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A Study to Evaluate the Tolerability of Botox and Topiramate or Botox and Placebo and Effect on Cognitive Efficiency

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ClinicalTrials.gov Identifier: NCT01700387
Recruitment Status : Completed
First Posted : October 4, 2012
Results First Posted : October 13, 2014
Last Update Posted : February 21, 2018
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Cady, Roger, M.D.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Chronic Migraine
Interventions Drug: onabotulinumtoxinA
Drug: Topiramate
Drug: Placebo
Enrollment 20
Recruitment Details  
Pre-assignment Details  
Arm/Group Title OnabotulinumtoxinA + Topiramate OnabotulinumtoxinA + Placebo
Hide Arm/Group Description

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:

Week 1: topiramate 25 mg qhs (every night at bedtime) Week 2: topiramate 25 mg bid (twice a day) Week 3: topiramate 25 mg q am (every day before noon) + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:

Week 1: 1 tab qhs (every night at bedtime) Week 2: 1 tab bid (twice daily) Week 3: 1 tab q am (every day before noon) + 2 tabs qhs Week 4: 2 tabs bid

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Period Title: Overall Study
Started 10 10
Completed 6 6
Not Completed 4 4
Reason Not Completed
Withdrawal by Subject             1             2
Adverse Event             1             1
Lost to Follow-up             2             1
Arm/Group Title OnabotulinumtoxinA + Topiramate OnabotulinumtoxinA + Placebo Total
Hide Arm/Group Description

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:

Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:

Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Total of all reporting groups
Overall Number of Baseline Participants 10 10 20
Hide Baseline Analysis Population Description
Only those subjects which randomized were included in the baseline analysis.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 20 participants
40.84  (15.98) 39.51  (6.99) 40.18  (12.02)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Female
9
  90.0%
10
 100.0%
19
  95.0%
Male
1
  10.0%
0
   0.0%
1
   5.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
10
 100.0%
9
  90.0%
19
  95.0%
Unknown or Not Reported
0
   0.0%
1
  10.0%
1
   5.0%
1.Primary Outcome
Title Subject Attrition Post Randomization
Hide Description Count of subject attrition following randomization and reason for attrition (Consent withdrawn, Withdrawn due to adverse event, Lost to follow up)
Time Frame Collected on Visit 2 (Day 29) through Visit 6 (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title OnabotulinumtoxinA + Topiramate OnabotulinumtoxinA + Placebo
Hide Arm/Group Description:

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:

Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:

Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Overall Number of Participants Analyzed 10 10
Measure Type: Number
Unit of Measure: participants
Consent Withdrawn 1 2
Withdrawn Due to Adverse Event 1 1
Lost to Follow Up 2 1
2.Primary Outcome
Title Subject Global Impression of Change (SGIC)
Hide Description Score on Subject Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.
Time Frame Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.
Arm/Group Title OnabotulinumtoxinA + Topiramate OnabotulinumtoxinA + Placebo
Hide Arm/Group Description:

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:

Week 1: topiramate 25 mg q hs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50mg q hs Week 4: topiramate 50mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:

Week 1: 1 tab q hs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs q hs Week 4: 2 tabs bid

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Overall Number of Participants Analyzed 8 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Visit 3 (n = 8,10) 5.38  (1.19) 5.30  (1.25)
Visit 4 (n = 6,9) 6.33  (0.82) 5.77  (1.09)
Visit 5 (n = 6,6) 6.66  (0.52) 6.17  (1.17)
Visit 6 (n = 6,6) 7.00  (0.00) 6.00  (1.26)
3.Primary Outcome
Title Physician Global Impression of Change (PGIC)
Hide Description Score on Physician Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.
Time Frame Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants vary at each visit based on the number of those still enrolled in the study at the time of the visit.
Arm/Group Title OnabotulinumtoxinA + Topiramate OnabotulinumtoxinA + Placebo
Hide Arm/Group Description:

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:

Week 1: topiramate 25 mg q hs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50mg q hs Week 4: topiramate 50mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:

Week 1: 1 tab q hs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs q hs Week 4: 2 tabs bid

