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Clinical Trial Results:
A Phase 2 Study of Once-Daily LY3502970 Compared with Placebo in Participants Who Have Obesity or Are Overweight with Weight-Related Comorbidities

Summary
EudraCT number	2021-002805-88
Trial protocol	HU
Global end of trial date	22 Nov 2022

Results information
Results version number	v1(current)
This version publication date	08 Sep 2023
First version publication date	08 Sep 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

J2A-MC-GZGI

ISRCTN number

US NCT number

NCT05051579

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 18210

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

22 Nov 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 Nov 2022

Was the trial ended prematurely?

Main objective of the trial

The main purpose of the study was to assess the effect of LY3502970 in participants who have obesity or are overweight.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Sep 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 48

Country: Number of subjects enrolled

Hungary: 31

Country: Number of subjects enrolled

United States: 193

Worldwide total number of subjects

272

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

230

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

For maintenance doses of LY3502970: 12, 24, 36, and 45 milligram (mg), the initial dose will be 2 or 3 mg followed by additional escalation steps as appropriate. The dose-escalation varied by dose group where the target maintenance dose was achieved between Weeks 5 and 16.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

12 mg LY3502970

Arm description

Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks.

Arm type

Experimental

Investigational medicinal product name

12 mg LY3502970

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks.

24 mg LY3502970

Arm description

Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks.

Arm type

Experimental

Investigational medicinal product name

24 mg LY3502970

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks.

36 mg-1 LY3502970

Arm description

Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

Arm type

Experimental

Investigational medicinal product name

36 mg LY3502970

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

36 mg-2 LY3502970

Arm description

Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

Arm type

Experimental

Investigational medicinal product name

36 mg LY3502970

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

45 mg-1 LY3502970

Arm description

Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

Arm type

Experimental

Investigational medicinal product name

45 mg LY3502970

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

45 mg-2 LY3502970

Arm description

Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

Arm type

Experimental

Investigational medicinal product name

45 mg LY3502970

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

Placebo

Arm description

Participants received placebo administered orally once daily until 36 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received placebo administered orally once daily until 36 weeks.

Number of subjects in period 1	12 mg LY3502970	24 mg LY3502970	36 mg-1 LY3502970	36 mg-2 LY3502970	45 mg-1 LY3502970	45 mg-2 LY3502970	Placebo
Started	50	53	29	29	31	30	50
Completed	44	46	27	24	23	28	43
Not completed	6	7	2	5	8	2	7
Consent withdrawn by subject	3	5	2	1	4	-	4
Patient was Initially Long Term Follow-up But Cont	-	-	-	-	1	-	-
Adverse event, non-fatal	2	1	-	4	1	2	-
Sponsor Decision	-	-	-	-	1	-	-
Subject Unable to Visit Due to Working Out of Town	-	-	-	-	-	-	1
Lost to follow-up	1	-	-	-	1	-	1
Inadvertent Enrollment	-	-	-	-	-	-	1
Subject Could not Tolerate Investigational Product	-	1	-	-	-	-	-

Baseline characteristics

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Reporting group title

12 mg LY3502970

Reporting group description

Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

24 mg LY3502970

Reporting group description

Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

36 mg-1 LY3502970

Reporting group description

Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

36 mg-2 LY3502970

Reporting group description

Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

45 mg-1 LY3502970

Reporting group description

Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

45 mg-2 LY3502970

Reporting group description

Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

Placebo

Reporting group description

Participants received placebo administered orally once daily until 36 weeks.

