Trial Outcomes & Findings for A Long-term Efficacy, Safety, and Tolerability Study of BOTOX® in Patients With Chronic Migraine (NCT NCT01516892)
NCT ID: NCT01516892
Last Updated: 2017-01-06
Results Overview
Mean change from Baseline in frequency (number) of headache days during the 28 day period ending with Week 108. A headache day was defined as a day (00:00 to 23:59) for which the participant reported a headache in the patient diary with 4 or more continuous hours of headache. A negative change from Baseline indicates improvement.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
716 participants
Primary outcome timeframe
Baseline, Week 108
Results posted on
2017-01-06
Participant Flow
Participant milestones
| Measure |
BOTOX®
Participants received 155 U of onabotulinumtoxinA (BOTOX®) approximately every 12 weeks for 108 weeks. OnabotulinumtoxinA was administered as 31 intramuscular injections in 7 head/neck muscle areas.
|
|---|---|
|
Overall Study
STARTED
|
716
|
|
Overall Study
COMPLETED
|
373
|
|
Overall Study
NOT COMPLETED
|
343
|
Reasons for withdrawal
| Measure |
BOTOX®
Participants received 155 U of onabotulinumtoxinA (BOTOX®) approximately every 12 weeks for 108 weeks. OnabotulinumtoxinA was administered as 31 intramuscular injections in 7 head/neck muscle areas.
|
|---|---|
|
Overall Study
Adverse Event
|
25
|
|
Overall Study
Lack of Efficacy
|
35
|
|
Overall Study
Pregnancy
|
5
|
|
Overall Study
Lost to Follow-up
|
82
|
|
Overall Study
Subject Withdrew Consent
|
92
|
|
Overall Study
Protocol Violation
|
60
|
|
Overall Study
Other Miscellaneous Reasons
|
43
|
|
Overall Study
Missing
|
1
|
Baseline Characteristics
A Long-term Efficacy, Safety, and Tolerability Study of BOTOX® in Patients With Chronic Migraine
Baseline characteristics by cohort
| Measure |
BOTOX®
n=716 Participants
Participants received 155 U of onabotulinumtoxinA (BOTOX®) approximately every 12 weeks for 108 weeks. OnabotulinumtoxinA was administered as 31 intramuscular injections in 7 head/neck muscle areas.
|
|---|---|
|
Age, Customized
< 40 years
|
270 participants
n=99 Participants
|
|
Age, Customized
≥ 40 years
|
446 participants
n=99 Participants
|
|
Gender
Female
|
607 Participants
n=99 Participants
|
|
Gender
Male
|
109 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 108Population: Analysis Population included all enrolled participants who had at least one efficacy assessment at baseline or a post-baseline visit.
Mean change from Baseline in frequency (number) of headache days during the 28 day period ending with Week 108. A headache day was defined as a day (00:00 to 23:59) for which the participant reported a headache in the patient diary with 4 or more continuous hours of headache. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
BOTOX®
n=715 Participants
Participants received 155 U of onabotulinumtoxinA (BOTOX®) approximately every 12 weeks for 108 weeks. OnabotulinumtoxinA was administered as 31 intramuscular injections in 7 head/neck muscle areas.
|
|---|---|
|
Change From Baseline in the Frequency of Headache Days
Baseline
|
22.0 headache days
Standard Deviation 4.82
|
|
Change From Baseline in the Frequency of Headache Days
Change from Baseline at Week 108
|
-10.7 headache days
Standard Deviation 6.44
|
SECONDARY outcome
Timeframe: Baseline, Week 60Population: Analysis Population included all enrolled participants who had at least one efficacy assessment at baseline or a post-baseline visit.
Mean change from Baseline in frequency (number) of headache days during the 28 day period ending with Week 60. A headache day was defined as a day (00:00 to 23:59) for which the participant reported a headache in the patient diary with 4 or more continuous hours of headache. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
BOTOX®
n=715 Participants
Participants received 155 U of onabotulinumtoxinA (BOTOX®) approximately every 12 weeks for 108 weeks. OnabotulinumtoxinA was administered as 31 intramuscular injections in 7 head/neck muscle areas.
|
|---|---|
|
Change From Baseline in the Frequency of Headache Days
Baseline
|
22.0 headache days
Standard Deviation 4.82
|
|
Change From Baseline in the Frequency of Headache Days
Change from Baseline at Week 60
|
-9.2 headache days
Standard Deviation 6.22
|
SECONDARY outcome
Timeframe: Baseline, Week 60, Week 108Population: Participants from the Analysis Population, all enrolled participants who had at least one efficacy assessment at baseline or a post-baseline visit, with data available for analysis.