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Overall Number of Participants Analyzed 8 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Visit 3 (n = 8,10) 5.25  (1.16) 5.30  (1.25)
Visit 4 (n = 6,9) 5.40  (1.34) 5.89  (0.93)
Visit 5 (n = 6,6) 6.67  (0.52) 5.83  (1.94)
Visit 6 (n = 6,6) 6.83  (0.41) 5.83  (1.47)
4.Primary Outcome
Title Subject's Mental Efficiency Workload Test (MEWT) Overall Performance Index (PI) Score at Visits 2-6 to Measure Cognitive Efficiency
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
5.Primary Outcome
Title Subject's Controlled Oral Word Association Test (COWAT) Scores at Visits 2-6 to Measure Cognitive Efficiency
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Change in Number of Headache Days Reported in 30-day Baseline Period vs. Treatment Period Months 1-12
Hide Description [Not Specified]
Time Frame 13 Months
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Subject's Headache Impact Test (HIT-6) Scores at Visits 2-6 to Measure Effect of Headache in Subject's Life
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
8.Secondary Outcome
Title MEWT Score for Simple Reaction Time Sub-test at Visits 2-6 to Measure Mental Efficiency
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
9.Secondary Outcome
Title MEWT Score for Running Memory Continuous Performance Task Sub-test at Visits 2-6 to Measure Mental Efficiency
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
10.Secondary Outcome
Title MEWT Scores for Matching to Sample Sub-test at Visit 2-6 to Measure Mental Efficiency
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
11.Secondary Outcome
Title MEWT Scores for Mathematical Processing Sub-test at Visits 2-6 to Measure Mental Efficiency
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Subject Estimation of Compliance With Daily Topiramate
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Pharmacoeconomic Estimates on Number of Patients Needed to Treat (Randomize) to Have One Successful Patient at 3, 6, 9, and 12 Months.
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Hide Description [Not Specified]
Time Frame 13 Months
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Subject's Migraine Specific Quality of Life Questionnaire (MSQ) Scores at Baseline, 3, 6, 9 and 12 Months to Measure Subject's Quality of Life
Hide Description [Not Specified]
Time Frame 12 Months
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OnabotulinumtoxinA + Topiramate OnabotulinumtoxinA + Placebo
Hide Arm/Group Description

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:

Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:

Week 1: 1 tab qhs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs qhs Week 4: 2 tabs bid

onabotulinumtoxinA: All subjects will receive a minimum dose of 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas at Visits 2-5.

All-Cause Mortality
OnabotulinumtoxinA + Topiramate OnabotulinumtoxinA + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
OnabotulinumtoxinA + Topiramate OnabotulinumtoxinA + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/10 (30.00%)      0/10 (0.00%)    
Cardiac disorders     
Cardiac Arrest  1/10 (10.00%)  1 0/10 (0.00%)  0
Gastrointestinal disorders     
Rectal Proplapse  1/10 (10.00%)  1 0/10 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1/10 (10.00%)  1 0/10 (0.00%)  0
Infections and infestations     
Septic Shock  1/10 (10.00%)  1 0/10 (0.00%)  0
Renal and urinary disorders     
Renal Failure  1/10 (10.00%)  1 0/10 (0.00%)  0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
OnabotulinumtoxinA + Topiramate OnabotulinumtoxinA + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/10 (80.00%)      6/10 (60.00%)    
Gastrointestinal disorders     
Nausea  3/10 (30.00%)  4 3/10 (30.00%)  3
General disorders     
Vertigo  2/10 (20.00%)  3 4/10 (40.00%)  5
Nervous system disorders     
Decreased Cognition  5/10 (50.00%)  6 1/10 (10.00%)  1
Respiratory, thoracic and mediastinal disorders     
Sinus Infection  1/10 (10.00%)  1 3/10 (30.00%)  3
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Roger Cady
Organization: Clinvest/A Division of Banyan Group Inc.
Phone: 417-883-7889
Responsible Party: Cady, Roger, M.D.
ClinicalTrials.gov Identifier: NCT01700387     History of Changes
Other Study ID Numbers: 12-001AL
71403 ( Other Grant/Funding Number: Allergan )
First Submitted: October 1, 2012
First Posted: October 4, 2012
Results First Submitted: October 7, 2014
Results First Posted: October 13, 2014
Last Update Posted: February 21, 2018