Reporting group values	12 mg LY3502970	24 mg LY3502970	36 mg-1 LY3502970	36 mg-2 LY3502970	45 mg-1 LY3502970	45 mg-2 LY3502970	Placebo	Total
Number of subjects	50	53	29	29	31	30	50	272
Age categorical
Units: Subjects
Age continuous
All randomized participants.
Units: years
arithmetic mean (standard deviation)	49.80 ± 10.51	57.00 ± 9.09	56.30 ± 11.83	55.40 ± 10.93	56.50 ± 10.74	50.90 ± 12.58	54.00 ± 8.82	-
Gender categorical
All randomized participants.
Units: Subjects
Female	31	30	18	18	19	16	29	161
Male	19	23	11	11	12	14	21	111
Ethnicity (NIH/OMB)
All randomized participants.
Units: Subjects
Hispanic or Latino	11	6	4	2	4	7	5	39
Not Hispanic or Latino	38	46	23	26	25	22	43	223
Unknown or Not Reported	1	1	2	1	2	1	2	10
Race (NIH/OMB)
All randomized participants.
Units: Subjects
American Indian or Alaska Native	0	1	0	0	0	0	0	1
Asian	0	0	0	0	0	0	2	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0
Black or African American	3	6	4	4	1	0	1	19
White	47	46	25	25	29	30	45	247
More than one race	0	0	0	0	0	0	2	2
Unknown or Not Reported	0	0	0	0	1	0	0	1
Region of Enrollment
All randomized participants.
Units: Subjects
Canada	9	11	5	3	9	5	6	48
Hungary	6	5	3	6	3	3	5	31
United States	35	37	21	20	19	22	39	193
Baseline Body Weight
All randomized participants.
Units: Kilograms (kg)
arithmetic mean (standard deviation)	107.49 ± 25.34	112.05 ± 30.18	107.78 ± 22.45	108.84 ± 28.52	105.23 ± 20.40	110.85 ± 28.11	107.57 ± 25.24	-

End points

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Reporting group title

12 mg LY3502970

Reporting group description

Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

24 mg LY3502970

Reporting group description

Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

36 mg-1 LY3502970

Reporting group description

Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

36 mg-2 LY3502970

Reporting group description

Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

45 mg-1 LY3502970

Reporting group description

Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

45 mg-2 LY3502970

Reporting group description

Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

Placebo

Reporting group description

Participants received placebo administered orally once daily until 36 weeks.

Subject analysis set title

36 mg LY3502970

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks.

Subject analysis set title

45 mg LY3502970

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks.

Subject analysis set title

Placebo

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Participants received placebo administered orally once daily until 36 weeks.

Primary: Percent Change from Baseline in Body Weight in LY3502970 and Placebo

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End point title

Percent Change from Baseline in Body Weight in LY3502970 and Placebo ^[1]

End point description

Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. Analysis population of description (APD) included all randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline body weight value.

End point type

Primary

End point timeframe

Baseline, Week 26

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: Percent change
least squares mean (standard error)	-8.6 ± 0.85	-11.2 ± 0.82	-12.3 ± 0.77	-12.6 ± 0.75	-2.0 ± 0.81

Percent Change from Baseline in Body Weight

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-6.5

Confidence interval

level

95%

sides

2-sided

lower limit

-8.9

upper limit

-4.2

Percent Change from Baseline in Body Weight

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-9.2

Confidence interval

level

95%

sides

2-sided

lower limit

-11.5

upper limit

-6.9

Percent Change from Baseline in Body Weight

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-10.2

Confidence interval

level

95%

sides

2-sided

lower limit

-12.4

upper limit

-8

Percent Change from Baseline in Body Weight

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-10.6

Confidence interval

level

95%

sides

2-sided

lower limit

-12.7

upper limit

-8.4

Secondary: Percent Change from Baseline in Body Weight in LY3502970 and Placebo

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End point title

Percent Change from Baseline in Body Weight in LY3502970 and Placebo ^[2]

End point description

LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. APD included all randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline body weight value.

