CClinicalTrials.gg
Sign In
CompletedNCT03322631Updated Mar 23, 2023Results posted

A Study of Tirzepatide (LY3298176) in Japanese Participants With Type 2 Diabetes

A Phase 1 interventional study of Tirzepatide and Placebo in Type 2 Diabetes Mellitus, sponsored by Eli Lilly and Company. Completed at 2 sites in Japan. Open to participants aged 20 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-03-23.

Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
48
Allocation
Randomized
Ages
20 Years to 70 Years
Sex
All
01

Study summary

The 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 remove it.
  • How tirzepatide affects the levels of blood sugar.

This study includes eight weekly doses of tirzepatide or placebo given as subcutaneous (SC) injections just under the skin. The study will last about 16 weeks (total), including screening and follow-up. This study is for research purposes only and is not intended to treat any medical conditions.

02

Conditions studied

  • Type 2 Diabetes Mellitus
03

Who can participate

Ages eligible
20 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Have T2DM controlled with diet and exercise alone or are stable on a single oral antidiabetic medication (metformin or dipeptidyl peptidase [DPP]-IV inhibitors)
  • Have a body mass index of 20.0 to 35.0 kilograms per square meter, inclusive

Exclusion criteria

Exclusion Criteria:

  • Have known allergies to tirzepatide, glucagon-like peptide (GLP)-1 analogs, or related compounds
  • 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
  • Have an abnormality in the 12-lead electrocardiogram 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 or gastrointestinal (GI) disorder or any GI disease which impacts gastric emptying or could be aggravated by GLP-1 analogs or DPP-IV inhibitors
04

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
48 participants (actual)

Study arms

  • Experimental
    Tirzepatide

    Participants received escalating doses of 2.5 milligrams (mg), 5 mg, 10 mg and 15 mg of tirzepatide administered into the subcutaneous (SC) tissue of the abdominal wall.

    Drug: Tirzepatide

  • Placebo comparator
    Placebo

    Participants received placebo administered into the SC tissue of the abdominal wall.

    Drug: Placebo

Interventions

  • DrugTirzepatide

    Administered SC.

    Also known as: LY3298176

  • DrugPlacebo

    Administered SC.

05

What researchers measure

Primary outcomes

  1. Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

    Safety was assessed from time of consent through end of study (up to 85 days). Data presented are the number of participants who experienced 1 or more SAEs considered by the investigator to be related to study drug. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record.

    Time frame: Baseline through Day 85

Secondary outcomes

  1. Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide

    Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of Tirzepatide in plasma.

    Time frame: Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration

  2. PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide

    Area under the concentration versus time curve from time zero to tau (τ) of Tirzepatide (AUC\[0- τ\]), where tau is dosing interval of (0-168 hours).

    Time frame: Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration

  3. Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose

    Change from baseline to 8 weeks in Fasting Plasma Glucose was measured to investigate the PD effect of Tirzepatide after multiple SC doses administered to Japanese patients with T2DM

    Time frame: Baseline, Week 8

06

Results

Posted Mar 23, 2023

Participant flow

Participant flow — Overall Study
MilestonePlacebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)
Started9121611
Received at least 1 dose of study drug9121611
Completed9111511
Not completed0110
Withdrew: Withdrawal by subject0100
Withdrew: Adverse event0010

Outcome measures

PrimaryNumber of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

Safety was assessed from time of consent through end of study (up to 85 days). Data presented are the number of participants who experienced 1 or more SAEs considered by the investigator to be related to study drug. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record.

Time frame:
Baseline through Day 85
Reported as:
Count of participants · Participants
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
ParticipantsPlacebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration0000
SecondaryPharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide

Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of Tirzepatide in plasma.

