A Long-term Efficacy, Safety, and Tolerability Study of BOTOX® in Patients With Chronic Migraine

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01516892
• Collaborator: (none)
• Enrollment: 716
• Locations: 32
• Arm: 1
• Duration (Months): 47
• Patients Per Site: 22.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This open-label study will assess the long-term efficacy, safety, and tolerability of onabotulinumtoxinA administered for prophylaxis of headaches in patients with chronic migraine.

Condition or Disease	Intervention/Treatment	Phase
Migraine Disorders	Biological: onabotulinumtoxinA	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 716 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: onabotulinumtoxinA; Participants received 155 U of onabotulinumtoxinA approximately every 12 weeks for 108 weeks. OnabotulinumtoxinA was administered as 31 intramuscular injections in 7 head/neck muscle areas.; Other Names: BOTOX® botulinum toxin Type A

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Frequency of Headache Days [Baseline, Week 108]

   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.

Secondary Outcome Measures

1. Change From Baseline in the Frequency of Headache Days [Baseline, Week 60]

   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.

2. Change From Baseline in Headache Impact Test Questionnaire (HIT-6) Total Score [Baseline, Week 60, Week 108]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of chronic migraine (≥15 days per month with headache lasting 4 hours a day or longer)

Exclusion Criteria:

• Diagnosis of myasthenia gravis, Eaton-Lambert Syndrome, or amyotrophic lateral sclerosis

• Headache attributed to another disorder

• Infection or skin disorder at injection sites

• Previous treatment with botulinum toxin of any serotype for any reason

• Anticipated need for botulinum toxin of any type for any reason during the course of the study

• Previous participation in any botulinum toxin clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Neurological Institute	Scottsdale	Arizona	United States	85255-7450
2	The Research Center of Southern California, LLC	Encinitas	California	United States	92024
3	USC Neurology	Los Angeles	California	United States	90033
4	UCSF Headache Center	San Francisco	California	United States	94133
5	Neurological Research Institute	Santa Monica	California	United States	90404
6	Advanced Neurosciences Research, LLC	Fort Collins	Colorado	United States	80528
7	Tampa General Hospital	Tampa	Florida	United States	33606
8	Premiere Research Institute at Palm Beach Neurology	West Palm Beach	Florida	United States	33407
9	Robbins Headache Clinic	Northbrook	Illinois	United States	60062
10	Mid-Atlantic Headache Institute	Baltimore	Maryland	United States	21208
11	Kaiser Permanente Research Office/Neurology Department	Largo	Maryland	United States	20774
12	Clinvest Research	Springfield	Missouri	United States	65807-6988
13	Mercy Health Research	St. Louis	Missouri	United States	63141
14	Renown Institute for Neurosciences	Reno	Nevada	United States	89502
15	Dent Neurologic Institute	Amherst	New York	United States	14226
16	Montefiore Medical Center	Bronx	New York	United States	10461
17	Headache Wellness Center	Greensboro	North Carolina	United States	27405
18	Ohio Clinical Research Partners, LLC	Canton	Ohio	United States	44718
19	Jefferson University Hospitals	Philadelphia	Pennsylvania	United States	19107
20	Wesley Headache Clinic	Cordova	Tennessee	United States	38018
21	Baylor Research Institute	Dallas	Texas	United States	75231
22	Dr. Joseph Frasca	Adelaide		Australia	SA 5000
23	Dr. Con Yiannikas	Burwood		Australia	NSW 2134
24	Associate Professor Richard Stark	Melbourne		Australia	VIC 3000
25	Richmmond Neurology	Richmond		Australia	VIC 3051
26	Associate Professor John O'Sullivan	Spring Hill		Australia	QLD 4000
27	Hallym University Sacred Heart Hospital	Dongan-gu, Anyang	Anyang Gyeonggi-do	Korea, Republic of
28	Uijeongbu St. Mary's Hospital	Uijeongbu Si	Gyeonggi-Do	Korea, Republic of
29	Kangbuk Samsung Hospital	Jongno-Gu	Seoul	Korea, Republic of
30	Seoul St. Mary's Hospital	Jongno-Gu	Seoul	Korea, Republic of
31	Seoul Eulji Hospital	Nowon-Gu	Seoul	Korea, Republic of
32	Yonsei University Dental Hospital	Seodaemum-Gu	Seoul	Korea, Republic of

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01516892
• Other Study ID Numbers: GMA-BTX-CM-10-001; The COMPEL Study
• First Posted: Jan 25, 2012
• Last Update Posted: Jan 6, 2017
• Last Verified: Nov 1, 2016

• Additional relevant MeSH terms: Migraine Disorders; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	BOTOX®
Arm/Group Description	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.
Period Title: Overall Study
STARTED	716
COMPLETED	373
NOT COMPLETED	343

Baseline Characteristics

Arm/Group Title	BOTOX®
Arm/Group Description	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 Participants	716
Age, Customized (participants) [Number]
< 40 years	270 37.7%
≥ 40 years	446 62.3%
Gender (Count of Participants)
Female	607 84.8%
Male	109 15.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Frequency of Headache Days
Description	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.
Time Frame	Baseline, Week 108

Outcome Measure Data

Analysis Population Description

Analysis Population included all enrolled participants who had at least one efficacy assessment at baseline or a post-baseline visit.

Arm/Group Title	BOTOX®
Arm/Group Description	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.
Measure Participants	715
Baseline	22.0 (4.82)
Change from Baseline at Week 108	-10.7 (6.44)

2. Secondary Outcome

Title	Change From Baseline in the Frequency of Headache Days
Description	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.
Time Frame	Baseline, Week 60

Outcome Measure Data

Analysis Population Description

Analysis Population included all enrolled participants who had at least one efficacy assessment at baseline or a post-baseline visit.