End point type

Secondary

End point timeframe

Baseline, Week 36

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: Percent change
least squares mean (standard error)	-9.4 ± 1.05	-12.5 ± 1.01	-13.5 ± 0.95	-14.7 ± 0.94	-2.3 ± 1.00

Percent Change from Baseline in Body Weight

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-7.1

Confidence interval

level

95%

sides

2-sided

lower limit

-9.9

upper limit

-4.2

Percent Change from Baseline in Body Weight

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-10.1

Confidence interval

level

95%

sides

2-sided

lower limit

-12.9

upper limit

-7.3

Percent Change from Baseline in Body Weight

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-11.1

Confidence interval

level

95%

sides

2-sided

lower limit

-13.8

upper limit

-8.4

Percent Change from Baseline in Body Weight

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-12.3

Confidence interval

level

95%

sides

2-sided

lower limit

-15

upper limit

-9.6

Secondary: Change from Baseline in Body Weight in LY3502970 and Placebo

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End point title

Change from Baseline in Body Weight in LY3502970 and Placebo ^[3]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 26

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: kg
least squares mean (standard error)	-9.0 ± 0.90	-12.3 ± 0.86	-12.9 ± 0.82	-13.3 ± 0.79	-2.1 ± 0.86

Change from Baseline in Body Weight in LY3502970

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-6.9

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

-4.4

Change from Baseline in Body Weight in LY3502970

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-10.2

Confidence interval

level

95%

sides

2-sided

lower limit

-12.5

upper limit

-7.8

Change from Baseline in Body Weight in LY3502970

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-13.1

upper limit

-8.5

Change from Baseline in Body Weight in LY3502970

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-11.2

Confidence interval

level

95%

sides

2-sided

lower limit

-13.5

upper limit

-8.9

Secondary: Change From Baseline in Body Weight in LY3502970 and Placebo

Top of page

End point title

Change From Baseline in Body Weight in LY3502970 and Placebo ^[4]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 36

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: kg
least squares mean (standard error)	-9.8 ± 1.10	-13.6 ± 1.06	-14.2 ± 1.00	-15.4 ± 0.98	-2.4 ± 1.05

Change From Baseline in Body Weight

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-7.4

Confidence interval

level

95%

sides

2-sided

lower limit

-10.4

upper limit

-4.3

Change From Baseline in Body Weight

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-11.2

Confidence interval

level

95%

sides

2-sided

lower limit

-14.2

upper limit

-8.3

Change From Baseline in Body Weight

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-11.8

Confidence interval

level

95%

sides

2-sided

lower limit

-14.7

upper limit

-9

Change From Baseline in Body Weight

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-13

Confidence interval

level

95%

sides

2-sided

lower limit

-15.8

upper limit

-10.2

Secondary: Change from Baseline in Waist Circumference in LY3502970 and Placebo

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End point title

Change from Baseline in Waist Circumference in LY3502970 and Placebo ^[5]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 26

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	43	49	52	57	48
Units: centimeter (cm)
least squares mean (standard error)	-8.0 ± 1.03	-8.8 ± 1.00	-10.1 ± 0.94	-12.2 ± 0.93	-3.6 ± 0.99

Change from Baseline in Waist Circumference

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.002

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-4.4

Confidence interval

level

95%

sides

2-sided

lower limit

-7.2

upper limit

-1.6

Change from Baseline in Waist Circumference

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

-2.4

Change from Baseline in Waist Circumference

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-6.5

Confidence interval

level

95%

sides

2-sided

lower limit

-9.2

upper limit

-3.8

Change from Baseline in Waist Circumference

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-11.3

upper limit

-6

Secondary: Change From Baseline in Waist Circumference in LY3502970 and Placebo

Top of page

End point title

Change From Baseline in Waist Circumference in LY3502970 and Placebo ^[6]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 36

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	43	49	52	57	48
Units: cm
least squares mean (standard error)	-9.6 ± 1.18	-11.2 ± 1.15	-10.6 ± 1.06	-13.6 ± 1.07	-4.0 ± 1.12

Change From Baseline in Waist Circumference

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-5.6

Confidence interval

level

95%

sides

2-sided

lower limit

-8.8

upper limit

-2.4

Change From Baseline in Waist Circumference

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-7.2

Confidence interval

level

95%

sides

2-sided

lower limit

-10.3

upper limit

-4

Change From Baseline in Waist Circumference

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-6.6

Confidence interval

level

95%

sides

2-sided

lower limit

-9.7

upper limit

-3.6

Change From Baseline in Waist Circumference

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-9.6

Confidence interval

level

95%

sides

2-sided

lower limit

-12.7

upper limit

-6.6

Secondary: Change from Baseline in BMI in LY3502970 and Placebo

Top of page

End point title

Change from Baseline in BMI in LY3502970 and Placebo ^[7]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 26

