Trial Outcomes & Findings for A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes (NCT NCT03311724)

Last Updated: 2021-05-19

Results Overview

Least squares (LS) mean was calculated using mixed model repeated measures model (MMRM) with baseline + baseline BMI group + baseline metformin flag + treatment + time + treatment\*time as fixed factors.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

111 participants

Primary outcome timeframe

Baseline, 3 Months

Results posted on

2021-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received Placebo by subcutaneous (SC) injection.	4, 8 and 12mg Tirzepatide Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Overall Study STARTED	26	29	28	28
Overall Study Received At Least One Dose of Study Drug	26	29	28	28
Overall Study Completed Treatment	20	27	22	26
Overall Study COMPLETED	23	28	26	27
Overall Study NOT COMPLETED	3	1	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received Placebo by subcutaneous (SC) injection.	4, 8 and 12mg Tirzepatide Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Overall Study Physician Decision	0	0	0	1
Overall Study Protocol Violation	1	0	1	0
Overall Study Withdrawal by Subject	1	1	0	0
Overall Study Lost to Follow-up	1	0	0	0
Overall Study Sponsor Decision	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=26 Participants Placebo administered by SC injection.	4, 8 and 12mg Tirzepatide n=29 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=28 Participants Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=28 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.	Total n=111 Participants Total of all reporting groups
Age, Continuous	56.0 years STANDARD_DEVIATION 10.13 • n=99 Participants	61.2 years STANDARD_DEVIATION 7.56 • n=107 Participants	55.5 years STANDARD_DEVIATION 8.54 • n=206 Participants	56.6 years STANDARD_DEVIATION 9.21 • n=7 Participants	57.4 years STANDARD_DEVIATION 9.06 • n=31 Participants
Sex: Female, Male Female	14 Participants n=99 Participants	14 Participants n=107 Participants	12 Participants n=206 Participants	5 Participants n=7 Participants	45 Participants n=31 Participants
Sex: Female, Male Male	12 Participants n=99 Participants	15 Participants n=107 Participants	16 Participants n=206 Participants	23 Participants n=7 Participants	66 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=99 Participants	15 Participants n=107 Participants	14 Participants n=206 Participants	14 Participants n=7 Participants	59 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=99 Participants	14 Participants n=107 Participants	14 Participants n=206 Participants	14 Participants n=7 Participants	52 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	3 Participants n=31 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	1 Participants n=7 Participants	4 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	7 Participants n=107 Participants	5 Participants n=206 Participants	2 Participants n=7 Participants	15 Participants n=31 Participants
Race (NIH/OMB) White	25 Participants n=99 Participants	19 Participants n=107 Participants	20 Participants n=206 Participants	23 Participants n=7 Participants	87 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants	2 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Region of Enrollment United States	26 Participants n=99 Participants	29 Participants n=107 Participants	28 Participants n=206 Participants	28 Participants n=7 Participants	111 Participants n=31 Participants
Hemoglobin A1c (HbA1c)	8.23 Percentage of HbA1C STANDARD_DEVIATION 1.22 • n=99 Participants	8.35 Percentage of HbA1C STANDARD_DEVIATION 0.897 • n=107 Participants	8.48 Percentage of HbA1C STANDARD_DEVIATION 1.171 • n=206 Participants	8.35 Percentage of HbA1C STANDARD_DEVIATION 1.12 • n=7 Participants	8.35 Percentage of HbA1C STANDARD_DEVIATION 1.094 • n=31 Participants
Fasting Blood Glucose (FBG)	9.68 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.44 • n=99 Participants	9.76 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.03 • n=107 Participants	10.40 millimoles per liter (mmol/L) STANDARD_DEVIATION 4.04 • n=206 Participants	10.67 millimoles per liter (mmol/L) STANDARD_DEVIATION 4.22 • n=7 Participants	10.13 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.69 • n=31 Participants
Body Weight	89.58 kilogram (kg) STANDARD_DEVIATION 23.69 • n=99 Participants	87.98 kilogram (kg) STANDARD_DEVIATION 17.35 • n=107 Participants	88.74 kilogram (kg) STANDARD_DEVIATION 18.21 • n=206 Participants	89.59 kilogram (kg) STANDARD_DEVIATION 16.91 • n=7 Participants	88.95 kilogram (kg) STANDARD_DEVIATION 18.87 • n=31 Participants
Waist Circumference	109.09 centimeter (cm) STANDARD_DEVIATION 15.38 • n=99 Participants	107.65 centimeter (cm) STANDARD_DEVIATION 12.22 • n=107 Participants	107.02 centimeter (cm) STANDARD_DEVIATION 12.64 • n=206 Participants	105.10 centimeter (cm) STANDARD_DEVIATION 12.19 • n=7 Participants	107.19 centimeter (cm) STANDARD_DEVIATION 13.02 • n=31 Participants

