TEAMS: First Add-on vs. Mono-therapy Study of Topiramate in Neuro-Surgical Patients

• Sponsor: Johnson & Johnson Taiwan Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01627860
• Collaborator: (none)
• Enrollment: 55
• Arms: 2
• Duration (Months): 11

Study Details

Study Description

Brief Summary

The purpose of this study is to examine seizure control and tolerability of Topiramate after either transitioning from previous antiepileptic drug (AED) or adding on to previous AED.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Topiramate add-on therapy; Drug: Topiramate monotherapy	Phase 4

Detailed Description

This is a multicenter, randomized (treatment is assigned by chance), open-label (everyone who is involved in the trial knows the study drug), parallel group trial. The study has three phases: a retrospective baseline assessment of patients (4 weeks), titration period (8 weeks) and maintenance period (8 weeks). After qualifying for trial entry in the retrospective baseline phase, eligible patients will be randomized in 1:1 ratio to receive either topiramate add-on therapy or topiramate monotherapy. During the titration period (period in which the dose of the study drug is increased or decreased at the discretion of investigator), topiramate, given as morning doses, will be started with daily doses of 25 mg/day for one week. After that, topiramate will be given as morning and evening doses, and the doses will be gradually increased every week to reach the initial target dose of 200 mg/day at the end of titration period. During the maintenance period, the dose of topiramate could be increased or decreased according to the investigator's judgment. Patients should keep seizure diaries during the 16 weeks of topiramate treated period and are followed with once monthly visits to the clinic, at which safety will be evaluated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Topiramate in the Treatment of Epilepsy: 1st Add-on vs. Mono-therapy Study in Neuro-Surgical Patients
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Topiramate add-on therapy	Drug: Topiramate add-on therapy; Type=range, unit=mg/day, number=25-200, form=tablet, route=oral use.
Experimental: Topiramate monotherapy	Drug: Topiramate monotherapy; Type= range, unit= mg/day, number= 25-200, form= tablet, route= oral use.

Outcome Measures

Primary Outcome Measures

1. Seizure Free Rate: Percentage of Participants Who Did Not Have Any Seizure Episode Within the Last Month of the Maintenance Period (ie, Month 4). [Month 4]

Secondary Outcome Measures

1. Seizure Frequency: Percent Change of Seizure Frequency by the ANCOVA Model During the Month 4 [Baseline (4 weeks retrospective assessment prior to start of titration period) to Month 4]

   Seizure frequency (seizure count/month) was calculated based on the number of seizure within a month. The mean seizure frequency analyzed by the ANCOVA model at each period.

2. Dosage Administration of Topamax During Month 4 [Month 4]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must be diagnosed with seizure disorder

• Have been receiving concomitant therapy with one antiepileptic drug (AED), at stable dose prior to trial entry

• Must be dissatisfied with the current treatment

Exclusion Criteria:

• Have treatable cause of seizures (eg, metabolic disturbance, toxic exposure, an active infection, or neoplasm)

• Have grade IV astrocytomas, eg, Glioblastoma multiforme (GBM) or metastases with progression

• Have seizures occurring only in clustered patterns defined as numerous seizures occurring in less than 30 min

• Have had history (within past six months) of a psychiatric or mood disorder requiring electroconvulsive therapy, major tranquilizers, or monoamine oxidase inhibitors

• Have had schizophrenic or history of exhibiting psychotic symptomatology

• Inability to take medication or maintain a seizure calendar, independently or with assistance

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Johnson & Johnson Taiwan Ltd

Investigators

• Study Director: Janssen-Cilag Taiwan Clinical Trial, Janssen-Cilag Taiwan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johnson & Johnson Taiwan Ltd
• ClinicalTrials.gov Identifier: NCT01627860
• Other Study ID Numbers: CR017248; TOPMATEPY4061; TOP-TWN-MA4
• First Posted: Jun 26, 2012
• Last Update Posted: Oct 29, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Johnson & Johnson Taiwan Ltd: Epilepsy; Topiramate; Neuro-surgical patients; Nervous disorder; Seizures
• Additional relevant MeSH terms: Epilepsy; Topiramate

Study Results

Participant Flow

Recruitment Details	55 participants were randomly assigned to receive either topiramate monotherapy or add-on therapy at 6 sites in Taiwan.

