Fycompa Titration Intervals and Effects on Retention Rate

• Sponsor: University of Arizona (Other)
• Overall Status: Completed
• CT.gov ID: NCT03457129
• Collaborator: Eisai Inc. (Industry)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 43.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study will aim to improve retention and tolerability by slowing the initial titration rate of perampanel from a standard up-titration rate of 2 week intervals to a slower up-titration rate consisting of 3 week intervals. Subjects will be randomized to either perampanel, standard titration interval rate (Group A) or perampanel, slower titration interval rate (Group B).

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Perampanel Oral Tablet	Phase 4

Detailed Description

A total of 60 subjects with a confirmed diagnosis of either partial onset or primary generalized epilepsy will be recruited into the trial. 30 subjects will initiate perampanel at a dose of 2 mg/day and titrate upwards every 2 weeks to a target dose of 6 mg/day. Subjects in this group will be designated Group A. The remaining 30 subjects will also begin perampanel at a dose of 2 mg/day but will titrate upwards every 3 weeks to a target dose of 6 mg/day and will be designated Group B.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fycompa Titration Intervals and Effects on Retention Rate
• Actual Study Start Date: Apr 18, 2018
• Actual Primary Completion Date: Feb 24, 2021
• Actual Study Completion Date: Dec 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Fycompa 2 week titration intervals Perampanel oral tablet: 2mg by mouth every 24 hours for two weeks, then up-titrated by 2 mg every two weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control.	Drug: Perampanel Oral Tablet; Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.; Other Names: Fycompa
Experimental: Fycompa 3 week titration intervals Perampanel oral tablet: 2mg by mouth every 24 hours for three weeks, then up-titrated by 2 mg every three weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control.	Drug: Perampanel Oral Tablet; Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.; Other Names: Fycompa

Outcome Measures

Primary Outcome Measures

1. The Percentage of Subjects Completing 52 Weeks of Adjunctive Therapy During the Maintenance Phase [Retention Rate]. [Up to 52 weeks]

   Retention rate, which indirectly measures the therapeutic tolerance, will be measured at 52 weeks in each group.

Secondary Outcome Measures

1. Incidence of Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject or Observed by the Investigator [Safety and Tolerability]. [Up to 52 weeks]

   Adverse events experienced in each group will be tabulated and the total percentage of subjects reporting adverse events will be calculated.

2. Seizure Frequency Per 28 Days During Initial Titration and Final Maintenance Will be Calculated [Efficacy]. [Up to 52 weeks]

   Seizure frequency will be calculated per 28 days in each group during the initial titration phase and during the final maintenance phase.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Must provide written informed consent signed by the subject or legal guardian prior to entering the study in accordance with ICH and GCP guidelines.

2. Subject has a confirmed diagnosis of medically refractory epilepsy with or without secondary generalization for at least 12 months prior to visit 1.

3. Subjects currently being treated with 1 to 3 antiepileptic medications with or without VNS (does not count as an AED).

4. Subjects aged 18 to 75.

5. Subject's requiring an additional epilepsy medication due to either uncontrolled seizures and/or lack of tolerability with current epilepsy medications.

6. Can be safely treated, in the opinion of the investigator, with Fycompa.

7. Able and agrees to follow the specified titration schedule.

8. Subjects or a legal guardian who is able to communicate effectively with study personnel and considered reliable, able, willing and cooperative with regard to complying with protocol-defined requirements, including completion of the study diary.

Exclusion Criteria:

1. Any history of non-epileptic or psychogenic seizures.

2. Women who are currently pregnant, lactating or have plans to become pregnant in the immediate future.

3. Subjects with active suicidal ideation or behavior as evidenced by positive answers on the Columbia Suicide Severity Rating Scale (C-SSRS) or subject's with a history of suicidal ideation or attempt within 12 months.

4. Subjects with a suicidal attempt in the 12 months prior to Visit 1

5. Any clinically significant medical or psychiatric illness, psychological or behavioral problems, which in the opinion of the investigator would interfere with the subject's ability to participate in the study.

6. Subjects with severe hepatic impairment or severe renal impairment or on hemodialysis.

7. Any use of concomitant medication as listed in the drug insert, including medications known to be inducers of cytochrome P450 (CYP3A).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner University Medical Center Phoenix	Phoenix	Arizona	United States	85006

Sponsors and Collaborators

• University of Arizona
• Eisai Inc.

Investigators

• Principal Investigator: Norman C Wang, MD, Banner University Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 3, 2017

More Information

Publications

None provided.