PRIMARY outcome

Timeframe: Baseline, 3 Months

Population: All participants who received at least 1 dose of study drug and had baseline and at least one post baseline data. Participants who discontinued study drug or initiated rescue drug were excluded.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo administered SC.	4, 8 and 12mg Tirzepatide n=27 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=23 Participants Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=26 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Change From Baseline in Haemoglobin A1c (HbA1c)	0.2 Percentage of HbA1C Standard Error 0.21	-1.7 Percentage of HbA1C Standard Error 0.19	-2.0 Percentage of HbA1C Standard Error 0.20	-1.8 Percentage of HbA1C Standard Error 0.19

SECONDARY outcome

Timeframe: 3 Months

Percentage of participants achieving HbA1c target of \< (less than) 7.0%.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo administered SC.	4, 8 and 12mg Tirzepatide n=27 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=23 Participants Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=26 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Percentage of Participants Achieving HbA1c Target of <7.0%	10 percentage of participants	74.1 percentage of participants	87 percentage of participants	84.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 3 Months

LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment\*time as fixed factors.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo administered SC.	4, 8 and 12mg Tirzepatide n=27 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=23 Participants Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=25 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Change From Baseline in Fasting Blood Glucose (FBG)	-12.3 milligrams per deciliter (mg/dL) Standard Error 9.27	-60.7 milligrams per deciliter (mg/dL) Standard Error 8.21	-70.2 milligrams per deciliter (mg/dL) Standard Error 8.72	-74.2 milligrams per deciliter (mg/dL) Standard Error 8.67

SECONDARY outcome

Timeframe: Baseline, 3 Months

LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment\*time as fixed factors.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo administered SC.	4, 8 and 12mg Tirzepatide n=27 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=23 Participants Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=26 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Change From Baseline in Body Weight	-0.5 kilogram (kg) Standard Error 0.86	-5.3 kilogram (kg) Standard Error 0.78	-5.5 kilogram (kg) Standard Error 0.80	-5.7 kilogram (kg) Standard Error 0.79

SECONDARY outcome

Timeframe: Baseline, 3 Months

LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment\*time as fixed factors.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo administered SC.	4, 8 and 12mg Tirzepatide n=27 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=23 Participants Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=26 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Change From Baseline in Waist Circumference	-2.5 centimeter (cm) Standard Error 1.01	-4.8 centimeter (cm) Standard Error 0.90	-4.9 centimeter (cm) Standard Error 0.94	-4.9 centimeter (cm) Standard Error 0.93

SECONDARY outcome

Timeframe: Baseline through 3 Months

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

Number of participants with anti drug antibodies.

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Placebo administered SC.	4, 8 and 12mg Tirzepatide n=29 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=28 Participants Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=27 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Number of Participants With Anti Drug Antibodies	0 participants	10 participants	8 participants	4 participants

SECONDARY outcome

Timeframe: Baseline through 3 Months

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

Number of episodes of total hypoglycemia episodes with plasma glucose \<= ( less than or equal to) 54 mg/dL.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Placebo administered SC.	4, 8 and 12mg Tirzepatide n=29 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=28 Participants Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=28 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Number of Episodes of Total Hypoglycemia Episodes	0 Episodes	0 Episodes	0 Episodes	1 Episodes

SECONDARY outcome

Timeframe: Week 4, 8 12: Pre-dose

Population: All randomized participants who received at least one dose of study drug and had evaluable PK samples.

Pharmacokinetics (PK): Average Trough Concentration (Conctrough) of Tirzepatide.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Placebo administered SC.	4, 8 and 12mg Tirzepatide n=28 Participants Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=28 Participants Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Pharmacokinetics (PK): Average Trough Concentration (Conctrough) of Tirzepatide	508 nanograms per milliliter (ng/mL) Standard Deviation 366	704 nanograms per milliliter (ng/mL) Standard Deviation 518	630 nanograms per milliliter (ng/mL) Standard Deviation 414	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

