Trial Outcomes & Findings for Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg, Ezetimibe 10mg, and Atorvastatin 20 mg Triplet Therapy in Patients With Elevated LDL-C (NCT NCT03051100)

Last Updated: 2020-04-03

Results Overview

Percent change from Baseline is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Percent change from Baseline in LDL-C was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing LDL-C values were imputed using last observation carried forward (LOCF), with only post-Baseline values carried forward. If LDL-C was measured (i.e., if TG was \>400 mg/dL or LDL-C was \<50 mg/dL), the measured values were used in the analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

Baseline; Week 6

Results posted on

2020-04-03

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received matching oral placebo once a day.	Triplet Therapy Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day.
Overall Study STARTED	20	43
Overall Study COMPLETED	19	43
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching oral placebo once a day.	Triplet Therapy Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day.
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg, Ezetimibe 10mg, and Atorvastatin 20 mg Triplet Therapy in Patients With Elevated LDL-C

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=20 Participants Participants received matching oral placebo once a day.	Triplet Therapy n=43 Participants Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day.	Total n=63 Participants Total of all reporting groups
Age, Continuous	61.2 years STANDARD_DEVIATION 7.77 • n=5 Participants	61.2 years STANDARD_DEVIATION 12.26 • n=7 Participants	61.2 years STANDARD_DEVIATION 10.97 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	26 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	17 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized White	16 Participants n=5 Participants	34 Participants n=7 Participants	50 Participants n=5 Participants
Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values LDL-C	155.90 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 13.749 • n=5 Participants	154.29 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 17.913 • n=7 Participants	154.80 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 16.609 • n=5 Participants
Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values non-HDL-C	183.13 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 18.363 • n=5 Participants	183.59 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 27.347 • n=7 Participants	183.44 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 24.698 • n=5 Participants
Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values HDL-C	52.03 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 12.977 • n=5 Participants	52.05 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 12.936 • n=7 Participants	52.04 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 12.844 • n=5 Participants
Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values TC	235.13 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 21.196 • n=5 Participants	235.67 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 26.992 • n=7 Participants	235.50 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 25.125 • n=5 Participants
Baseline LDL-C, non-HDL-C, HDL-C, TC, and TG Values TG	139.53 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 62.475 • n=5 Participants	150.70 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 81.375 • n=7 Participants	147.15 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 75.560 • n=5 Participants
Baseline Apolipoprotein B (apoB) Values	119.2 mg/dL STANDARD_DEVIATION 15.25 • n=5 Participants	118.0 mg/dL STANDARD_DEVIATION 19.89 • n=7 Participants	118.4 mg/dL STANDARD_DEVIATION 18.42 • n=5 Participants
Baseline High-Sensitivity C-Reactive Protein (hs-CRP) Values	1.64 milligrams per Liter n=5 Participants	1.94 milligrams per Liter n=7 Participants	1.88 milligrams per Liter n=5 Participants

PRIMARY outcome

Timeframe: Baseline; Week 6

Population: Modified Intent-to-Treat Population: all randomized participants who received at least 1 dose of investigational medicinal product (IMP) and who had a Baseline assessment and at least 1 post-Baseline assessment, excluding any assessment taken more than 2 days after a dose of IMP. Only those participants with data available were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received matching oral placebo once a day.	Triplet Therapy n=43 Participants Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 6	-3.1 percent change Standard Error 3.27	-63.6 percent change Standard Error 1.67

SECONDARY outcome

Timeframe: Baseline; Week 6

Population: Modified Intent-to-Treat Population. Only those participants with data available were analyzed.

Percent change from Baseline is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Baseline apolipoprotein B (apoB) was measured only at predose/Day 1. Percent change from Baseline was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing values were imputed using LOCF, with only post-Baseline values carried forward. non-HDL-C, non-high-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received matching oral placebo once a day.	Triplet Therapy n=43 Participants Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day.
Percent Change From Baseline in Lipid Profile Parameters at Week 6 non-HDL-C	-1.3 percent change Standard Error 2.56	-60.0 percent change Standard Error 1.60
Percent Change From Baseline in Lipid Profile Parameters at Week 6 TC	-1.1 percent change Standard Error 2.24	-47.1 percent change Standard Error 1.63
Percent Change From Baseline in Lipid Profile Parameters at Week 6 apoB	0.6 percent change Standard Error 2.24	-53.5 percent change Standard Error 1.57
Percent Change From Baseline in Lipid Profile Parameters at Week 6 TG	8.9 percent change Standard Error 5.95	-27.4 percent change Standard Error 2.79
Percent Change From Baseline in Lipid Profile Parameters at Week 6 HDL-C	0.4 percent change Standard Error 2.26	-1.1 percent change Standard Error 1.47

SECONDARY outcome

Timeframe: Baseline; Week 6

Population: Modified Intent-to-Treat Population. Only those participants with data available were analyzed.

