: 142
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The main purposes of this study are to determine:

* The safety of tirzepatide and any side effects that might be associated with it.
* How much tirzepatide gets into the bloodstream and how long it takes the body to get rid of it.
* How tirzepatide affects the levels of blood sugar.

This study includes 3 parts (A, B and C). Part A involves a single dose of tirzepatide taken as a subcutaneous (SC) injection just under the skin and will be approximately 10 weeks in duration, including screening. Parts B and C involve 4 doses of tirzepatide taken once weekly (over 4 weeks) as a SC injection just under the skin and is approximately 12-14 weeks in duration, including screening. Each participant will enroll in only one part.

This study is for research purposes only, and is not intended to treat any medical condition.


Eligibility criteria: Inclusion Criteria:

* Healthy participants (Parts A and B) and participants with T2DM diagnosed at least 1 year before enrollment (Part C)
* Have a screening body mass index (BMI) of greater than 18.5 and less than or equal to 40.0 kilograms per meter squared (kg/m²), inclusive
* Participants with T2DM (Part C only): have T2DM controlled with diet and exercise alone or are stable on a single oral antidiabetic medication (metformin for at least 30 days or sulfonylureas). Participants receiving sulfonylureas may participate only if this treatment is stopped for at least 6 weeks before dosing with study drug

Exclusion Criteria:

* Have known allergies to tirzepatide, glucagon-like peptide (GLP)-1 analogs, or related compounds
* Have an abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator, increases the risks associated with participating in the study
* Have a history or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis), elevation in serum amylase or lipase (greater than 2-fold the upper limit of normal \[ULN\]) or gastrointestinal (GI) disorder (for example, relevant esophageal reflux or gall bladder disease) or any GI disease which impacts gastric emptying (for example, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by glucagon-like peptide-1 (GLP-1) analogs or dipeptidyl peptidase (DPP)-IV inhibitors

Participants with T2DM (Part C only)

* Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before entry into the study or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms

All Study Participants (Parts B and C only)

* have known allergies to tirzepatide, GLP-1 analogs, or related compounds, or acetaminophen

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Event(s) (SAEs)
timeFrame: Baseline through Day 43 (Part A) and Day 57 (Part B and C)
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part A.
timeFrame: Predose, 8hours(h), 24h,48h,72h,96h,120h,168h,336h postdose, day 29, day 43
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part B
timeFrame: Predose, 8hours(h), 24h,48h,72h,168h postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part C
timeFrame: Predose, 8hours(h), 24h,48h,72h,168h postdose
measure: Pharmacodynamics (PD): Ratio of AUC of Glucose on Day 2 to Baseline (Part C)
timeFrame: Pre-glucose dose, 0.5, 1, 1.5, 2 hours post-glucose dose on Day -1 and Day 2
measure: Pharmacodynamics (PD): Ratio of AUC of Glucose on Day 23 to Baseline (Part C)
timeFrame: Pre-glucose dose, 0.5, 1, 1.5, 2 hours post-glucose dose on Day -1 and Day 23
Other outcomes:
Locations:
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Singapore
country: Singapore
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
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: Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3.