Trial Outcomes & Findings for Efficacy and Safety of BI 655066/ABBV-066 (Risankizumab) in Patients With Severe Persistent Asthma (NCT NCT02443298)

Last Updated: 2019-04-10

Results Overview

Time to first asthma worsening during the planned 24 week treatment period: Asthma worsening was defined as the occurrence of any one of the following four criteria: a) Decrease from baseline of ≥30% in morning peak expiratory flow (PEF) on at least 2 consecutive days. b) Increase from baseline of ≥50% and an increase of least 4 puffs in daily use of rescue medication for at least 2 consecutive days. c) Increase from baseline of ≥0.75 units in ACQ5. d) Severe asthma exacerbations defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

214 participants

Primary outcome timeframe

24 weeks

Results posted on

2019-04-10

Participant Flow

This was a randomized, double-blind, placebo-controlled, parallel-group multicenter study to assess the efficacy and safety of risankizumab, an IL-23p19 monoclonal antibody, compared to placebo in patients with severe persistent asthma.

All patients were screened for eligibility to participate in the trial. Patients attended a specialist sites which ensured that they (the patients) met all strictly implemented inclusion/exclusion criteria. Patients were not to be randomized to trial treatment if any one of the specific entry criteria was violated.

Participant milestones

Participant milestones
Measure	Risankizumab Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Overall Study STARTED	105	109
Overall Study COMPLETED	101	104
Overall Study NOT COMPLETED	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Risankizumab Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Overall Study Adverse Event	3	3
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

Efficacy and Safety of BI 655066/ABBV-066 (Risankizumab) in Patients With Severe Persistent Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Risankizumab n=105 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Total n=214 Participants Total of all reporting groups
Age, Continuous	54.1 Years STANDARD_DEVIATION 11.3 • n=99 Participants	52.3 Years STANDARD_DEVIATION 12.5 • n=107 Participants	53.2 Years STANDARD_DEVIATION 11.9 • n=206 Participants
Sex: Female, Male Female	69 Participants n=99 Participants	64 Participants n=107 Participants	133 Participants n=206 Participants
Sex: Female, Male Male	36 Participants n=99 Participants	45 Participants n=107 Participants	81 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	102 Participants n=99 Participants	106 Participants n=107 Participants	208 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	11 Participants n=99 Participants	11 Participants n=107 Participants	22 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	9 Participants n=99 Participants	8 Participants n=107 Participants	17 Participants n=206 Participants
Race (NIH/OMB) White	84 Participants n=99 Participants	88 Participants n=107 Participants	172 Participants n=206 Participants
Race (NIH/OMB) More than one race	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Oral corticosteroid (OCS) use at baseline Yes	15 Participants n=99 Participants	17 Participants n=107 Participants	32 Participants n=206 Participants
Oral corticosteroid (OCS) use at baseline No	90 Participants n=99 Participants	92 Participants n=107 Participants	182 Participants n=206 Participants
Baseline Morning peak expiratory flow (PEF)	299.34 Liter/Minute (L/min) STANDARD_DEVIATION 110.50 • n=99 Participants	309.56 Liter/Minute (L/min) STANDARD_DEVIATION 115.34 • n=107 Participants	304.54 Liter/Minute (L/min) STANDARD_DEVIATION 112.84 • n=206 Participants
Baseline 24 Hour Rescue Medication Use	3.17 Puff STANDARD_DEVIATION 3.81 • n=99 Participants	3.89 Puff STANDARD_DEVIATION 4.78 • n=107 Participants	3.53 Puff STANDARD_DEVIATION 4.34 • n=206 Participants
Baseline First 5 questions of the Asthma Control Questionnaire (ACQ5) Score	2.15 Unit on scale STANDARD_DEVIATION 1.15 • n=99 Participants	2.39 Unit on scale STANDARD_DEVIATION 1.17 • n=107 Participants	2.27 Unit on scale STANDARD_DEVIATION 1.17 • n=206 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment.

Outcome measures

Outcome measures
Measure	Risankizumab n=105 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Time to First Asthma Worsening During the Planned 24 Week Treatment Period	40.00 Days Interval 30.0 to 52.0	85.50 Days Interval 63.0 to 131.0

SECONDARY outcome

Timeframe: 24 weeks

Population: Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment.

Time to first asthma worsening during the planned 24 week treatment period according to alternative definition: Asthma worsening was defined as the occurrence of any one of the following four criteria: a) Decrease from baseline of ≥30% in morning peak expiratory flow (PEF) on at least 2 consecutive days. b) Increase from baseline of ≥50% and an increase of least 4 puffs in daily use of rescue medication for at least 2 consecutive days. c) Increase from baseline of ≥0.5 units in ACQ5. d) Severe asthma exacerbations defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation.

Outcome measures

Outcome measures
Measure	Risankizumab n=105 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Time to First Asthma Worsening During the Planned 24 Week Treatment Period According to Alternative Definition	20.00 Days Interval 16.0 to 25.0	37.00 Days Interval 31.0 to 45.0

SECONDARY outcome

Timeframe: 24 weeks

Population: Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment.

Annualized rate of asthma worsening during the planned 24 week treatment period. Asthma worsening was defined as the occurrence of any one of the following four criteria: a) Decrease from baseline of ≥30% in morning peak expiratory flow (PEF) on at least 2 consecutive days. b) Increase from baseline of ≥50% and an increase of least 4 puffs in daily use of rescue medication for at least 2 consecutive days. c) Increase from baseline of ≥0.75 units in ACQ5. d) Severe asthma exacerbations defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation. Mean is Annualized rate.

