Trial Outcomes & Findings for A Study to Compare the Effect of a Double Dose of Two Long-acting Insulin Therapies in Participants With Type 2 Diabetes (NCT NCT02132637)

Last Updated: 2019-09-18

Results Overview

The percentage was calculated by dividing the number of participants with clinically significant hypoglycemia events defined as blood glucose \<54 milligrams per deciliter (mg/dL) (3.0 millimole per liter \[mmol/L\]) or symptoms of severe hypoglycemia by the total number of participants analyzed, multiplied by 100.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

68 participants

Primary outcome timeframe

Predose to 84 Hours Post Double Dose

Results posted on

2019-09-18

Participant Flow

Participant milestones

Participant milestones
Measure	Insulin Peglispro/Insulin Glargine Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in the first study period. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay. Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in the second study period. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine/Insulin Peglispro Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in the first study period. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay. Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in the second study period. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.
Study Period 1 STARTED	34	34
Study Period 1 Received at Least One Dose of Study Drug	34	34
Study Period 1 COMPLETED	33	30
Study Period 1 NOT COMPLETED	1	4
Study Period 2 (Crossover) STARTED	33	30
Study Period 2 (Crossover) COMPLETED	31	29
Study Period 2 (Crossover) NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Peglispro/Insulin Glargine Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in the first study period. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay. Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in the second study period. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine/Insulin Peglispro Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in the first study period. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay. Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in the second study period. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.
Study Period 1 Withdrawal by Subject	0	4
Study Period 1 Physician Decision	1	0
Study Period 2 (Crossover) Adverse Event	0	1
Study Period 2 (Crossover) Physician Decision	2	0

Baseline Characteristics

A Study to Compare the Effect of a Double Dose of Two Long-acting Insulin Therapies in Participants With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Peglispro/Insulin Glargine n=34 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in the first study period. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay. Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in the second study period. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine/Insulin Peglispro n=34 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in the first study period. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay. Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in the second study period. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Total n=68 Participants Total of all reporting groups
Age, Continuous	57.82 years STANDARD_DEVIATION 8.06 • n=5 Participants	57.74 years STANDARD_DEVIATION 5.86 • n=7 Participants	57.78 years STANDARD_DEVIATION 6.99 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=5 Participants	29 Participants n=7 Participants	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants	34 Participants n=7 Participants	66 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Germany	29 Participants n=5 Participants	29 Participants n=7 Participants	58 Participants n=5 Participants

PRIMARY outcome

Timeframe: Predose to 84 Hours Post Double Dose

Population: All randomized participants who received the double dose of study drug and had evaluable hypoglycemia data were included in the analysis.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=61 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=62 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Percentage of Participants With Clinically Significant Hypoglycemia	6.6 percentage of participants	35.5 percentage of participants

SECONDARY outcome

Timeframe: Predose to 12 Hours Post Double Dose

Population: All randomized participants who received the double dose of study drug and had evaluable hypoglycemia data were included in the analysis.

The percentage was calculated by dividing the number of participants with clinically significant hypoglycemia events defined as blood glucose \<54 mg/dL (3.0 mmol/L) or symptoms of severe hypoglycemia by the total number of participants analyzed, multiplied by 100.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=61 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=62 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Percentage of Participants With Clinically Significant Hypoglycemia 12 Hours Post Double Dose	1.6 percentage of participants	22.6 percentage of participants

SECONDARY outcome

Timeframe: Predose to 12 Hours Post Double Dose and 84 Hours Post Double Dose

Population: All randomized participants who received the double dose of study drug and had evaluable hypoglycemia data were included in the analysis.

