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Efficacy and Safety of Once Weekly Tirzepatide in Participants with Obesity Disease: A Randomized, Double Blind, Placebo Controlled Trial (SURMOUNT-J) (I8F-JE-GPHZ)

A Study of Tirzepatide (LY3298176) in Participants With Obesity Disease (SURMOUNT-J) (I8F-JE-GPHZ)

267

This study included 267 total participants, but 42 did not meet certain criteria to have their results analyzed [because the results were obtained at a Japanese site where good clinical practice (GCP) compliance issues were identified]. So, this summary includes results from 225 Japanese participants with obesity disease. This was 133 males and 92 females. These participants were 22 to 80 years old in Japan. In this summary, along with the results by excluding participants from the site with GCP issues, the results of the entire participants (group before the exclusion) are also shown as reference. The main data of baseline characteristics were; Age: Mean (Standard Deviation), Unit of measure: years - 10 mg Tirzepatide (73 participants): 49.00 (10.87) [group before the exclusion (88 participants): 48.9 (10.8)] - 15 mg Tirzepatide (77 participants): 51.10 (10.30) [group before the exclusion (90 participants): 51.4 (9.8)] - Placebo (75 participants): 52.30 (10.93) [group before the exclusion (89 participants): 52.2 (10.6)] Sex: Female, Male, Unit of measure: Participants - 10 mg Tirzepatide (73 participants): Female 30, Male 43[group before the exclusion (88 participants): Female 37, Male 51] - 15 mg Tirzepatide (77 participants): Female 32, Male 45[group before the exclusion (90 participants): Female 39, Male 51] - Placebo (75 participants): Female 30, Male 45 [group before the exclusion (89 participants): Female 38, Male 51]

The participants in this study received tirzepatide or a placebo. A placebo looks like a drug but does not have any drug in it. Researchers use a placebo to help make sure the effects they see in the participants who receive the drug are actually caused by the drug. This was a 'double-blind' study. This means none of the participants, doctors, or other study staff knew what treatment each participant received. Some studies are done this way because knowing what treatment the participants are receiving can affect the results of the study. When the study ended, Lilly was provided information about which treatment participants received so they could create a report of the study results. The researchers used a computer program to randomly choose the treatment each participant received. Researchers do this so that comparing the results of each treatment is as accurate as possible. The treatment plan for the participants is shown below. The doses of tirzepatide were measured in milligrams (mg). Group 1 - 73 participants (group before the exclusion: 88 participants) - 10 mg of tirzepatide Group 2 - 77 participants (group before the exclusion: 90 participants) - 15 mg of tirzepatide Group 3 - 75 participants (group before the exclusion: 89 participants) - Placebo Through an injection under the skin Once a week for 72 weeks The participants who were assigned to receive tirzepatide started out receiving a low dose of 2.5 mg of tirzepatide. For up to the first 20 weeks of treatment, their dose increased every 4 weeks until they were receiving the full dose of tirzepatide assigned to their group (10 mg or 15 mg). Then, the participants received either 10 mg or 15 mg doses of tirzepatide for the rest of the study. The patient flow was; - 10 mg Tirzepatide: Started 88, Received At Least 1 Dose of Study Drug (Excluding the GCP Compliance Investigative Site) 73, Completed 60 (group before the exclusion: Started 88, Received At Least 1 Dose of Study Drug 88, Completed 75) - 15 mg Tirzepatide: Started 90, Received At Least 1 Dose of Study Drug (Excluding the GCP Compliance Investigative Site) 77, Completed 65 (group before the exclusion: Started 90, Received At Least 1 Dose of Study Drug 90, Completed 76) - Placebo: Started 89, Received At Least 1 Dose of Study Drug (Excluding the GCP Compliance Investigative Site) 75, Completed 67 (group before the exclusion: Started 89, Received At Least 1 Dose of Study Drug 89, Completed 81)