Arm/Group Title	BOTOX®
Arm/Group Description	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.
Measure Participants	715
Baseline	22.0 (4.82)
Change from Baseline at Week 60	-9.2 (6.22)

3. Secondary Outcome

Title	Change From Baseline in Headache Impact Test Questionnaire (HIT-6) Total Score
Description	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.
Time Frame	Baseline, Week 60, Week 108

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	BOTOX®
Arm/Group Description	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.
Measure Participants	713
Baseline	64.7 (4.82)
Change from Baseline at Week 60	-6.8 (6.55)
Change from Baseline at Week 108	-7.1 (7.24)

Adverse Events

Time Frame	108 Weeks
Adverse Event Reporting Description	Safety population included all participants who received at least one BOTOX® treatment injection.
Arm/Group Title	BOTOX®
Arm/Group Description	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.
All Cause Mortality
	BOTOX®
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	BOTOX®
	Affected / at Risk (%)	# Events
Total	75/716 (10.5%)
Cardiac disorders
Aortic valve incompetence	1/716 (0.1%)
Atrial fibrillation	1/716 (0.1%)
Cardiac failure congestive	1/716 (0.1%)
Congestive cardiomyopathy	1/716 (0.1%)
Myocardial infarction	1/716 (0.1%)
Endocrine disorders
Cushing's syndrome	1/716 (0.1%)
Eye disorders
Cataract subcapsular	1/716 (0.1%)
Gastrointestinal disorders
Colitis ischaemic	1/716 (0.1%)
Colonic polyp	1/716 (0.1%)
Constipation	1/716 (0.1%)
Gastritis	1/716 (0.1%)
Hiatus hernia	1/716 (0.1%)
Intestinal obstruction	1/716 (0.1%)
Pancreatitis	1/716 (0.1%)
General disorders
Chest discomfort	1/716 (0.1%)
Device intolerance	1/716 (0.1%)
Fatigue	1/716 (0.1%)
Non-cardiac chest pain	3/716 (0.4%)
Pyrexia	1/716 (0.1%)
Immune system disorders
Anaphylactic reaction	1/716 (0.1%)
Infections and infestations
Appendicitis	1/716 (0.1%)
Bronchitis	1/716 (0.1%)
Gastrointestinal infection	1/716 (0.1%)
Influenza	1/716 (0.1%)
Meningitis viral	1/716 (0.1%)
Pneumonia	1/716 (0.1%)
Pyelonephritis acute	1/716 (0.1%)
Sinusitis	1/716 (0.1%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/716 (0.1%)
Contusion	1/716 (0.1%)
Fall	1/716 (0.1%)
Fibula fracture	1/716 (0.1%)
Head injury	1/716 (0.1%)
Ligament injury	1/716 (0.1%)
Meniscus lesion	1/716 (0.1%)
Procedural pain	2/716 (0.3%)
Rib fracture	1/716 (0.1%)
Tibia fracture	1/716 (0.1%)
Investigations
Electrocardiogram abnormal	1/716 (0.1%)
Metabolism and nutrition disorders
Diabetes mellitus	1/716 (0.1%)
Diabetic ketoacidosis	1/716 (0.1%)
Hypocalcaemia	1/716 (0.1%)
Hypoglycaemia	1/716 (0.1%)
Obesity	1/716 (0.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/716 (0.1%)
Groin pain	1/716 (0.1%)
Intervertebral disc protrusion	2/716 (0.3%)
Periarthritis	1/716 (0.1%)
Rotator cuff syndrome	2/716 (0.3%)
Synovial cyst	1/716 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Angiomyolipoma	1/716 (0.1%)
Basal cell carcinoma	1/716 (0.1%)
Breast cancer	1/716 (0.1%)
Extranodal marginal zone B-cell lymphoma (MALT type)	1/716 (0.1%)
Lung neoplasm malignant	1/716 (0.1%)
Malignant melanoma	3/716 (0.4%)
Mantle cell lymphoma	1/716 (0.1%)
Nervous system disorders
Convulsion	1/716 (0.1%)
Diabetic hyperosmolar coma	1/716 (0.1%)
Dizziness	2/716 (0.3%)
Headache	3/716 (0.4%)
Hypoaesthesia	1/716 (0.1%)
Intracranial hypotension	1/716 (0.1%)
Loss of consciousness	1/716 (0.1%)
Migraine	6/716 (0.8%)
Paraesthesia	1/716 (0.1%)
Presyncope	1/716 (0.1%)
Syncope	1/716 (0.1%)
Tension headache	1/716 (0.1%)
Transient ischaemic attack	1/716 (0.1%)
Psychiatric disorders
Bipolar disorder	1/716 (0.1%)
Depression	1/716 (0.1%)
Major depression	1/716 (0.1%)
Panic attack	2/716 (0.3%)
Suicidal ideation	5/716 (0.7%)
Renal and urinary disorders
Calculus ureteric	1/716 (0.1%)
Nephrolithiasis	1/716 (0.1%)
Reproductive system and breast disorders
Dysfunctional uterine bleeding	1/716 (0.1%)
Ovarian cyst	1/716 (0.1%)
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome	1/716 (0.1%)
Skin and subcutaneous tissue disorders
Rash generalised	1/716 (0.1%)
Surgical and medical procedures
Cholecystectomy	1/716 (0.1%)
Hysterectomy	1/716 (0.1%)
Vascular disorders
Thrombosis	1/716 (0.1%)
Other (Not Including Serious) Adverse Events
	BOTOX®
	Affected / at Risk (%)	# Events
Total	75/ (NaN)
Infections and infestations
Sinusitis	37/716 (5.2%)
Musculoskeletal and connective tissue disorders
Neck pain	38/716 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.