• Responsible Party: Stephanie Marsh, Clinical Research Coordinator, University of Arizona
• ClinicalTrials.gov Identifier: NCT03457129
• Other Study ID Numbers: Fycompa Titration IIS
• First Posted: Mar 7, 2018
• Last Update Posted: Jun 7, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Stephanie Marsh, Clinical Research Coordinator, University of Arizona: Epilepsy; Epilepsy, partial onset; Epilepsy, generalized onset; Fycompa; perampanel
• Additional relevant MeSH terms: Epilepsy

Study Results

Participant Flow

Arm/Group Title	Fycompa 2 Week Titration Intervals	Fycompa 3 Week Titration Intervals
Arm/Group Description	Perampanel oral tablet: 2mg by mouth every 24 hours for two weeks, then up-titrated by 2 mg every two weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control. Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.	Perampanel oral tablet: 2mg by mouth every 24 hours for three weeks, then up-titrated by 2 mg every three weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control. Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.
Period Title: Overall Study
STARTED	10	10
COMPLETED	7	8
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Fycompa 2 Week Titration Intervals	Fycompa 3 Week Titration Intervals	Total
Arm/Group Description	Perampanel oral tablet: 2mg by mouth every 24 hours for two weeks, then up-titrated by 2 mg every two weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control. Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.	Perampanel oral tablet: 2mg by mouth every 24 hours for three weeks, then up-titrated by 2 mg every three weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control. Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.	Total of all reporting groups
Overall Participants	10	10	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	10 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33 (11)	43 (9)	37 (11)
Sex: Female, Male (Count of Participants)
Female	6 60%	4 40%	10 50%
Male	4 40%	6 60%	10 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 80%	10 100%	18 90%
More than one race	2 20%	0 0%	2 10%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Subjects Completing 52 Weeks of Adjunctive Therapy During the Maintenance Phase [Retention Rate].
Description	Retention rate, which indirectly measures the therapeutic tolerance, will be measured at 52 weeks in each group.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fycompa 2 Week Titration Intervals	Fycompa 3 Week Titration Intervals
Arm/Group Description	Perampanel oral tablet: 2mg by mouth every 24 hours for two weeks, then up-titrated by 2 mg every two weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control. Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.	Perampanel oral tablet: 2mg by mouth every 24 hours for three weeks, then up-titrated by 2 mg every three weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control. Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.
Measure Participants	7	8
Count of Participants [Participants]	2 20%	3 30%

2. Secondary Outcome

Title	Incidence of Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject or Observed by the Investigator [Safety and Tolerability].
Description	Adverse events experienced in each group will be tabulated and the total percentage of subjects reporting adverse events will be calculated.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Seizure Frequency Per 28 Days During Initial Titration and Final Maintenance Will be Calculated [Efficacy].
Description	Seizure frequency will be calculated per 28 days in each group during the initial titration phase and during the final maintenance phase.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 52 weeks
Arm/Group Title	Fycompa 2 Week Titration Intervals		Fycompa 3 Week Titration Intervals
Arm/Group Description	Perampanel oral tablet: 2mg by mouth every 24 hours for two weeks, then up-titrated by 2 mg every two weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control. Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.		Perampanel oral tablet: 2mg by mouth every 24 hours for three weeks, then up-titrated by 2 mg every three weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control. Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.
All Cause Mortality
	Fycompa 2 Week Titration Intervals		Fycompa 3 Week Titration Intervals
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Fycompa 2 Week Titration Intervals		Fycompa 3 Week Titration Intervals
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/10 (10%)
Nervous system disorders
Intractable Seizures	0/10 (0%)	0	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Fycompa 2 Week Titration Intervals		Fycompa 3 Week Titration Intervals
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		3/10 (30%)
Gastrointestinal disorders
Nausea	1/10 (10%)		1/10 (10%)
Infections and infestations
Head cold	1/10 (10%)	1	3/10 (30%)	5
Musculoskeletal and connective tissue disorders
Back pain	2/10 (20%)		1/10 (10%)
Joint pain	1/10 (10%)		0/10 (0%)
Nervous system disorders
Drowsiness	2/10 (20%)		1/10 (10%)
Dizziness	2/10 (20%)		3/10 (30%)
Numbness	0/10 (0%)		1/10 (10%)
Unsteadiness	0/10 (0%)		3/10 (30%)
Memory difficulty	0/10 (0%)		1/10 (10%)
Anxiety	1/10 (10%)		0/10 (0%)
Speech difficulty	1/10 (10%)		0/10 (0%)
Sleep difficulty	1/10 (10%)		1/10 (10%)
Psychiatric disorders
Anger	4/10 (40%)		3/10 (30%)
Renal and urinary disorders
Hydronephrosis	0/10 (0%)		1/10 (10%)
Reproductive system and breast disorders
Abnormal menses	1/10 (10%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Rash	1/10 (10%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.