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: kilograms per meter square (kg/m^2)
least squares mean (standard error)	-3.2 ± 0.21	-4.2 ± 0.30	-4.6 ± 0.28	-4.7 ± 0.27	-0.8 ± 0.29

Change from Baseline in BMI

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

-1.6

Change from Baseline in BMI

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

-2.6

Change from Baseline in BMI

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

Change from Baseline in BMI

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-4.7

upper limit

-3.1

Secondary: Change From Baseline in BMI in LY3502970 and Placebo

Top of page

End point title

Change From Baseline in BMI in LY3502970 and Placebo ^[8]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 36

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: kg/m^2
least squares mean (standard error)	-3.4 ± 0.38	-4.7 ± 0.36	-5.0 ± 0.34	-5.5 ± 0.34	-0.9 ± 0.36

Change From Baseline in BMI

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

-1.5

Change From Baseline in BMI

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

-2.8

Change From Baseline in BMI

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

-3.2

Change From Baseline in BMI

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5.6

upper limit

-3.6

Secondary: Percentage of Participants with >=5% Body Weight Loss

Top of page

End point title

Percentage of Participants with >=5% Body Weight Loss ^[9]

End point description

Percentage of participants with >=5% body weight loss was reported. APD included all randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥5% body weight reduction.

End point type

Secondary

End point timeframe

Week 26

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: percentage of participants
number (not applicable)	74.39	88.84	89.46	87.26	22.88

Percentage of Participants with >=5% Body Weight

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

9.96

Confidence interval

level

95%

sides

2-sided

lower limit

3.61

upper limit

27.44

Percentage of Participants with >=5% Body Weight

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

27.97

Confidence interval

level

95%

sides

2-sided

lower limit

8.15

upper limit

96.01

Percentage of Participants with >=5% Body Weight

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

27.36

Confidence interval

level

95%

sides

2-sided

lower limit

8.71

upper limit

85.91

Percentage of Participants with >=5% Body Weight

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

23.59

Confidence interval

level

95%

sides

2-sided

lower limit

7.65

upper limit

72.77

Secondary: Percentage of Participants with >=10% Body Weight Loss

Top of page

End point title

Percentage of Participants with >=10% Body Weight Loss ^[10]

End point description

Percentage of participants with >=10% body weight loss was reported. APD included all randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥10% body weight reduction.

End point type

Secondary

End point timeframe

Week 26

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: percentage of participants
number (not applicable)	39.39	56.61	71.30	69.86	2.25

Percentage of Participants with >=10% Body Weight

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

19.93

Confidence interval

level

95%

sides

2-sided

lower limit

3.47

upper limit

114.4

Percentage of Participants with >=10% Body Weight

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

39.52

Confidence interval

level

95%

sides

2-sided

lower limit

6.95

upper limit

224.83

Percentage of Participants with >=10% Body Weight

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

74.97

Confidence interval

level

95%

sides

2-sided

lower limit

13.16

upper limit

427.18

Percentage of Participants with >=10% Body Weight

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

72.23

Confidence interval

level

95%

sides

2-sided

lower limit

12.62

upper limit

413.21

Secondary: Percentage of Participants with >=5% Body Weight Loss

Top of page

End point title

Percentage of Participants with >=5% Body Weight Loss ^[11]

End point description

End point type

Secondary

End point timeframe

Week 36

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: percentage of participants
number (not applicable)	72.00	89.47	92.05	90.44	24.02