Any medical problems that happen during a study are called 'adverse events'. This section is a summary of the adverse events the doctors reported as possibly related to the study treatment. An adverse event is considered 'serious' when it requires hospital care, is life-threatening, or causes lasting problems. One study is not enough evidence to determine if an adverse event is caused by the study treatment. A lot of research is needed to know whether a treatment causes a possibly related adverse event. In this study, the doctors did not know what the participants were receiving when the medical problems happened. So, the doctors may have reported some adverse events in participants who received the placebo, even though the placebo does not directly cause medical problems. How many participants had adverse events that were possibly related to the study treatment? - How many participants had serious adverse events that were possibly related to the study treatment?: 10 mg of tirzepatide 0% (0 out of 73 participants), 15 mg of tirzepatide 0% (0 out of 77 participants), Placebo 0% (0 out of 75 participants) [group before the exclusion: 10 mg of tirzepatide 0% (0 out of 88 participants), 15 mg of tirzepatide 0% (0 out of 90 participants), Placebo 0% (0 out of 89 participants)] - How many participants had adverse events that were possibly related to the study treatment?: 10 mg of tirzepatide 56.2% (41 out of 73 participants), 15 mg of tirzepatide 63.6% (49 out of 77 participants), Placebo 10.7% (8 out of 75 participants) [group before the exclusion: 10 mg of tirzepatide 53.4% (47 out of 88 participants), 15 mg of tirzepatide 61.1% (55 out of 90 participants), Placebo 10.1% (9 out of 89 participants)] - How many participants stopped receiving treatment due to adverse events that were possibly related to the study treatment?: 10 mg of tirzepatide 6.8% (5 out of 73 participants), 15 mg of tirzepatide 7.8% (6 out of 77 participants), Placebo 0% (0 out of 75 participants) [group before the exclusion: 10 mg of tirzepatide 5.7% (5 out of 88 participants), 15 mg of tirzepatide 8.9% (8 out of 90 participants), Placebo 0% (0 out of 89 participants)] What were the adverse events that were possibly related to the study treatment? The most common adverse event that was possibly related to the study treatment was constipation. The adverse events that were possibly related to the study treatment that were reported in 5.0% or more of participants in any of the groups are shown below. There were other possibly related adverse events, but they were reported in fewer participants. - Constipation: 10 mg of tirzepatide 13.7% (10 out of 73 participants), 15 mg of tirzepatide 23.4% (18 out of 77 participants), Placebo 2.7% (2 out of 75 participants) [group before the exclusion: 10 mg of tirzepatide 13.6% (12 out of 88 participants), 15 mg of tirzepatide 24.4% (22 out of 90 participants), Placebo 2.2% (2 out of 89 participants)] - Nausea: 10 mg of tirzepatide 13.7% (10 out of 73 participants), 15 mg of tirzepatide 22.1% (17 out of 77 participants), Placebo 0% (0 out of 75 participants) [group before the exclusion: 10 mg of tirzepatide 14.8% (13 out of 88 participants), 15 mg of tirzepatide 20.0% (18 out of 90 participants), Placebo 0% (0 out of 89 participants)] - Decreased appetite: 10 mg of tirzepatide 12.3% (9 out of 73 participants), 15 mg of tirzepatide 7.8% (6 out of 77 participants), Placebo 1.3% (1 out of 75 participants) [group before the exclusion: 10 mg of tirzepatide 10.2% (9 out of 88 participants), 15 mg of tirzepatide 6.7% (6 out of 90 participants), Placebo 1.1% (1 out of 89 participants)] - Diarrhea: 10 mg of tirzepatide 8.2% (6 out of 73 participants), 15 mg of tirzepatide 7.8% (6 out of 77 participants), Placebo 1.3% (1 out of 75 participants) [group before the exclusion: 10 mg of tirzepatide 6.8% (6 out of 88 participants), 15 mg of tirzepatide 7.8% (7 out of 90 participants), Placebo 1.1% (1 out of 89 participants)] - Vomiting: 10 mg of tirzepatide 4.1% (3 out of 73 participants), 15 mg of tirzepatide 9.1% (7 out of 77 participants), Placebo 0% (0 out of 75 participants) [group before the exclusion: 10 mg of tirzepatide 4.5% (4 out of 88 participants), 15 mg of tirzepatide 7.8% (7 out of 90 participants), Placebo 0% (0 out of 89 participants)] - Stomach area discomfort: 10 mg of tirzepatide 6.8% (5 out of 73 participants), 15 mg of tirzepatide 3.9% (3 out of 77 participants), Placebo 0% (0 out of 75 participants) [group before the exclusion: 10 mg of tirzepatide 6.8% (6 out of 88 participants), 15 mg of tirzepatide 3.3% (3 out of 90 participants), Placebo 0% (0 out of 89 participants)] - Reaction where the injection was given: 10 mg of tirzepatide 5.5% (4 out of 73 participants), 15 mg of tirzepatide 5.2% (4 out of 77 participants), Placebo 0% (0 out of 75 participants) (group before the exclusion: this was not the adverse event that was possibly related to the study treatment reported in 5.0% or more of participants in any of the groups)

