Trial Outcomes & Findings for A Controlled Trial of Erenumab in Migraine Prevention (NCT NCT03812224)

Last Updated: 2024-02-21

Results Overview

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 with or without aura, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria: 1. ≥ 2 of the following pain features: * unilateral * throbbing * moderate to severe * exacerbated with exercise/physical activity 2. ≥ 1 of the following associated symptoms: * nausea * vomiting * photophobia and phonophobia The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period minus the number of migraine days during the 4-week baseline period.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

261 participants

Primary outcome timeframe

4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period

Results posted on

2024-02-21

Participant Flow

This study was conducted at 41 centers in Japan. The study consisted of a 24-week double-blind treatment period (DBTP), a 28-week open-label treatment period (OLTP), followed by an 8-week safety follow-up (12 weeks after the last dose of investigational product).

Eligible participants were randomized 1:1 to erenumab 70 mg or placebo. Randomization was stratified by migraine type (episodic migraine \[EM\] / chronic migraine \[CM\]) and migraine preventive treatment status (ever used \[prior and/or current\] or never used).

Participant milestones

Participant milestones
Measure	Placebo QM Participants randomized to receive placebo once a month (QM) for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.	Erenumab 70 mg QM Participants randomized to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.
Double-blind Treatment Period STARTED	131	130
Double-blind Treatment Period COMPLETED	127	127
Double-blind Treatment Period NOT COMPLETED	4	3
Open-label Treatment Period STARTED	127	127
Open-label Treatment Period COMPLETED	125	124
Open-label Treatment Period NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo QM Participants randomized to receive placebo once a month (QM) for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.	Erenumab 70 mg QM Participants randomized to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.
Double-blind Treatment Period Withdrawal by Subject	4	2
Double-blind Treatment Period Decision by Sponsor	0	1
Open-label Treatment Period Withdrawal by Subject	2	2
Open-label Treatment Period Decision by Sponsor	0	1

Baseline Characteristics

A Controlled Trial of Erenumab in Migraine Prevention

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo QM n=131 Participants Participants randomized to receive placebo once a month (QM) for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.	Erenumab 70 mg QM n=130 Participants Participants randomized to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.	Total n=261 Participants Total of all reporting groups
Age, Continuous	44.6 years STANDARD_DEVIATION 9.3 • n=5 Participants	44.2 years STANDARD_DEVIATION 8.5 • n=7 Participants	44.4 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	116 Participants n=5 Participants	111 Participants n=7 Participants	227 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	19 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	131 Participants n=5 Participants	130 Participants n=7 Participants	261 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	131 Participants n=5 Participants	130 Participants n=7 Participants	261 Participants n=5 Participants
Migraine Type Episodic migraine	80 Participants n=5 Participants	79 Participants n=7 Participants	159 Participants n=5 Participants
Migraine Type Chronic migraine	51 Participants n=5 Participants	51 Participants n=7 Participants	102 Participants n=5 Participants
Prior Migraine Preventive Treatment Status Ever used (including prior and/or current users)	100 Participants n=5 Participants	100 Participants n=7 Participants	200 Participants n=5 Participants
Prior Migraine Preventive Treatment Status Never used	31 Participants n=5 Participants	30 Participants n=7 Participants	61 Participants n=5 Participants
Monthly Migraine Days	11.84 days / month STANDARD_DEVIATION 5.70 • n=5 Participants	12.40 days / month STANDARD_DEVIATION 5.99 • n=7 Participants	12.12 days / month STANDARD_DEVIATION 5.84 • n=5 Participants

PRIMARY outcome

Timeframe: 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period

Population: The efficacy analysis set included randomized participants who received at least 1 dose of investigational product and had at least 1 change from baseline measurement in MMD during the DBTP. Observed data.

Outcome measures

Outcome measures
Measure	Placebo QM n=128 Participants Participants received placebo once a month for 24 weeks during the double-blind treatment period.	Erenumab 70 mg QM n=129 Participants Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period.
Change From Baseline in Mean Monthly Migraine Days (MMD) Over Months 4, 5, and 6 of the Double-blind Treatment Period	-1.98 migraine days / month Interval -2.72 to -1.24	-3.60 migraine days / month Interval -4.36 to -2.85

SECONDARY outcome

Timeframe: 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period

Population: Efficacy analysis set; participants with missing data were counted as non-responders.

Outcome measures

Outcome measures
Measure	Placebo QM n=131 Participants Participants received placebo once a month for 24 weeks during the double-blind treatment period.	Erenumab 70 mg QM n=130 Participants Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period.
Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days Over Months 4, 5, and 6 of the DBTP	16.8 percentage of participants	31.5 percentage of participants

SECONDARY outcome

Timeframe: 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period

Population: Efficacy analysis set; observed data

An acute migraine-specific medication treatment day is any calendar day during which a participant took a migraine-specific medication (e.g., triptan or ergotamine). The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment period minus the number of migraine-specific treatment days during the 4-week baseline period.

Outcome measures

Outcome measures
Measure	Placebo QM n=128 Participants Participants received placebo once a month for 24 weeks during the double-blind treatment period.	Erenumab 70 mg QM n=129 Participants Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period.
Change From Baseline in Mean Monthly Acute Migraine-specific Medication Treatment Days Over Months 4, 5, and 6 of the DBTP	-1.10 days / month Interval -1.74 to -0.46	-2.57 days / month Interval -3.21 to -1.93

Adverse Events

Double-blind Treatment Period: Placebo QM

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

Double-blind Treatment Period: Erenumab 70 mg QM

Serious events: 2 serious events

Other events: 44 other events

Deaths: 0 deaths

Open-label Treatment Period: Erenumab 70 mg QM

Serious events: 7 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Double-blind Treatment Period: Placebo QM n=131 participants at risk Participants received placebo once a month for 24 weeks during the double-blind treatment period.	Double-blind Treatment Period: Erenumab 70 mg QM n=130 participants at risk Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period.	Open-label Treatment Period: Erenumab 70 mg QM n=254 participants at risk Participants received erenumab 70 mg once a month for 28 weeks during the open-label treatment period.
Musculoskeletal and connective tissue disorders Back pain	4.6% 6/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	5.4% 7/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	2.4% 6/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Gastrointestinal disorders Constipation	1.5% 2/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	4.6% 6/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	5.1% 13/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Infections and infestations Nasopharyngitis	28.2% 37/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	26.9% 35/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	19.3% 49/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

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	Double-blind Treatment Period: Placebo QM n=131 participants at risk Participants received placebo once a month for 24 weeks during the double-blind treatment period.	Double-blind Treatment Period: Erenumab 70 mg QM n=130 participants at risk Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period.	Open-label Treatment Period: Erenumab 70 mg QM n=254 participants at risk Participants received erenumab 70 mg once a month for 28 weeks during the open-label treatment period.
Infections and infestations Appendicitis	0.76% 1/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Injury, poisoning and procedural complications Brain contusion	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.77% 1/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.77% 1/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Injury, poisoning and procedural complications Skull fracture	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.77% 1/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Injury, poisoning and procedural complications Wound	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.77% 1/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.77% 1/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.76% 1/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.77% 1/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Infections and infestations Tonsillitis	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.39% 1/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Injury, poisoning and procedural complications Foot fracture	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.39% 1/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.39% 1/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.39% 1/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.39% 1/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.39% 1/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.39% 1/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/131 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.00% 0/130 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).	0.39% 1/254 • DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).