The HIT-6 measures the impact of headache and treatment on the participant's functional health and well-being in 6 domains: pain; role functioning (ability to carry out usual activities); social functioning; energy or fatigue; cognition; and emotional distress assessed over the prior 4-week period. The total possible score ranges from 36 (no impact) to 78 (worst impact). A negative change from Baseline indicates an improvement, and a positive change from Baseline indicates a worsening.
Outcome measures
| Measure |
BOTOX®
n=713 Participants
Participants received 155 U of onabotulinumtoxinA (BOTOX®) approximately every 12 weeks for 108 weeks. OnabotulinumtoxinA was administered as 31 intramuscular injections in 7 head/neck muscle areas.
|
|---|---|
|
Change From Baseline in Headache Impact Test Questionnaire (HIT-6) Total Score
Baseline
|
64.7 score on a scale
Standard Deviation 4.82
|
|
Change From Baseline in Headache Impact Test Questionnaire (HIT-6) Total Score
Change from Baseline at Week 60
|
-6.8 score on a scale
Standard Deviation 6.55
|
|
Change From Baseline in Headache Impact Test Questionnaire (HIT-6) Total Score
Change from Baseline at Week 108
|
-7.1 score on a scale
Standard Deviation 7.24
|
Adverse Events
BOTOX®
Serious events: 75 serious events
Other events: 75 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BOTOX®
n=716 participants at risk
Participants received 155 U of onabotulinumtoxinA (BOTOX®) approximately every 12 weeks for 108 weeks. OnabotulinumtoxinA was administered as 31 intramuscular injections in 7 head/neck muscle areas.
|
|---|---|
|
Cardiac disorders
Aortic valve incompetence
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Cardiac disorders
Atrial fibrillation
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Cardiac disorders
Congestive cardiomyopathy
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Cardiac disorders
Myocardial infarction
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Endocrine disorders
Cushing's syndrome
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Eye disorders
Cataract subcapsular
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Gastrointestinal disorders
Colonic polyp
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Gastrointestinal disorders
Constipation
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Gastrointestinal disorders
Gastritis
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
General disorders
Chest discomfort
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
General disorders
Device intolerance
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
General disorders
Fatigue
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
General disorders
Non-cardiac chest pain
|
0.42%
3/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
General disorders
Pyrexia
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Immune system disorders
Anaphylactic reaction
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Infections and infestations
Appendicitis
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Infections and infestations
Bronchitis
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Infections and infestations
Gastrointestinal infection
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Infections and infestations
Influenza
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Infections and infestations
Meningitis viral
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Infections and infestations
Pneumonia
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Infections and infestations
Pyelonephritis acute
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Infections and infestations
Sinusitis
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Fall
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Head injury
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Ligament injury
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.28%
2/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Metabolism and nutrition disorders
Obesity
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Investigations
Electrocardiogram abnormal
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.28%
2/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Musculoskeletal and connective tissue disorders
Periarthritis
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.28%
2/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Angiomyolipoma
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Extranodal marginal zone B-cell lymphoma (MALT type)
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.42%
3/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mantle cell lymphoma
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Convulsion
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Diabetic hyperosmolar coma
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Dizziness
|
0.28%
2/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Headache
|
0.42%
3/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Hypoaesthesia
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Intracranial hypotension
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Loss of consciousness
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Migraine
|
0.84%
6/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Paraesthesia
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Presyncope
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Syncope
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Tension headache
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Psychiatric disorders
Bipolar disorder
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Psychiatric disorders
Depression
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Psychiatric disorders
Major depression
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Psychiatric disorders
Panic attack
|
0.28%
2/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Psychiatric disorders
Suicidal ideation
|
0.70%
5/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Renal and urinary disorders
Calculus ureteric
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Reproductive system and breast disorders
Dysfunctional uterine bleeding
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Surgical and medical procedures
Cholecystectomy
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Surgical and medical procedures
Hysterectomy
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Vascular disorders
Thrombosis
|
0.14%
1/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
Other adverse events
| Measure |
BOTOX®
n=716 participants at risk
Participants received 155 U of onabotulinumtoxinA (BOTOX®) approximately every 12 weeks for 108 weeks. OnabotulinumtoxinA was administered as 31 intramuscular injections in 7 head/neck muscle areas.
|
|---|---|
|
Infections and infestations
Sinusitis
|
5.2%
37/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.3%
38/716 • 108 Weeks
Safety population included all participants who received at least one BOTOX® treatment injection.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A disclosure restriction on the PI is that results publication or presentations be submitted for sponsor review no less than 90 days in advance, during which the sponsor can embargo such communications prior to public release. The embargo may be extended for up to 90 days for the sponsor to preserve its proprietary rights. PI will not publish study results prior to release of a multicenter manuscript including data from all study centers. The sponsor cannot require changes to the communication.
- Publication restrictions are in place
Restriction type: OTHER