Percent change is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the predose Day 1/Week 0 (Treatment Visit 1) value. If only one value is available either at Week -1 (Screening Visit 2) or Week 0 (Treatment Visit 1), then that value is used as Baseline. Missing values were imputed using LOCF, with only post-Baseline values carried forward.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received matching oral placebo once a day.	Triplet Therapy n=41 Participants Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day.
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 6	-2.7 percent change Interval -19.8 to 17.9	-47.7 percent change Interval -66.0 to -22.7

SECONDARY outcome

Timeframe: Week 6

Population: Modified Intent-to-Treat Population. Only those participants with data available were analyzed.

Analysis was based on LOCF values. If LDL-C was measured (i.e., if TG was \>400 mg/dL or LDL-C was \<50 mg/dL), the measured values were used in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received matching oral placebo once a day.	Triplet Therapy n=41 Participants Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day.
Number of Participants With LDL-C <70 mg/dL at Week 6	0 Participants	37 Participants

SECONDARY outcome

Timeframe: Baseline; Week 6

Population: Modified Intent-to-Treat Population. Only those participants with data available were analyzed.

If LDL-C was measured (i.e., if TG was \>400 mg/dL or LDL-C was \<50 mg/dL), the measured values were used in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received matching oral placebo once a day.	Triplet Therapy n=41 Participants Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day.
Number of Participants With LDL-C Reduction ≥50% From Baseline at Week 6	0 Participants	39 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Triplet Therapy

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Director

Esperion Therapeutics, Inc.

Phone: 1-833-377-7633

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If the Principal Investigator plans to publish information from the study, a copy of the manuscript should be provided to the Sponsor for review before submission for publication or presentation. The Sponsor may request that that publication be withheld.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=20 participants at risk Participants received matching oral placebo once a day.	Triplet Therapy n=43 participants at risk Participants received bempedoic acid 180 milligrams (mg), ezetimibe 10 mg, and atorvastatin 20 mg orally once a day.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	4.7% 2/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	4.7% 2/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Musculoskeletal and connective tissue disorders Arthralgia	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Musculoskeletal and connective tissue disorders Back pain	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Musculoskeletal and connective tissue disorders Muscle spasms	10.0% 2/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Musculoskeletal and connective tissue disorders Joint swelling	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	0.00% 0/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	0.00% 0/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Investigations Hepatic enzyme increased	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	4.7% 2/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Investigations Liver function test increased	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Investigations Platelet count increased	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Nervous system disorders Headache	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	4.7% 2/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Nervous system disorders Dizziness	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Nervous system disorders Dizziness postural	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Nervous system disorders Tension headache	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Infections and infestations Gastroenteritis	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Infections and infestations Rhinitis	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Infections and infestations Sinusitis	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Infections and infestations Folliculitis	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	0.00% 0/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Gastrointestinal disorders Diarrhoea	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	4.7% 2/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Gastrointestinal disorders Abdominal pain	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Gastrointestinal disorders Constipation	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Gastrointestinal disorders Dyspepsia	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Gastrointestinal disorders Nausea	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Skin and subcutaneous tissue disorders Rash	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	4.7% 2/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
General disorders Fatigue	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	4.7% 2/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Blood and lymphatic system disorders Anaemia	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Ear and labyrinth disorders Ear pain	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	0.00% 0/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Injury, poisoning and procedural complications Laceration	0.00% 0/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	2.3% 1/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Injury, poisoning and procedural complications Arthropod bite	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	0.00% 0/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Injury, poisoning and procedural complications Fall	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	0.00% 0/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	0.00% 0/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.
Psychiatric disorders Depression	5.0% 1/20 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.	0.00% 0/43 • up to 6 weeks plus 30 days Treatment-emergent adverse events, defined as those events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after last dose of IMP, are reported.