Percentage of Participants with >=5% Body Weight

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.79

Confidence interval

level

95%

sides

2-sided

lower limit

2.9

upper limit

20.92

Percentage of Participants with >=5% Body Weight

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

25.07

Confidence interval

level

95%

sides

2-sided

lower limit

7.49

upper limit

83.91

Percentage of Participants with >=5% Body Weight

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

34.76

Confidence interval

level

95%

sides

2-sided

lower limit

8.17

upper limit

147.86

Percentage of Participants with >=5% Body Weight

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

28.01

Confidence interval

level

95%

sides

2-sided

lower limit

8.15

upper limit

96.29

Secondary: Percentage of Participants with >=10% Body Weight Loss

Top of page

End point title

Percentage of Participants with >=10% Body Weight Loss ^[12]

End point description

End point type

Secondary

End point timeframe

Week 36

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics was added in baseline period reporting arms, subject analysis set with evaluable endpoint data.

End point values	12 mg LY3502970	24 mg LY3502970	36 mg LY3502970	45 mg LY3502970	Placebo
Number of subjects analysed	44	51	56	57	48
Units: percentage of participants
number (not applicable)	46.50	61.88	74.75	69.07	8.85

Percentage of Participants with >=10% Body Weight

Comparison groups

12 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

8.27

Confidence interval

level

95%

sides

2-sided

lower limit

2.59

upper limit

26.45

Percentage of Participants with >=10% Body Weight

Comparison groups

24 mg LY3502970 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

15.64

Confidence interval

level

95%

sides

2-sided

lower limit

4.83

upper limit

50.68

Percentage of Participants with >=10% Body Weight

Comparison groups

36 mg LY3502970 v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

27.24

Confidence interval

level

95%

sides

2-sided

lower limit

8.39

upper limit

88.38

Percentage of Participants with >=10% Body Weight

Comparison groups

45 mg LY3502970 v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

20.88

Confidence interval

level

95%

sides

2-sided

lower limit

6.59

upper limit

66.17

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline through Week 38 (36 weeks follow up with 2 weeks safety follow up)

Adverse event reporting additional description

All randomized participants who received at least one dose of study drug regardless of adherence to study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

Placebo

Reporting group description

Participants received placebo administered orally once daily until 36 weeks.

Reporting group title

12 mg LY3502970

Reporting group description

Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

24 mg LY3502970

Reporting group description

Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

45 mg-2 LY3502970

Reporting group description

Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

36 mg-2 LY3502970

Reporting group description

Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

45 mg-1 LY3502970

Reporting group description

Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks.

Reporting group title

36 mg-1 LY3502970

Reporting group description

Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks.