The percentage was calculated by dividing the number of participants with hypoglycemia events defined as blood glucose ≤70 mg/dL (3.9 mmol/L) by the total number of participants analyzed, multiplied by 100.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=61 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=62 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Percentage of Participants With Hypoglycemia 12 Hours Post Double Dose	19.7 percentage of participants	64.5 percentage of participants
Percentage of Participants With Hypoglycemia 84 Hours Post Double Dose	42.6 percentage of participants	82.3 percentage of participants

SECONDARY outcome

Timeframe: Predose to 84 Hours Post Double Dose

Population: All randomized participants who received the double dose of study drug and had blood glucose ≤70 mg/dL (3.9 mmol/L) during the first 84 hours after the double dose were included in the analysis.

Nadir glucose was defined as the lowest blood glucose for a participant with blood glucose ≤70 mg/dL (3.9 mmol/L). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=26 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=51 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Nadir Glucose	61.70 mg/dL Standard Error 1.36	55.93 mg/dL Standard Error 0.97

SECONDARY outcome

Timeframe: Predose to 84 Hours Post Double Dose

Nadir glucose was defined as the lowest blood glucose for a participant with blood glucose ≤70 mg/dL (3.9 mmol/L). The average time was calculated by dividing the sum of time from double dose to the nadir glucose for participants with blood glucose ≤70 mg/dL (3.9 mmol/L) by the number of participants with blood glucose ≤70 mg/dL (3.9 mmol/L) during the first 84 hours after the double dose.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=26 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=51 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Time to the Nadir Glucose	35.92 hours Standard Deviation 26.37	28.15 hours Standard Deviation 23.46

SECONDARY outcome

Timeframe: Predose to 84 Hours Post Double Dose

Population: All randomized participants who received the double dose of study drug and had evaluable hypoglycemia data were included in the analysis.

The duration in minutes of each hypoglycemia episode with glucose ≤70 mg/dL (3.9 mmol/L) was calculated from start time to end time. The duration for a participant was the sum of the durations over the multiple hypoglycemia episodes. LS means were calculated using an MMRM analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=61 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=62 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Duration of Glucose ≤70 mg/dL	95.28 Minutes per participant Standard Error 37.57	362.26 Minutes per participant Standard Error 37.26

SECONDARY outcome

Timeframe: Day 1, Day 2, and Day 3 Following Double Dose

Population: All randomized participants who received the double dose of study drug and had evaluable fasting blood glucose data were included in the analysis.

Fasting blood glucose (FBG) was measured by self-monitored blood glucose. LS means were calculated by MMRM analysis with fixed effects of treatment, dosing day, sequence, period, interaction of treatment and dosing day, baseline basal insulin dose stratification factor, and baseline FBG.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=62 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=62 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Fasting Blood Glucose Day 3	102.18 mg/dL Standard Error 2.99	86.27 mg/dL Standard Error 3.00
Fasting Blood Glucose Day 1	102.03 mg/dL Standard Error 2.90	85.61 mg/dL Standard Error 2.87
Fasting Blood Glucose Day 2	100.94 mg/dL Standard Error 2.92	86.16 mg/dL Standard Error 2.91

SECONDARY outcome

Timeframe: Preprandial to 3 Hours Postprandial during the day following the standard dose

Population: All randomized participants who received at least one dose of study drug and had evaluable glucose data were included in the analysis.

Glucose AUC within 3 hours after each meal assessed by the AUC of glucose from preprandial to 3 hours postprandial. LS means were calculated using an MMRM analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=62 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=63 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC) Breakfast	633.50 mg/dL*h Standard Error 15.59	568.64 mg/dL*h Standard Error 15.51
Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC) Lunch	566.00 mg/dL*h Standard Error 19.92	568.20 mg/dL*h Standard Error 19.84
Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC) Dinner	564.68 mg/dL*h Standard Error 15.95	577.46 mg/dL*h Standard Error 15.95

SECONDARY outcome

Timeframe: Preprandial to 3 Hours Postprandial during the day following the standard dose

Population: All randomized participants who received at least one dose of study drug and had evaluable glucose data were included in the analysis.

