Trial Outcomes & Findings for Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities (NCT NCT01588496)

NCT ID: NCT01588496

Last Updated: 2018-11-29

Results Overview

LDL-C was quantified using the ultracentrifugation method.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

58 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2018-11-29

Participant Flow

Male and female adults and adolescents ages ≥ 12 to ≤ 65 years (≥ 12 to ≤ 80 years in Part B) with a diagnosis of homozygous familial hypercholesterolemia (HoFH) were eligible for this study. The first participant enrolled on 05 April 2012 and the last participant enrolled on 08 November 2013.

Part A was an open-label, single-arm, multicenter pilot study. Part B was a double-blind, randomized, placebo-controlled, multicenter study with expanded enrollment. In Part B participants were randomized in a 1:2 allocation stratified on the basis of screening low-density lipoprotein cholesterol (LDL-C) (\< 420 mg/dL vs ≥ 420 mg/dL).

Participant milestones

Participant milestones
Measure	Part A: Evolocumab Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Placebo Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Overall Study STARTED	8	17	33
Overall Study Received Treatment	8	16	33
Overall Study COMPLETED	8	16	33
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Evolocumab Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Placebo Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Overall Study Withdrawal by Subject	0	1	0

Baseline Characteristics

Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Evolocumab n=8 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Placebo n=17 Participants Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Part B: Evolocumab n=33 Participants Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.	Total n=58 Participants Total of all reporting groups
Age, Continuous	34.3 years STANDARD_DEVIATION 12.4 • n=99 Participants	32.8 years STANDARD_DEVIATION 13.7 • n=107 Participants	30.3 years STANDARD_DEVIATION 12.4 • n=206 Participants	31.6 years STANDARD_DEVIATION 12.7 • n=7 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	8 Participants n=107 Participants	16 Participants n=206 Participants	26 Participants n=7 Participants
Sex: Female, Male Male	6 Participants n=99 Participants	9 Participants n=107 Participants	17 Participants n=206 Participants	32 Participants n=7 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants	0 participants n=7 Participants
Race/Ethnicity, Customized Asian	0 participants n=99 Participants	1 participants n=107 Participants	1 participants n=206 Participants	2 participants n=7 Participants
Race/Ethnicity, Customized Black or African American	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants	0 participants n=7 Participants
Race/Ethnicity, Customized 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
Race/Ethnicity, Customized White	8 participants n=99 Participants	16 participants n=107 Participants	29 participants n=206 Participants	53 participants n=7 Participants
Race/Ethnicity, Customized Other	0 participants n=99 Participants	0 participants n=107 Participants	3 participants n=206 Participants	3 participants n=7 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants	1 participants n=7 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	8 participants n=99 Participants	17 participants n=107 Participants	32 participants n=206 Participants	57 participants n=7 Participants
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level < 420 mg/dL	0 participants n=99 Participants	11 participants n=107 Participants	21 participants n=206 Participants	32 participants n=7 Participants
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level ≥ 420 mg/dL	0 participants n=99 Participants	6 participants n=107 Participants	12 participants n=206 Participants	18 participants n=7 Participants