Arm/Group Title	Topiramate Monotherapy	Topiramate add-on Therapy
Arm/Group Description	Participants received a starting dose of 25 mg/day during week 1 and the dosage increased to 50 mg/day in 2 doses during week 2. Consequently, the dosage increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.	Participants received topiramate in addition to previous ant-epileptic drug. Participants received a starting dose of 25 mg/day in the morning during week 1 and the dosage was increased to 50 mg/day in 2 doses (morning and evening) during week 2. Consequently, the dosage was increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage was increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.
Period Title: Overall Study
STARTED	35	20
COMPLETED	23	14
NOT COMPLETED	12	6

Baseline Characteristics

Arm/Group Title	Topiramate Monotherapy	Topiramate add-on Therapy	Total
Arm/Group Description	Participants received a starting dose of 25 mg/day during week 1 and the dosage increased to 50 mg/day in 2 doses during week 2. Consequently, the dosage increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.	Participants received topiramate in addition to previous ant-epileptic drug. Participants received a starting dose of 25 mg/day in the morning during week 1 and the dosage was increased to 50 mg/day in 2 doses (morning and evening) during week 2. Consequently, the dosage was increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage was increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.	Total of all reporting groups
Overall Participants	35	20	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.1 (11.91)	42.4 (12.21)	43.17 (11.41)
Sex: Female, Male (Count of Participants)
Female	13 37.1%	7 35%	20 36.4%
Male	22 62.9%	13 65%	35 63.6%

Outcome Measures

1. Primary Outcome

Title	Seizure Free Rate: Percentage of Participants Who Did Not Have Any Seizure Episode Within the Last Month of the Maintenance Period (ie, Month 4).
Time Frame	Month 4

Outcome Measure Data

Analysis Population Description

Intent-To-Treat population: All randomized participants who received at least one dose of study medication.

Arm/Group Title	Topiramate Monotherapy	Topiramate add-on Therapy
Arm/Group Description	Participants received a starting dose of 25 mg/day during week 1 and the dosage increased to 50 mg/day in 2 doses during week 2. Consequently, the dosage increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.	Participants received topiramate in addition to previous ant-epileptic drug. Participants received a starting dose of 25 mg/day in the morning during week 1 and the dosage was increased to 50 mg/day in 2 doses (morning and evening) during week 2. Consequently, the dosage was increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage was increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.
Measure Participants	35	20
Number [Percentage of participants]	88.57 253.1%	65.00 325%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topiramate Monotherapy, Topiramate add-on Therapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0759
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Seizure free rate
	Estimated Value	23.57
	Confidence Interval	(2-Sided) 95%; -4.21 to 49.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in Seizure free rate (Monotherapy minus Add on therapy)

2. Secondary Outcome

Title	Seizure Frequency: Percent Change of Seizure Frequency by the ANCOVA Model During the Month 4
Description	Seizure frequency (seizure count/month) was calculated based on the number of seizure within a month. The mean seizure frequency analyzed by the ANCOVA model at each period.
Time Frame	Baseline (4 weeks retrospective assessment prior to start of titration period) to Month 4

Outcome Measure Data

Analysis Population Description

Intent-To-Treat population: All randomized participants who received at least one dose of study medication.