Serious adverse events	Placebo	12 mg LY3502970	24 mg LY3502970	45 mg-2 LY3502970	36 mg-2 LY3502970	45 mg-1 LY3502970	36 mg-1 LY3502970
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	2 / 53 (3.77%)	0 / 30 (0.00%)	3 / 29 (10.34%)	2 / 31 (6.45%)	0 / 29 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
hepatic cancer metastatic
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	0 / 30 (0.00%)	1 / 29 (3.45%)	0 / 31 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
coronary artery disease
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	0 / 30 (0.00%)	0 / 29 (0.00%)	1 / 31 (3.23%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
retinal vein thrombosis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	0 / 30 (0.00%)	1 / 29 (3.45%)	0 / 31 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
vitreoretinal traction syndrome
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	0 / 30 (0.00%)	0 / 29 (0.00%)	1 / 31 (3.23%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
diverticulum intestinal
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	0 / 30 (0.00%)	1 / 29 (3.45%)	0 / 31 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
gastrointestinal polyp haemorrhage
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 53 (1.89%)	0 / 30 (0.00%)	0 / 29 (0.00%)	0 / 31 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
cholecystitis acute
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 53 (1.89%)	0 / 30 (0.00%)	0 / 29 (0.00%)	0 / 31 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
hypercalcaemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	0 / 30 (0.00%)	1 / 29 (3.45%)	0 / 31 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	12 mg LY3502970	24 mg LY3502970	45 mg-2 LY3502970	36 mg-2 LY3502970	45 mg-1 LY3502970	36 mg-1 LY3502970
Total subjects affected by non serious adverse events
subjects affected / exposed	27 / 50 (54.00%)	35 / 50 (70.00%)	46 / 53 (86.79%)	24 / 30 (80.00%)	25 / 29 (86.21%)	26 / 31 (83.87%)	23 / 29 (79.31%)
Vascular disorders
hypotension
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	3 / 30 (10.00%)	0 / 29 (0.00%)	1 / 31 (3.23%)	2 / 29 (6.90%)
occurrences all number	0	0	0	3	0	1	2
Cardiac disorders
atrioventricular block first degree
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	3 / 30 (10.00%)	0 / 29 (0.00%)	0 / 31 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	0	3	0	0	0
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	5 / 50 (10.00%)	2 / 53 (3.77%)	4 / 30 (13.33%)	1 / 29 (3.45%)	2 / 31 (6.45%)	1 / 29 (3.45%)
occurrences all number	1	5	3	4	1	2	1
headache
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	5 / 50 (10.00%)	4 / 50 (8.00%)	8 / 53 (15.09%)	2 / 30 (6.67%)	2 / 29 (6.90%)	4 / 31 (12.90%)	3 / 29 (10.34%)
occurrences all number	7	4	11	3	2	6	3
General disorders and administration site conditions
chills
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	1 / 50 (2.00%)	1 / 53 (1.89%)	0 / 30 (0.00%)	0 / 29 (0.00%)	2 / 31 (6.45%)	1 / 29 (3.45%)
occurrences all number	0	1	1	0	0	2	1
fatigue
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	2 / 50 (4.00%)	7 / 53 (13.21%)	4 / 30 (13.33%)	2 / 29 (6.90%)	4 / 31 (12.90%)	4 / 29 (13.79%)
occurrences all number	1	2	8	6	2	5	4
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 50 (4.00%)	4 / 50 (8.00%)	4 / 53 (7.55%)	1 / 30 (3.33%)	2 / 29 (6.90%)	2 / 31 (6.45%)	0 / 29 (0.00%)
occurrences all number	2	4	5	3	2	2	0
abdominal discomfort
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	0 / 50 (0.00%)	4 / 53 (7.55%)	0 / 30 (0.00%)	1 / 29 (3.45%)	4 / 31 (12.90%)	1 / 29 (3.45%)
occurrences all number	1	0	4	0	1	4	1
abdominal distension
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	1 / 50 (2.00%)	4 / 53 (7.55%)	2 / 30 (6.67%)	1 / 29 (3.45%)	1 / 31 (3.23%)	0 / 29 (0.00%)
occurrences all number	1	1	5	2	1	1	0
abdominal pain upper
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	1 / 50 (2.00%)	3 / 53 (5.66%)	3 / 30 (10.00%)	2 / 29 (6.90%)	0 / 31 (0.00%)	0 / 29 (0.00%)
occurrences all number	1	1	3	3	2	0	0
dyspepsia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 50 (6.00%)	8 / 50 (16.00%)	4 / 53 (7.55%)	2 / 30 (6.67%)	1 / 29 (3.45%)	3 / 31 (9.68%)	1 / 29 (3.45%)
occurrences all number	4	11	4	2	1	3	1
diarrhoea
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	5 / 50 (10.00%)	12 / 50 (24.00%)	19 / 53 (35.85%)	10 / 30 (33.33%)	4 / 29 (13.79%)	5 / 31 (16.13%)	1 / 29 (3.45%)
occurrences all number	6	23	29	16	5	5	1
constipation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 50 (6.00%)	12 / 50 (24.00%)	17 / 53 (32.08%)	4 / 30 (13.33%)	7 / 29 (24.14%)	6 / 31 (19.35%)	8 / 29 (27.59%)
occurrences all number	3	16	21	5	10	8	8
gastrooesophageal reflux disease
