Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Chronic Migraine Prevention (NCT NCT02066415)

NCT ID: NCT02066415

Last Updated: 2022-10-12

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

667 participants

Primary outcome timeframe

4-week baseline phase and the last 4 weeks of the 12-week treatment phase

Results posted on

2022-10-12

Participant Flow

This study was conducted at 69 centers in Canada, Czech Republic, Denmark, Germany, Finland, Norway, Poland, Sweden, United Kingdom, and the United States of America (USA). The first participant was enrolled on 05 March 2014 and the last participant enrolled on 05 November 2015.

Participants were randomized in a 3:2:2 ratio to receive placebo, erenumab 70 mg, or erenumab 140 mg. Randomization was stratified by region (North America vs Other) and medication overuse status at baseline (Yes vs No).

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Overall Study STARTED	286	191	190
Overall Study Received Study Drug	282	190	188
Overall Study COMPLETED	265	184	182
Overall Study NOT COMPLETED	21	7	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Overall Study Decision by Sponsor	5	4	2
Overall Study Withdrawal by Subject	9	1	4
Overall Study Lost to Follow-up	7	2	2

Baseline Characteristics

Participants with available data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=286 Participants Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg n=191 Participants Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg n=190 Participants Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Total n=667 Participants Total of all reporting groups
Age, Continuous	42.1 years STANDARD_DEVIATION 11.3 • n=286 Participants	41.4 years STANDARD_DEVIATION 11.3 • n=191 Participants	42.9 years STANDARD_DEVIATION 11.1 • n=190 Participants	42.1 years STANDARD_DEVIATION 11.3 • n=667 Participants
Age, Customized 18 to 64 years	285 Participants n=286 Participants	191 Participants n=191 Participants	190 Participants n=190 Participants	666 Participants n=667 Participants
Age, Customized 65 to 74 years	1 Participants n=286 Participants	0 Participants n=191 Participants	0 Participants n=190 Participants	1 Participants n=667 Participants
Sex: Female, Male Female	226 Participants n=286 Participants	166 Participants n=191 Participants	160 Participants n=190 Participants	552 Participants n=667 Participants
Sex: Female, Male Male	60 Participants n=286 Participants	25 Participants n=191 Participants	30 Participants n=190 Participants	115 Participants n=667 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=286 Participants	7 Participants n=191 Participants	10 Participants n=190 Participants	26 Participants n=667 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	277 Participants n=286 Participants	184 Participants n=191 Participants	180 Participants n=190 Participants	641 Participants n=667 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=286 Participants	0 Participants n=191 Participants	0 Participants n=190 Participants	0 Participants n=667 Participants
Race/Ethnicity, Customized Asian	4 Participants n=286 Participants	4 Participants n=191 Participants	0 Participants n=190 Participants	8 Participants n=667 Participants
Race/Ethnicity, Customized Black or African American	11 Participants n=286 Participants	10 Participants n=191 Participants	6 Participants n=190 Participants	27 Participants n=667 Participants
Race/Ethnicity, Customized White	268 Participants n=286 Participants	176 Participants n=191 Participants	184 Participants n=190 Participants	628 Participants n=667 Participants
Race/Ethnicity, Customized Other	3 Participants n=286 Participants	1 Participants n=191 Participants	0 Participants n=190 Participants	4 Participants n=667 Participants
Prior Migraine Prophylactic Medication Yes	218 Participants n=286 Participants	138 Participants n=191 Participants	136 Participants n=190 Participants	492 Participants n=667 Participants
Prior Migraine Prophylactic Medication No	68 Participants n=286 Participants	53 Participants n=191 Participants	54 Participants n=190 Participants	175 Participants n=667 Participants
Prior Migraine Prophylactic Treatment Failure Yes	200 Participants n=286 Participants	127 Participants n=191 Participants	126 Participants n=190 Participants	453 Participants n=667 Participants
Prior Migraine Prophylactic Treatment Failure No	86 Participants n=286 Participants	64 Participants n=191 Participants	64 Participants n=190 Participants	214 Participants n=667 Participants
Region North America	135 Participants n=286 Participants	91 Participants n=191 Participants	89 Participants n=190 Participants	315 Participants n=667 Participants
Region Other	151 Participants n=286 Participants	100 Participants n=191 Participants	101 Participants n=190 Participants	352 Participants n=667 Participants
Medication Overuse Status Yes	117 Participants n=286 Participants	79 Participants n=191 Participants	78 Participants n=190 Participants	274 Participants n=667 Participants
Medication Overuse Status No	169 Participants n=286 Participants	112 Participants n=191 Participants	112 Participants n=190 Participants	393 Participants n=667 Participants
Monthly Migraine Days	18.22 days STANDARD_DEVIATION 4.73 • n=286 Participants	17.85 days STANDARD_DEVIATION 4.39 • n=191 Participants	17.78 days STANDARD_DEVIATION 4.72 • n=190 Participants	17.99 days STANDARD_DEVIATION 4.63 • n=667 Participants
Disease Duration of Migraine With or Without Aura	22.21 years STANDARD_DEVIATION 12.63 • n=285 Participants • Participants with available data	20.71 years STANDARD_DEVIATION 12.83 • n=191 Participants • Participants with available data	21.92 years STANDARD_DEVIATION 11.80 • n=189 Participants • Participants with available data	21.70 years STANDARD_DEVIATION 12.46 • n=665 Participants • Participants with available data

PRIMARY outcome

Timeframe: 4-week baseline phase and the last 4 weeks of the 12-week treatment phase

Population: The efficacy analysis set included participants who received at least 1 dose of study drug and completed at least 1 post-baseline monthly eDiary measurement. The number of participants analyzed includes those with observed data at week 12.