Arm/Group Title	Topiramate Monotherapy	Topiramate add-on Therapy
Arm/Group Description	Participants received a starting dose of 25 mg/day during week 1 and the dosage increased to 50 mg/day in 2 doses during week 2. Consequently, the dosage increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.	Participants received topiramate in addition to previous ant-epileptic drug. Participants received a starting dose of 25 mg/day in the morning during week 1 and the dosage was increased to 50 mg/day in 2 doses (morning and evening) during week 2. Consequently, the dosage was increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage was increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.
Measure Participants	35	20
Mean (Standard Deviation) [Percent change]	-55.3 (160)	-75.8 (54.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topiramate Monotherapy, Topiramate add-on Therapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7102
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in mean percent change
	Estimated Value	18.3
	Confidence Interval	(2-Sided) 95%; -81.0 to 117.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in mean percent change of seizure frequency (Monotherapy minus Add on therapy)

3. Secondary Outcome

Title	Dosage Administration of Topamax During Month 4
Time Frame	Month 4

Outcome Measure Data

Analysis Population Description

Participants who have received study medication during month 4.

Arm/Group Title	Topiramate Monotherapy	Topiramate add-on Therapy
Arm/Group Description	Participants received a starting dose of 25 mg/day during week 1 and the dosage increased to 50 mg/day in 2 doses during week 2. Consequently, the dosage increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.	Participants received topiramate in addition to previous ant-epileptic drug. Participants received a starting dose of 25 mg/day in the morning during week 1 and the dosage was increased to 50 mg/day in 2 doses (morning and evening) during week 2. Consequently, the dosage was increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage was increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.
Measure Participants	25	14
Mean (Standard Deviation) [mg]	182.46 (35.63)	178.57 (41.98)

Adverse Events

Time Frame	20 weeks
Arm/Group Title	Topiramate Monotherapy		Topiramate add-on Therapy
Arm/Group Description	Participants received a starting dose of 25 mg/day during week 1 and the dosage increased to 50 mg/day in 2 doses during week 2. Consequently, the dosage increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.		Participants received topiramate in addition to previous ant-epileptic drug. Participants received a starting dose of 25 mg/day in the morning during week 1 and the dosage was increased to 50 mg/day in 2 doses (morning and evening) during week 2. Consequently, the dosage was increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage was increased to 150 mg/day in 2 doses at week 5~6 and 200 mg/day in 2 doses at week 7~8.
All Cause Mortality
	Topiramate Monotherapy		Topiramate add-on Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Topiramate Monotherapy		Topiramate add-on Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/35 (2.9%)		1/20 (5%)
Infections and infestations
Osteomyelitis	1/35 (2.9%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Herniated Intervertebral Disc	0/35 (0%)		1/20 (5%)
Other (Not Including Serious) Adverse Events
	Topiramate Monotherapy		Topiramate add-on Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/35 (94.3%)		20/20 (100%)
Gastrointestinal disorders
Decreased appetite	5/35 (14.3%)		1/20 (5%)
Nausea	3/35 (8.6%)		0/20 (0%)
General disorders
Malaise	3/35 (8.6%)		1/20 (5%)
Investigations
Weight decreased	4/35 (11.4%)		1/20 (5%)
Musculoskeletal and connective tissue disorders
Muscular weakness	2/35 (5.7%)		1/20 (5%)
Nervous system disorders
Dizziness	10/35 (28.6%)		4/20 (20%)
Headache	6/35 (17.1%)		3/20 (15%)
Hypoaesthesia	8/35 (22.9%)		1/20 (5%)
Somnolence	4/35 (11.4%)		2/20 (10%)
Psychiatric disorders
Insomnia	3/35 (8.6%)		2/20 (10%)
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic	3/35 (8.6%)		0/20 (0%)
Skin and subcutaneous tissue disorders
Pruritus	3/35 (8.6%)		2/20 (10%)
Hypoaesthesia facial	4/35 (11.4%)		0/20 (0%)
Hyperhidrosis	1/35 (2.9%)		2/20 (10%)
Rash	3/35 (8.6%)		0/20 (0%)

Limitations/Caveats

No limitations were reported in this study.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.