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	4 / 50 (8.00%)	5 / 53 (9.43%)	2 / 30 (6.67%)	4 / 29 (13.79%)	4 / 31 (12.90%)	3 / 29 (10.34%)
occurrences all number	1	4	6	2	5	6	3
flatulence
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 50 (4.00%)	0 / 50 (0.00%)	3 / 53 (5.66%)	0 / 30 (0.00%)	1 / 29 (3.45%)	1 / 31 (3.23%)	0 / 29 (0.00%)
occurrences all number	2	0	3	0	1	1	0
eructation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	9 / 50 (18.00%)	11 / 53 (20.75%)	6 / 30 (20.00%)	2 / 29 (6.90%)	2 / 31 (6.45%)	5 / 29 (17.24%)
occurrences all number	0	15	14	9	2	2	5
vomiting
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 50 (6.00%)	13 / 50 (26.00%)	17 / 53 (32.08%)	8 / 30 (26.67%)	4 / 29 (13.79%)	9 / 31 (29.03%)	8 / 29 (27.59%)
occurrences all number	3	23	33	15	9	14	11
nausea
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	5 / 50 (10.00%)	25 / 50 (50.00%)	31 / 53 (58.49%)	11 / 30 (36.67%)	14 / 29 (48.28%)	13 / 31 (41.94%)	12 / 29 (41.38%)
occurrences all number	6	39	50	23	18	28	18
Reproductive system and breast disorders
balanoposthitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[1]	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 23 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	1
erectile dysfunction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[2]	0 / 21 (0.00%)	1 / 19 (5.26%)	0 / 23 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0
postmenopausal haemorrhage
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[3]	0 / 29 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 19 (5.26%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	1	0
vulvovaginal pruritus
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[4]	0 / 29 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 19 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
oropharyngeal pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	1 / 30 (3.33%)	2 / 29 (6.90%)	0 / 31 (0.00%)	0 / 29 (0.00%)
occurrences all number	2	0	0	1	2	0	0
Skin and subcutaneous tissue disorders
alopecia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	1 / 50 (2.00%)	1 / 53 (1.89%)	0 / 30 (0.00%)	0 / 29 (0.00%)	3 / 31 (9.68%)	0 / 29 (0.00%)
occurrences all number	1	1	1	0	0	3	0
Renal and urinary disorders
dysuria
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)	0 / 30 (0.00%)	1 / 29 (3.45%)	1 / 31 (3.23%)	2 / 29 (6.90%)
occurrences all number	0	0	0	0	1	1	3
Musculoskeletal and connective tissue disorders
back pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	4 / 50 (8.00%)	1 / 50 (2.00%)	2 / 53 (3.77%)	1 / 30 (3.33%)	1 / 29 (3.45%)	1 / 31 (3.23%)	1 / 29 (3.45%)
occurrences all number	4	1	2	1	1	1	1
arthralgia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	1 / 50 (2.00%)	5 / 53 (9.43%)	1 / 30 (3.33%)	1 / 29 (3.45%)	1 / 31 (3.23%)	1 / 29 (3.45%)
occurrences all number	1	1	5	1	1	2	1
myalgia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	0 / 50 (0.00%)	1 / 53 (1.89%)	0 / 30 (0.00%)	0 / 29 (0.00%)	0 / 31 (0.00%)	3 / 29 (10.34%)
occurrences all number	1	0	1	0	0	0	3
muscle spasms
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 53 (1.89%)	2 / 30 (6.67%)	0 / 29 (0.00%)	1 / 31 (3.23%)	1 / 29 (3.45%)
occurrences all number	0	0	1	2	0	1	1
pain in extremity
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	1 / 50 (2.00%)	1 / 53 (1.89%)	0 / 30 (0.00%)	2 / 29 (6.90%)	0 / 31 (0.00%)	1 / 29 (3.45%)
occurrences all number	1	1	1	0	2	0	1
Infections and infestations
covid-19
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	9 / 50 (18.00%)	9 / 50 (18.00%)	9 / 53 (16.98%)	5 / 30 (16.67%)	7 / 29 (24.14%)	5 / 31 (16.13%)	4 / 29 (13.79%)
occurrences all number	9	11	9	5	7	5	4
nasopharyngitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 50 (0.00%)	1 / 50 (2.00%)	2 / 53 (3.77%)	2 / 30 (6.67%)	0 / 29 (0.00%)	1 / 31 (3.23%)	0 / 29 (0.00%)
occurrences all number	0	2	2	2	0	1	0
urinary tract infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 50 (6.00%)	2 / 50 (4.00%)	3 / 53 (5.66%)	2 / 30 (6.67%)	3 / 29 (10.34%)	1 / 31 (3.23%)	0 / 29 (0.00%)
occurrences all number	3	2	4	2	3	1	0
upper respiratory tract infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	3 / 50 (6.00%)	0 / 53 (0.00%)	2 / 30 (6.67%)	1 / 29 (3.45%)	1 / 31 (3.23%)	2 / 29 (6.90%)
occurrences all number	1	3	0	2	1	1	3
sinusitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	1 / 50 (2.00%)	3 / 53 (5.66%)	2 / 30 (6.67%)	0 / 29 (0.00%)	0 / 31 (0.00%)	1 / 29 (3.45%)
occurrences all number	1	1	3	2	0	0	2
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 50 (2.00%)	4 / 50 (8.00%)	4 / 53 (7.55%)	2 / 30 (6.67%)	1 / 29 (3.45%)	3 / 31 (9.68%)	0 / 29 (0.00%)
occurrences all number	1	4	5	2	1	3	0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.