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level Missing	8 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants	8 participants n=7 Participants
LDL-C Concentration Part A	441.7 mg/dL STANDARD_DEVIATION 113.3 • n=99 Participants	NA mg/dL STANDARD_DEVIATION NA • n=107 Participants	NA mg/dL STANDARD_DEVIATION NA • n=206 Participants	441.7 mg/dL STANDARD_DEVIATION 113.3 • n=7 Participants
LDL-C Concentration Part B	NA mg/dL STANDARD_DEVIATION NA • n=99 Participants	335.8 mg/dL STANDARD_DEVIATION 146.0 • n=107 Participants	356.0 mg/dL STANDARD_DEVIATION 134.5 • n=206 Participants	349.4 mg/dL STANDARD_DEVIATION 137.2 • n=7 Participants
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration Part A	470.6 mg/dL STANDARD_DEVIATION 117.8 • n=99 Participants	NA mg/dL STANDARD_DEVIATION NA • n=107 Participants	NA mg/dL STANDARD_DEVIATION NA • n=206 Participants	470.6 mg/dL STANDARD_DEVIATION 117.8 • n=7 Participants
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration Part B	NA mg/dL STANDARD_DEVIATION NA • n=99 Participants	358.9 mg/dL STANDARD_DEVIATION 149.1 • n=107 Participants	374.9 mg/dL STANDARD_DEVIATION 136.9 • n=206 Participants	369.7 mg/dL STANDARD_DEVIATION 139.6 • n=7 Participants
Apolipoprotein B Concentration Part A	269.1 mg/dL STANDARD_DEVIATION 53.0 • n=99 Participants	NA mg/dL STANDARD_DEVIATION NA • n=107 Participants	NA mg/dL STANDARD_DEVIATION NA • n=206 Participants	269.1 mg/dL STANDARD_DEVIATION 53.0 • n=7 Participants
Apolipoprotein B Concentration Part B	NA mg/dL STANDARD_DEVIATION NA • n=99 Participants	208.6 mg/dL STANDARD_DEVIATION 79.5 • n=107 Participants	208.3 mg/dL STANDARD_DEVIATION 68.4 • n=206 Participants	208.4 mg/dL STANDARD_DEVIATION 71.4 • n=7 Participants
Total Cholesterol/HDL-C Ratio Part A	15.988 ratio STANDARD_DEVIATION 5.107 • n=99 Participants	NA ratio STANDARD_DEVIATION NA • n=107 Participants	NA ratio STANDARD_DEVIATION NA • n=206 Participants	15.988 ratio STANDARD_DEVIATION 5.107 • n=7 Participants
Total Cholesterol/HDL-C Ratio Part B	NA ratio STANDARD_DEVIATION NA • n=99 Participants	12.101 ratio STANDARD_DEVIATION 6.619 • n=107 Participants	11.972 ratio STANDARD_DEVIATION 6.387 • n=206 Participants	12.014 ratio STANDARD_DEVIATION 6.395 • n=7 Participants
Apolipoprotein B/Apolipoprotein A1 Ratio Part A	2.800 ratio STANDARD_DEVIATION 0.729 • n=99 Participants	NA ratio STANDARD_DEVIATION NA • n=107 Participants	NA ratio STANDARD_DEVIATION NA • n=206 Participants	2.800 ratio STANDARD_DEVIATION 0.729 • n=7 Participants
Apolipoprotein B/Apolipoprotein A1 Ratio Part B	NA ratio STANDARD_DEVIATION NA • n=99 Participants	2.053 ratio STANDARD_DEVIATION 0.967 • n=107 Participants	2.098 ratio STANDARD_DEVIATION 1.046 • n=206 Participants	2.084 ratio STANDARD_DEVIATION 1.011 • n=7 Participants
Lipoprotein(a) Concentration Part A	246.5 nmol/L n=99 Participants	NA nmol/L n=107 Participants	NA nmol/L n=206 Participants	246.5 nmol/L n=7 Participants
Lipoprotein(a) Concentration Part B	NA nmol/L n=99 Participants	127.5 nmol/L n=107 Participants	76.0 nmol/L n=206 Participants	100.5 nmol/L n=7 Participants
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration Part A	598.6 ng/mL STANDARD_DEVIATION 121.1 • n=99 Participants	NA ng/mL STANDARD_DEVIATION NA • n=107 Participants	NA ng/mL STANDARD_DEVIATION NA • n=206 Participants	598.6 ng/mL STANDARD_DEVIATION 121.1 • n=7 Participants
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration Part B	NA ng/mL STANDARD_DEVIATION NA • n=99 Participants	674.2 ng/mL STANDARD_DEVIATION 180.0 • n=107 Participants	640.3 ng/mL STANDARD_DEVIATION 207.5 • n=206 Participants	651.4 ng/mL STANDARD_DEVIATION 197.7 • n=7 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Part A full analysis set (all enrolled participants who received at least 1 dose of evolocumab)

LDL-C was quantified using the ultracentrifugation method.