Outcome measures

Outcome measures
Measure	Placebo n=267 Participants Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg n=178 Participants Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg n=182 Participants Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Change From Baseline in Monthly Migraine Days	-4.18 migraine days / month Interval -4.86 to -3.5	-6.64 migraine days / month Interval -7.47 to -5.81	-6.63 migraine days / month Interval -7.45 to -5.8

SECONDARY outcome

Timeframe: 4-week baseline phase and the last 4 weeks of the 12-week treatment phase

Population: The efficacy analysis set included participants who received at least 1 dose of study drug and completed at least 1 post-baseline monthly eDiary measurement. Participants with missing post-baseline data were counted as non-responders.

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine without aura or a migraine with aura. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase and during the last 4 weeks of treatment. At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 4 weeks of the 12-week treatment phase \* 100 / baseline monthly migraine days was less than or equal to -50%.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg n=188 Participants Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg n=187 Participants Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Baseline	23.5 percentage of participants	39.9 percentage of participants	41.2 percentage of participants

SECONDARY outcome

Timeframe: 4-week baseline phase and the last 4 weeks of the 12-week treatment phase

Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications.

Outcome measures

Outcome measures
Measure	Placebo n=267 Participants Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg n=178 Participants Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg n=182 Participants Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days	-1.58 acute migraine treatment days / month Interval -2.05 to -1.11	-3.45 acute migraine treatment days / month Interval -4.02 to -2.87	-4.13 acute migraine treatment days / month Interval -4.7 to -3.56

SECONDARY outcome

Timeframe: 4-week baseline phase and the last 4 weeks of the 12-week treatment phase

The cumulative duration of any qualified headache between monthly doses of study drug regardless of acute treatment use. A qualified headache was defined as follows: * a qualified migraine headache (including an aura-only event that is treated with acute migraine-specific medication), or * a qualified non-migraine headache, which is a headache that lasted continuously for ≥ 4 hours and was not a qualified migraine headache, or * a headache of any duration for which acute headache treatment was administered.

Outcome measures

Outcome measures
Measure	Placebo n=267 Participants Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg n=178 Participants Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg n=182 Participants Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Change From Baseline in Cumulative Monthly Headache Hours	-55.22 hours / month Interval -66.38 to -44.06	-64.76 hours / month Interval -78.34 to -51.17	-74.53 hours / month Interval -88.05 to -61.01

SECONDARY outcome

Timeframe: From the first dose of study drug up to 16 weeks after the last dose (24 weeks)

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

Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4, where: Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 = Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death related to AE.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg n=190 Participants Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg n=188 Participants Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Number of Participants With Adverse Events Any adverse event	110 Participants	83 Participants	88 Participants
Number of Participants With Adverse Events AEs grade ≥ 2	65 Participants	45 Participants	42 Participants
Number of Participants With Adverse Events AEs grade ≥ 3	13 Participants	11 Participants	4 Participants
Number of Participants With Adverse Events AEs grade ≥ 4	0 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events Serious adverse events	7 Participants	6 Participants	2 Participants
Number of Participants With Adverse Events AEs leading to discontinuation of study drug	2 Participants	0 Participants	2 Participants
Number of Participants With Adverse Events Fatal adverse events	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and weeks 2, 4, 8, 12 and 24

Population: Randomized participants who received at least one dose of study drug and with available post-baseline antibody data. This endpoint was analyzed in the erenumab treatment groups only.

Blood samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against erenumab. Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based bioassay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay). Developing antibody incidence indicates participants with a negative or no result at baseline and a positive result at any time post-baseline. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies.

Outcome measures

Outcome measures
Measure	Placebo Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg n=189 Participants Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg n=187 Participants Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Number of Participants Who Developed Antibodies to Erenumab Binding antibody positive	—	11 Participants	3 Participants
Number of Participants Who Developed Antibodies to Erenumab Neutralizing antibody positive	—	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 16 other events

Deaths: 0 deaths

Erenumab 70 mg

Serious events: 6 serious events

Other events: 6 other events

Deaths: 0 deaths

Erenumab 140 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=282 participants at risk Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg n=190 participants at risk Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg n=188 participants at risk Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Infections and infestations Nasopharyngitis	5.7% 16/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.2% 6/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.6% 3/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

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	Placebo n=282 participants at risk Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 70 mg n=190 participants at risk Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.	Erenumab 140 mg n=188 participants at risk Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Gastrointestinal disorders Abdominal adhesions	0.00% 0/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	0.00% 0/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Pancreatitis	0.35% 1/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	0.35% 1/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Non-cardiac chest pain	0.00% 0/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Hepatobiliary disorders Cholecystitis	0.35% 1/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Appendicitis	0.00% 0/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Parotitis	0.35% 1/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	0.35% 1/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Cartilage injury	0.00% 0/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.35% 1/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroma	0.00% 0/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Migraine	0.35% 1/282 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/190 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From the first dose of study drug up to 16 weeks after the last dose (a total of 24 weeks) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.