Time frame:
Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration
Reported as:
Geometric mean · nanograms per milliliter (ng/mL)
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide
nanograms per milliliter (ng/mL)2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)
Day 1215 ± 18442 ± 23364 ± 20
Day 501520 ± 152270 ± 17838 ± 22
SecondaryPK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide

Area under the concentration versus time curve from time zero to tau (τ) of Tirzepatide (AUC\[0- τ\]), where tau is dosing interval of (0-168 hours).

Time frame:
Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration
Reported as:
Geometric mean · nanograms * hours per mL (ng*hr/mL)
PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide
nanograms * hours per mL (ng*hr/mL)2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)
Day 126100 ± 2754400 ± 1648800 ± 16
Day 50192000 ± 16285000 ± 15104000 ± 19
SecondaryPharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose

Change from baseline to 8 weeks in Fasting Plasma Glucose was measured to investigate the PD effect of Tirzepatide after multiple SC doses administered to Japanese patients with T2DM

Time frame:
Baseline, Week 8
Reported as:
Mean · milligram per deciliter (mg/dL)
Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose
milligram per deciliter (mg/dL)Placebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)
Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose-4.0 ± 23.7-77.5 ± 24.2-72.6 ± 30.9-51.7 ± 28.9

Adverse events

Collected over Up To 85 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/9 (0%)0/9 (0%)4/9 (44.4%)
2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)0/12 (0%)0/12 (0%)11/12 (91.7%)
5 mg/10 mg/15 mg Tirzepatide (Cohort 2)0/16 (0%)0/16 (0%)15/16 (93.8%)
5 mg Tirzepatide (Cohort 3)0/11 (0%)0/11 (0%)6/11 (54.5%)
Most frequent other events
Showing 10 of 22
Most frequent other events
EventPlacebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)
ConstipationGastrointestinal disorders1/98/128/160/11
Decreased appetiteMetabolism and nutrition disorders0/96/1210/165/11
DiarrhoeaGastrointestinal disorders0/93/125/160/11
Abdominal distensionGastrointestinal disorders1/91/120/163/11
Abdominal discomfortGastrointestinal disorders0/92/124/160/11
DyspepsiaGastrointestinal disorders0/93/120/160/11
HeadacheNervous system disorders0/93/121/160/11
Blood triglycerides increasedInvestigations2/90/121/160/11
NauseaGastrointestinal disorders0/90/122/161/11
VomitingGastrointestinal disorders0/91/122/161/11

Baseline characteristics

All randomized participants who received at least one dose of study drug.

Age, Continuous
Age, Continuous(Years)Placebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)Total
Mean57.4 ± 11.656.9 ± 9.557.7 ± 8.057.5 ± 7.957.4 ± 8.8
Sex: Female, Male
Sex: Female, Male(Participants)Placebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)Total
Female00101
Male912151147
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Placebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)Total
Hispanic or Latino00000
Not Hispanic or Latino912161148
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)Total
American Indian or Alaska Native00000
Asian912161148
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White00000
More than one race00000
Unknown or Not Reported00000
Region of Enrollment
Region of Enrollment(Participants)Placebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)Total
Japan912161148
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m²)Placebo2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1)5 mg/10 mg/15 mg Tirzepatide (Cohort 2)5 mg Tirzepatide (Cohort 3)Total
Mean22.58 ± 2.0925.49 ± 2.7526.10 ± 3.1126.68 ± 3.2925.42 ± 3.16
07

Study locations

2 sites
  • 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.
    Hachioji, Tokyo 192-0071, Japan
  • 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.
    Shinjuku-Ku, Tokyo 169-0073, Japan
08

References and documents

Study documents

  • Study protocol · Oct 15, 2018
  • Statistical analysis plan · Nov 22, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03322631
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Oct 26, 2017
Start date
Nov 15, 2017
Primary completion
May 29, 2018
Completion
Nov 28, 2018
Results posted
Mar 23, 2023
Last update
Mar 23, 2023

Study contacts

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)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Diabetes Mellitus→

Other studies from this sponsor

Eli Lilly and Company

Start the discussion