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=8 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12	-16.5 percent change Standard Error 6.7	—

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Part B full analysis set (all enrolled participants who received at least 1 dose of investigational product)

LDL-C was quantified using the ultracentrifugation method.

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=16 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab n=33 Participants Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12	7.88 percent change Standard Error 5.26	-23.05 percent change Standard Error 3.78

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part A full analysis set

LDL-C was quantified using the ultracentrifugation method.

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=8 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part A: Change From Baseline in LDL-C at Week 12	-70.6 mg/dL Standard Error 32.3	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part A full analysis set

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=8 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12	-16.6 percent change Standard Error 6.5	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part A full analysis set

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=8 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part A: Percent Change From Baseline in Apolipoprotein B at Week 12	-14.9 percent change Standard Error 5.0	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part A full analysis set

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=8 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12	-18.319 percent change Standard Error 6.058	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part A full analysis set

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=8 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12	-15.65 percent change Standard Error 4.690	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part A full analysis set

LDL-C was quantified using the ultracentrifugation method.

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=8 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12	50.0 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part A full analysis set

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=8 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12	-151.3 ng/mL Standard Error 81.7	—

SECONDARY outcome

Timeframe: Baseline and Weeks 6 and 12

Population: Part B full analysis set

LDL-C was quantified using the ultracentrifugation method.

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=16 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab n=33 Participants Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12	4.22 percent change Standard Error 4.56	-25.56 percent change Standard Error 3.28

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part B full analysis set

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=16 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab n=33 Participants Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part B: Percent Change From Baseline in Apolipoprotein B at Week 12	3.97 percent change Standard Error 4.74	-19.17 percent change Standard Error 3.46

SECONDARY outcome

Timeframe: Baseline and Weeks 6 and 12

Population: Part B full analysis set

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=16 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab n=33 Participants Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12	2.65 percent change Standard Error 4.42	-20.24 percent change Standard Error 3.18

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part B full anlaysis set

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=16 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab n=33 Participants Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12	2.43 percent change Standard Error 5.49	-9.40 percent change Standard Error 4.07

SECONDARY outcome

Timeframe: Baseline and Weeks 6 and 12

Population: Part B full analysis set

Outcome measures

Outcome measures
Measure	Part A: Evolocumab n=16 Participants Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Part B: Evolocumab n=33 Participants Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12	-1.43 percent change Standard Error 4.78	-12.71 percent change Standard Error 3.53

Adverse Events

Part A: OL Evolocumab

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part B: DB Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Part B: DB Evolocumab

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Part A: OL Evolocumab n=8 participants at risk Participants received open-label (OL) evolocumab 420 mg subcutaneously once a month for 12 weeks.	Part B: DB Placebo n=16 participants at risk Participants received double-blind (DB) placebo subcutaneously once a month for 12 weeks.	Part B: DB Evolocumab n=33 participants at risk Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Cardiac disorders Palpitations	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Gastrointestinal disorders Abdominal pain	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	3.0% 1/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Gastrointestinal disorders Dyspepsia	12.5% 1/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Gastrointestinal disorders Nausea	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	12.5% 2/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
General disorders Chest pain	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	3.0% 1/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
General disorders Fatigue	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
General disorders Injection site pain	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
General disorders Medical device site reaction	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
General disorders Pain	12.5% 1/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Infections and infestations Bronchitis	12.5% 1/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Infections and infestations Gastroenteritis	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.1% 2/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Infections and infestations Influenza	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	9.1% 3/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Infections and infestations Nasopharyngitis	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.1% 2/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Infections and infestations Upper respiratory tract infection	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	9.1% 3/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Investigations Blood creatine phosphokinase increased	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Investigations Weight decreased	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Nervous system disorders Dizziness	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Nervous system disorders Headache	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Nervous system disorders Presyncope	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	6.2% 1/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	3.0% 1/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	12.5% 1/8 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/16 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.	0.00% 0/33 • 12 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.