4, 8 and 12mg Tirzepatide

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

2.5, 5, 10, and 15mg Tirzepatide

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

2.5, 7.5 and 15mg Tirzepatide

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=26 participants at risk Placebo administered SC	4, 8 and 12mg Tirzepatide n=29 participants at risk Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=28 participants at risk Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=28 participants at risk Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.4% 1/29 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Investigations White blood cell count increased	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.4% 1/29 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Placebo n=26 participants at risk Placebo administered SC	4, 8 and 12mg Tirzepatide n=29 participants at risk Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.	2.5, 5, 10, and 15mg Tirzepatide n=28 participants at risk Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.	2.5, 7.5 and 15mg Tirzepatide n=28 participants at risk Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
Gastrointestinal disorders Abdominal distension	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/29 • Baseline through end of study (Up to 15 weeks). All randomized participants.	10.7% 3/28 • Number of events 9 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Abdominal pain	3.8% 1/26 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.4% 1/29 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	17.9% 5/28 • Number of events 5 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.6% 1/28 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	6.9% 2/29 • Number of events 3 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.6% 1/28 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 4 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Constipation	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.4% 1/29 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	10.7% 3/28 • Number of events 5 • Baseline through end of study (Up to 15 weeks). All randomized participants.	17.9% 5/28 • Number of events 5 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Diarrhoea	7.7% 2/26 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	31.0% 9/29 • Number of events 18 • Baseline through end of study (Up to 15 weeks). All randomized participants.	35.7% 10/28 • Number of events 19 • Baseline through end of study (Up to 15 weeks). All randomized participants.	32.1% 9/28 • Number of events 19 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Dyspepsia	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	17.2% 5/29 • Number of events 7 • Baseline through end of study (Up to 15 weeks). All randomized participants.	10.7% 3/28 • Number of events 12 • Baseline through end of study (Up to 15 weeks). All randomized participants.	10.7% 3/28 • Number of events 3 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Eructation	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	6.9% 2/29 • Number of events 3 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Flatulence	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.4% 1/29 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 3 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 3 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	6.9% 2/29 • Number of events 3 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.6% 1/28 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Nausea	7.7% 2/26 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	24.1% 7/29 • Number of events 14 • Baseline through end of study (Up to 15 weeks). All randomized participants.	39.3% 11/28 • Number of events 18 • Baseline through end of study (Up to 15 weeks). All randomized participants.	35.7% 10/28 • Number of events 16 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Gastrointestinal disorders Vomiting	3.8% 1/26 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	17.2% 5/29 • Number of events 6 • Baseline through end of study (Up to 15 weeks). All randomized participants.	17.9% 5/28 • Number of events 7 • Baseline through end of study (Up to 15 weeks). All randomized participants.	17.9% 5/28 • Number of events 7 • Baseline through end of study (Up to 15 weeks). All randomized participants.
General disorders Fatigue	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.4% 1/29 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.
General disorders Injection site reaction	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	6.9% 2/29 • Number of events 3 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Infections and infestations Pharyngitis	7.7% 2/26 • Number of events 3 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/29 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Infections and infestations Upper respiratory tract infection	7.7% 2/26 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	6.9% 2/29 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Infections and infestations Urinary tract infection	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/29 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	13.8% 4/29 • Number of events 4 • Baseline through end of study (Up to 15 weeks). All randomized participants.	21.4% 6/28 • Number of events 7 • Baseline through end of study (Up to 15 weeks). All randomized participants.	28.6% 8/28 • Number of events 20 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Musculoskeletal and connective tissue disorders Back pain	7.7% 2/26 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.4% 1/29 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.6% 1/28 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Musculoskeletal and connective tissue disorders Muscle spasms	3.8% 1/26 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.4% 1/29 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/29 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Nervous system disorders Dizziness	7.7% 2/26 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/29 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.6% 1/28 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	10.7% 3/28 • Number of events 9 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Nervous system disorders Headache	7.7% 2/26 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	6.9% 2/29 • Number of events 5 • Baseline through end of study (Up to 15 weeks). All randomized participants.	21.4% 6/28 • Number of events 10 • Baseline through end of study (Up to 15 weeks). All randomized participants.	17.9% 5/28 • Number of events 27 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Respiratory, thoracic and mediastinal disorders Cough	3.8% 1/26 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	6.9% 2/29 • Number of events 3 • Baseline through end of study (Up to 15 weeks). All randomized participants.	7.1% 2/28 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	0.00% 0/28 • Baseline through end of study (Up to 15 weeks). All randomized participants.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/26 • Baseline through end of study (Up to 15 weeks). All randomized participants.	6.9% 2/29 • Number of events 2 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.6% 1/28 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.	3.6% 1/28 • Number of events 1 • Baseline through end of study (Up to 15 weeks). All randomized participants.