This is a summary of the main results from this study overall. The results each participant had might be different from the overall summary results. A full list of the questions researchers wanted to answer can be found on the website listed at the end of this summary. If a full report of the study results is available, it can also be found on this website. It takes many studies to decide which treatments work best and are safest. Other studies may provide new information or different results. Did tirzepatide help the participants lose weight? Yes. Overall, after 72 weeks of treatment: - The participants who received tirzepatide lost more weight than the participants who received the placebo. - More participants who received tirzepatide lost at least 5.0% of their body weight compared to participants who received the placebo. To answer this question, the researchers measured the participants' body weight at every study site visit. Then the researchers compared the participants' body weight after they finished treatment (Week 72) to their body weight before starting treatment. The average change in the participants' body weight after 72 weeks of treatment with tirzepatide or the placebo is shown below: - The participants who received 10 mg of tirzepatide had a 17.8% decrease in their body weight (group before the exclusion: 18.3% decrease). - The participants who received 15 mg of tirzepatide had a 22.7% decrease in their body weight (group before the exclusion: 23.0% decrease). - The participants who received the placebo had a 1.7% decrease in their body weight (group before the exclusion: 1.5% decrease). The analysis results of percent change from baseline in body weight at Week 72 are shown below. Least squares (LS) mean was determined using mixed model repeated measures (MMRM) model with Baseline + impaired glucose tolerance (IGT) at Screening + Hyperlipidemia at Screening + non-alcoholic fatty liver disease (NAFLD) at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. All participants, excluding the GCP compliance investigative site, who received at least one dose of study drug and had evaluable data for this outcome were included in analysis Overall Number of Participants Analyzed - 10 mg Tirzepatide: 59 (group before the exclusion: 74) - 15 mg Tirzepatide: 65 (group before the exclusion: 76) - Placebo: 66 (group before the exclusion: 80) Least Squares Mean (Standard Error), Unit of Measure: Percent change - 10 mg Tirzepatide: -17.8 (0.94) [group before the exclusion: -18.3 (0.87)] - 15 mg Tirzepatide: -22.7 (0.90) [group before the exclusion: -23.0 (0.85)] - Placebo: -1.7 (0.90) [group before the exclusion: -1.5 (0.85)] LS Mean Difference (2-Sided 95% Confidence Interval) - 10 mg Tirzepatide, Placebo: -16.1 (-18.7 to -13.5) [group before the exclusion: -16.8 (-19.2 to -14.4)] - 15 mg Tirzepatide, Placebo: -21.1 (-23.6 to -18.5) [group before the exclusion: -21.5 (-23.8 to -19.1)] The researchers also compared the number of participants in each group whose body weight decreased by at least 5.0% by Week 72 of the study. The results of 3 participants could not be used for this part of the study, so the results below only contain 222 participants: - 94.4% of the participants who received 10 mg of tirzepatide had at least a 5.0% decrease in their body weight. This was 67 out of 71 participants (group before the exclusion: 94.2%, 81 out of 86 participants). - 96.1% of the participants who received 15 mg of tirzepatide had at least a 5.0% decrease in their body weight. This was 73 out of 76 participants (group before the exclusion: 97.8%, 87 out of 89 participants). - 20.0% of the participants who received the placebo had at least a 5.0% decrease in their body weight. This was 15 out of 75 participants (group before the exclusion: 18.0%, 16 out of 89 participants). The analysis results of percentage of participants who achieve >=5% body weight reduction from baseline at Week 72 are shown below. All participants, excluding the GCP compliance investigative site, who received at least one dose of study drug, had a baseline and at least one post-baseline value for this outcome were included in this analysis. Overall Number of Participants Analyzed - 10 mg Tirzepatide: 71 (group before the exclusion: 86) - 15 mg Tirzepatide: 76 (group before the exclusion: 89) - Placebo: 75 (group before the exclusion: 89) Percentage of participants who achieve >=5% body weight reduction - 10 mg Tirzepatide: 94.37 (group before the exclusion: 94.19) - 15 mg Tirzepatide: 96.05 (group before the exclusion: 97.75) - Placebo: 20 (group before the exclusion: 17.98) Odds Ratio (2-Sided 95% Confidence Interval) - 10 mg Tirzepatide, Placebo: 119.65 (29.06 to 492.67) [group after the exclusion: 93.23 (29.44 to 295.24)] - 15 mg Tirzepatide, Placebo: 153.57 (36.03 to 654.53) [group after the exclusion: 276.04 (56.84~1340.59)]