Outcome measures

Outcome measures
Measure	Risankizumab n=105 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Annualized Rate of Asthma Worsening During the Planned 24 Week Treatment Period	4.8412 Events per patient year Standard Error 0.577	3.2410 Events per patient year Standard Error 0.401

SECONDARY outcome

Timeframe: 24 weeks

Population: Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment. NA = not estimable due to an insufficient numbers of patient with an event

Time to first severe asthma exacerbation during the planned 24 week treatment period. Severe asthma exacerbation was defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation.

Outcome measures

Outcome measures
Measure	Risankizumab n=105 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Time to First Severe Asthma Exacerbation During the Planned 24 Week Treatment Period	NA Days Not estimable due to an insufficient numbers of patient with an event	NA Days Not estimable due to an insufficient numbers of patient with an event

SECONDARY outcome

Timeframe: 24 weeks

Population: Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment.

Annualized rate of severe asthma exacerbation during the planned 24-week treatment period. Severe asthma exacerbation was defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation. Mean is Annualized rate.

Outcome measures

Outcome measures
Measure	Risankizumab n=105 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Annualized Rate of Severe Asthma Exacerbation During the Planned 24-week Treatment Period	1.5901 Events per patient year Standard Error 0.257	1.4051 Events per patient year Standard Error 0.228

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment. One patient not included in the analysis due to missing baseline value. Number of patients with either baseline or on-treatment data at the respective week and does not require having both.

Trough forced expiratory volume in 1 second (FEV1) in-clinic change from baseline at week 24.

Outcome measures

Outcome measures
Measure	Risankizumab n=105 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Trough Forced Expiratory Volume in 1 Second (FEV1) In-clinic Change From Baseline at Week 24	-0.052 Liter (L) Standard Error 0.036	-0.013 Liter (L) Standard Error 0.035

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: FAS: All randomized patients who received at least one dose of treatment. One patient not included in the analysis due to missing baseline value and one patient not included in the analysis due to missing on-treatment data. Number of patients with either baseline or on-treatment data at the respective week and does not require having both.

Post-bronchodilator forced expiratory volume in 1 second (FEV1) in-clinic change from baseline at week 24.

Outcome measures

Outcome measures
Measure	Risankizumab n=105 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) In-clinic Change From Baseline at Week 24	-0.097 Liter (L) Standard Error 0.032	-0.030 Liter (L) Standard Error 0.032

SECONDARY outcome

Timeframe: 24 weeks

Population: Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment. Ten patients excluded from the analysis due to missing data at week 24.

The score at week 24 is the average of the responses to the five ACQ5 questions for the week preceding the Week 24 visit. The ACQ5 asks patients to rate the severity of their asthma symptoms and the degree to which asthma affected their sleep and other daily activities. The scale for all five ACQ5 questions range from the best possible answer of 0 (No symptoms, None, Never) to the worst possible answer of 6 (very severe, unable to sleep, totally limited). The ACQ5 score can range from 0.0 (best) to 6.0 (worst).

Outcome measures

Outcome measures
Measure	Risankizumab n=105 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 Participants Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Weekly Asthma Control Questionaire Score at Week 24	1.857 Unit on Scale Standard Error 0.099	1.708 Unit on Scale Standard Error 0.099

Adverse Events

Risankizumab

Serious events: 14 serious events

Other events: 84 other events

Deaths: 0 deaths

Placebo

Serious events: 21 serious events

Other events: 80 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Risankizumab n=105 participants at risk Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 participants at risk Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Infections and infestations Bronchitis	10.5% 11/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	8.3% 9/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Nasopharyngitis	10.5% 11/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	20.2% 22/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Sinusitis	5.7% 6/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	2.8% 3/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Upper respiratory tract infection	8.6% 9/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	9.2% 10/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Urinary tract infection	4.8% 5/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	5.5% 6/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Investigations Blood creatine phosphokinase increased	8.6% 9/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	2.8% 3/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	5.5% 6/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Nervous system disorders Headache	6.7% 7/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	5.5% 6/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Respiratory, thoracic and mediastinal disorders Asthma	61.9% 65/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	53.2% 58/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.7% 6/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	6.4% 7/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.

Additional Information

Global Medical Services

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Phone: 1-800-633-9110

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Risankizumab n=105 participants at risk Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)	Placebo n=109 participants at risk Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20)
Ear and labyrinth disorders Sudden hearing loss	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.00% 0/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Immune system disorders Anaphylactic reaction	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Appendicitis	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Arthritis bacterial	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Chronic sinusitis	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Epstein-Barr virus infection	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.00% 0/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Localised infection	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Pneumonia	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	1.8% 2/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Respiratory syncytial virus infection	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.00% 0/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Infections and infestations Urosepsis	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Investigations Electrocardiogram T wave abnormal	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.00% 0/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Nervous system disorders Dyskinesia	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Nervous system disorders Multiple sclerosis	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.00% 0/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Nervous system disorders Transient ischaemic attack	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Psychiatric disorders Anxiety	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.00% 0/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Psychiatric disorders Depression	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Renal and urinary disorders Hydronephrosis	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Renal and urinary disorders Nephrolithiasis	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Respiratory, thoracic and mediastinal disorders Asthma	5.7% 6/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	4.6% 5/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Respiratory, thoracic and mediastinal disorders Asthmatic crisis	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.95% 1/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.00% 0/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.00% 0/105 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.	0.92% 1/109 • From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.