Glucose AUC excursion within 3 hours after each meal assessed by the AUC of adjusted glucose (= observed glucose - preprandial glucose) from preprandial to 3 hours postprandial. LS means were calculated using an MMRM analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=62 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=63 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC) Excursion Breakfast	266.33 mg/dL*h Standard Error 12.04	270.32 mg/dL*h Standard Error 11.98
Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC) Excursion Lunch	-2.38 mg/dL*h Standard Error 11.42	36.92 mg/dL*h Standard Error 11.34
Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC) Excursion Dinner	134.40 mg/dL*h Standard Error 10.20	150.23 mg/dL*h Standard Error 10.20

SECONDARY outcome

Timeframe: 0-30 minutes during the meal tolerance test on the day following the standard dose

Population: All randomized participants who received at least one dose of study drug and had evaluable ΔC-peptide data were included in the analysis.

Beta cell function assessed by the change between pre meal tolerance test and 30 minutes post meal tolerance test in C-peptide corrected insulin/Glucose (ΔC-peptide corrected insulin/ΔGlucose). LS means were calculated using an MMRM analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.

Outcome measures

Outcome measures
Measure	Insulin Peglispro n=64 Participants Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=67 Participants Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Beta Cell Function	88.65 mmol/L Standard Error 8.43	103.62 mmol/L Standard Error 8.32

Adverse Events

Insulin Peglispro

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

Insulin Glargine

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Insulin Peglispro n=64 participants at risk Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=67 participants at risk Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Gastrointestinal disorders Gastritis erosive	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
Infections and infestations Otitis media	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Insulin Peglispro n=64 participants at risk Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.	Insulin Glargine n=67 participants at risk Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Blood and lymphatic system disorders Anaemia	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Cardiac disorders Tachycardia	1.6% 1/64 • Number of events 2 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Deafness unilateral	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Vertigo	3.1% 2/64 • Number of events 2 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	4.7% 3/64 • Number of events 3 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	3.0% 2/67 • Number of events 2 All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	4.7% 3/64 • Number of events 4 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	3.1% 2/64 • Number of events 2 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
General disorders Asthenia	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
General disorders Fatigue	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
General disorders Infusion site extravasation	0.00% 0/64 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
General disorders Peripheral swelling	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Infections and infestations Cellulitis	0.00% 0/64 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Eye disorders Conjunctivitis	0.00% 0/64 All participants who received at least 1 dose of study drug.	3.0% 2/67 • Number of events 2 All participants who received at least 1 dose of study drug.
Infections and infestations Cystitis	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	7.8% 5/64 • Number of events 5 All participants who received at least 1 dose of study drug.	9.0% 6/67 • Number of events 6 All participants who received at least 1 dose of study drug.
Infections and infestations Oral herpes	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Infections and infestations Paronychia	0.00% 0/64 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Infections and infestations Rhinitis	0.00% 0/64 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Ligament sprain	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Decreased appetite	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/64 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthritis	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	6.2% 4/64 • Number of events 5 All participants who received at least 1 dose of study drug.	6.0% 4/67 • Number of events 4 All participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Joint swelling	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	4.7% 3/64 • Number of events 3 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
Nervous system disorders Headache	17.2% 11/64 • Number of events 16 All participants who received at least 1 dose of study drug.	10.4% 7/67 • Number of events 7 All participants who received at least 1 dose of study drug.
General disorders Irritability	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Renal and urinary disorders Bladder pain	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
Renal and urinary disorders Pollakiuria	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	0.00% 0/67 All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/64 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.6% 1/64 • Number of events 1 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Ecchymosis	3.1% 2/64 • Number of events 3 All participants who received at least 1 dose of study drug.	4.5% 3/67 • Number of events 5 All participants who received at least 1 dose of study drug.
Vascular disorders Phlebitis	0.00% 0/64 All participants who received at least 1 dose of study drug.	1.5% 1/67 • Number of events 1 All participants who received at least 1 dose of study drug.