In this study, data from 225 Japanese participants with obesity disease were analyzed. Participants received tirzepatide or a placebo. Tirzepatide doses started at 2.5 mg, increasing to 10 mg or 15 mg over 20 weeks, then maintained until 72 weeks. For safety, adverse events possibly related to the study treatment were reported in 56.2% of the 10 mg group, 63.6% of the 15 mg group, and 10.7% of the placebo group. Tirzepatide 10 mg and 15 mg led to greater weight loss (17.8% and 22.7%) than placebo (1.7%).

https://www.clinicaltrials.gov/study/NCT04844918?term=GPHZ&rank=1

Yes

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210044

Masaki Takeshi

Eli Lilly Japan K.K.

5-1-28, Isogamidori, Chuo-ku, Kobe, Hyogo

LTG_CallCenter@lists.lilly.com

Trial Guide Call Center

Eli Lilly Japan K.K.

5-1-28, Isogamidori, Chuo-ku, Kobe, Hyogo

+81-120-023-812

LTG_CallCenter@lists.lilly.com

Complete

May. 10, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- Have a BMI of greater than or equal to >=27 kg/m2 and less than <35 kg/m2 with at least 2 obesity-related health problems or >=35 kg/m2 with at least 1 obesity-related health problems.
- Health problems are IGT, hyperlipidemia, or NAFLD.
- Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight.

- Have diabetes.
- Acute or chronic liver disease other than NAFLD.
- Have a self-reported change in body weight >5 kg within 3 months prior to screening.
- Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months.
- Have renal impairment measured as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, calculated by Japanese Society of Nephrology coefficient-modified Chronic Kidney Disease-Epidemiology equation during screening.
- Have a known clinically significant gastric emptying abnormality.
- Have had a history of chronic or acute pancreatitis.
- Have thyroid-stimulating hormone outside of the range of 0.4 to 6.0 micro units per milliliter (micro IU/mL) at screening.
- Have obesity induced by other endocrinologic disorders or diagnosed monogenetic or syndromic forms of obesity.
- Have a history of significant active or unstable major depressive disorder or other severe psychiatric disorder within the last 2 years.
- Have a cardiovascular condition within 3 months prior to randomization
- Have a family or personal history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome type 2.

Both

Obesity Disease

Tirzepatide Regimen A administered subcutaneously (SC)
Tirzepatide Regimen B administered SC
Placebo administered SC

1. Percentage of Participants Who Achieve >=5% Body Weight Reduction
2. Percent Change in Body Weight

+81-3-6262-2811

Jan. 15, 2021

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