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Were there any global substantial amendments to the protocol? Yes

27 Sep 2021

Modified schedule of activities; - Objectives, overview of study periods and exclusion criteria were updated; - Provided additional guidance on Concomitant therapy; - Clarified QTc stopping criteria; - Changed wording regarding restarting study drug through IWRS; - Removed ABPM measurements and lipids measurements from exploratory efficacy assessments; - Statistical analysis general considerations were modified.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 2 Study of Once-Daily LY3502970 Compared with Placebo in Participants Who Have Obesity or Are Overweight with Weight-Related Comorbidities

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent Change from Baseline in Body Weight in LY3502970 and Placebo

Primary: Percent Change from Baseline in Body Weight in LY3502970 and Placebo

Secondary: Percent Change from Baseline in Body Weight in LY3502970 and Placebo

Secondary: Percent Change from Baseline in Body Weight in LY3502970 and Placebo

Secondary: Change from Baseline in Body Weight in LY3502970 and Placebo

Secondary: Change from Baseline in Body Weight in LY3502970 and Placebo

Secondary: Change From Baseline in Body Weight in LY3502970 and Placebo

Secondary: Change From Baseline in Body Weight in LY3502970 and Placebo

Secondary: Change from Baseline in Waist Circumference in LY3502970 and Placebo

Secondary: Change from Baseline in Waist Circumference in LY3502970 and Placebo

Secondary: Change From Baseline in Waist Circumference in LY3502970 and Placebo

Secondary: Change From Baseline in Waist Circumference in LY3502970 and Placebo

Secondary: Change from Baseline in BMI in LY3502970 and Placebo

Secondary: Change from Baseline in BMI in LY3502970 and Placebo

Secondary: Change From Baseline in BMI in LY3502970 and Placebo

Secondary: Change From Baseline in BMI in LY3502970 and Placebo

Secondary: Percentage of Participants with >=5% Body Weight Loss

Secondary: Percentage of Participants with >=5% Body Weight Loss

Secondary: Percentage of Participants with >=10% Body Weight Loss

Secondary: Percentage of Participants with >=10% Body Weight Loss

Secondary: Percentage of Participants with >=5% Body Weight Loss

Secondary: Percentage of Participants with >=5% Body Weight Loss

Secondary: Percentage of Participants with >=10% Body Weight Loss

Secondary: Percentage of Participants with >=10% Body Weight Loss

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2 Study of Once-Daily LY3502970 Compared with Placebo in Participants Who Have Obesity or Are Overweight with Weight-Related Comorbidities