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Drug Trials Snapshots: XCOPRI

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to XCOPRI Prescribing Information for complete information.

XCOPRI (cenobamate)
ex koe' pree
SK Life Science, Inc.
Approval date: November 21, 2019


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

XCOPRI is a drug for the treatment of specific type of seizures called partial-onset seizures in adult patients.

Partial-onset seizures occur when clusters of nerve cells (neurons) undergo uncontrolled activation in a limited area of the brain.

How is this drug used?

XCOPRI is a tablet drug that is taken once daily by mouth. An initial low dose may be increased every two weeks according to a special schedule.

What are the benefits of this drug?

Patients taking XCOPRI had less frequent seizures than patients taking placebo.

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results for the clinical trials.

Table 1. Percent Change from Baseline in Seizure Frequency per 28 Days in the Treatment Period

  N Median Percent Change from Baseline in Seizure Frequency per 28 Days (%)ƚ p-value (Compared to Placebo)
Trial 1
Placebo 108 -21.5 --
200 mg/day 113 -55.6 < 0.0001*
Trial 2
Placebo 106 -24.3 --
100 mg/day 108 -36.3   0.006*
200 mg/day 109 -55.2 < 0.001*
400 mg/day 111 -55.3 < 0.001*

ƚ A negative percent change from baseline in seizure frequency indicates reduction in seizure frequency from baseline.
* Statistically significant compared to placebo

XCOPRI Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: XCOPRI worked similarly in men and women.
  • Race: The majority of patients in the clinical trial were White. Differences in how well XCOPRI worked among different races could not be determined.
  • Age: The majority of patients in the clinical trial were younger than 65 years of age. Differences in how well XCOPRI worked between patients below and above 65 years of age could not be determined.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The table below summarizes efficacy results by subgroup. Age differences were not explored because few patients were older than 65 years.

Table 2. Subgroup Analyses of Primary End-Point by Sex

  Trial 1
(ITT populationa)
Trial 2
(mITT populationa)
Seizure frequency per 28 days XCOPRI
200 mg
(N = 113)
Placebo (N = 108) XCOPRI
400 mg
(N = 111)
XCOPRI
200 mg
(N = 109)
XCOPRI
100 mg
(N = 108)
Placebo (N = 106)
Women
n 58 50 59 55 51 50
Median at baseline 8.2 8.1 8.0 16.0 10.0 9.3
Median of the treatment period 4.0 9.8 4.2 6.7 6.2 8.9
Median percent change from baseline -58.3 -17.5 -53.3 -55.6 -44.4 -21.3
Men
n 55 58 52 54 57 56
Median at baseline 6.5 5.3 9.8 9.3 8.0 7.8
Median of the treatment period 3.7 3.8 3.3 5.2 5.2 6.1
Median percent change from baseline -44.7 -30.4 -58.9 -53.5 -32.2 -25.9

Table 3. Subgroup Analyses of Primary End-Point by Race

  Trial 1
(ITT populationa)
Trial 2
(mITT populationa)
Seizure frequency per 28 days XCOPRI
200 mg
(N = 113)
Placebo
(N = 108)
XCOPRI
400 mg
(N = 111)
XCOPRI
200 mg
(N = 109)
XCOPRI
100 mg
(N = 108)
Placebo
(N = 106)
Non-White
N 56 51 15 16 19 15
Median at baseline 6.5 5.0 8.5 10.0 7.0 8.7
Median of the treatment period 3.3 4.9 4.2 4.1 6.1 6.1
Median percent change from baseline -58.3 -18.4 -56.0 -61.3 -18.1 -24.4
White
n 57 57 96 93 89 91
Median at baseline 8.5 7.0 9.0 13.0 10.0 8.2
Median of the treatment period 4.0 5.3 3.7 5.8 5.8 7.1
Median percent change from baseline -44.7 -23.5 -55.0 -52.5 -39.5 -23.4

aThe primary efficacy analysis population was called the ITT population in Trial 1 and the mITT population in Trial 2

FDA Statistical Review

What are the possible side effects?

XCOPRI may cause serious side effects including life-threatening allergic reactions (called Drug Reaction with Eosinophilia and Systemic Symptoms or DRESS), thoughts about suicide or dying, heart rhythm problems (because of a shortened QT interval), and drowsiness which may impair driving ability.

The most common side effects of XCOPRI are drowsiness, dizziness, feeling tired, double vision, and headache.

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes adverse reactions in pooled placebo-controlled adjunctive therapy trials in patients with partial-onset seizures.

Table 4. Adverse Reactions in Pooled Placebo-Controlled Adjunctive Therapy Trials in Patients with Partial-Onset Seizures with XCOPRI Frequency in Any Treatment Arm Greater Than 1% Over Placebo

  Adverse Reaction XCOPRI Placebo
100mg 200mg 400mg
n = 108
%
n= 223
%
n=111
%
n=216
%
Cardiac Disorders
Palpitations 0 0 2 0
Ear and Labyrinth Disorders
Vertigo 1 1 6 1
Eye Disorders
Diplopia 6 7 15 2
Vision Blurred 2 2 4 0
Gastrointestinal Disorders
Nausea 6 6 9 3
Constipation 2 4 8 0
Diarrhea 1 3 5 0
Vomiting 2 4 5 0
Dry Mouth 1 1 3 0
Abdominal Pain 2 2 1 0
Dyspepsia 2 2 0 0
Infections and Infestations
Nasopharyngitis 2 4 5 3
Pharyngitis 1 2 0 0
Urinary Tract Infection 2 5 0 2
Injury, Poisoning and Procedural Complications
Head Injury 1 0 2 0
Investigations
Alanine Aminotransferase Increased 1 1 4 0
Aspartate Aminotransferase Increased 1 1 3 0
Weight Decreased 2 0 1 0
Metabolism and Nutrition Disorders
Decreased Appetite 3 1 5 1
Musculoskeletal and Connective Tissue Disorders
Back Pain 4 2 5 3
Musculoskeletal Chest Pain 2 1 0 0
Nervous System Disorders
Somnolence 19 22 37 11
Dizziness 18 22 33 15

XCOPRI Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The occurrence of side effects was similar in men and women
  • Race: The occurrence of side effects was similar among tested race groups.
  • Age: The majority of patients in the clinical trial were younger than 65 years of age. Differences in side effects between patients below and above 65 years of age could not be determined.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The figures below depict adverse events by sex and race subgroup. Age differences were not explored because few patients were older than 65 years.

Figure 4. Subgroup Analysis of Nervous System SOC Events in Pooled Trials by Sex

Table summarizes adverse reactions by subgroups.

Adapted from FDA Clinical Review

Figure 5. Subgroup Analysis of Nervous System SOC Events in Pooled Trials by Race

Table summarizes adverse reactions population by subgroups.

Adapted from FDA Clinical Review

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved XCOPRI based primarily on evidence from two clinical trials (Trial 1/NCT01866111 and Trial2/NCT01397968) of 655 patients with partial-onset seizures.

The trials were conducted at 147 sites in the USA, Europe, Asia, Australia, Israel, and South Africa.

The figure below summarizes how many men and women were in the clinical trials.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trial. In total, 245 women (55%) and 203 men (45%) participated in the clinical trial.

Clinical Trial Data

Figure 2 summarizes the percentage of patients by race in the clinical trials.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the clinical trial. In total, 429 White (96%), 15 Asian (3%) and Black or African American 2 (<1%) and Nativ Hawaiian or Pacific Islander 2 (<1%)

Clinical Trial Data

Figure 3 summarizes the percentage of patients by age enrolled in the clinical trials.

Figure 3. Baseline Demographics by Age

Pie charts summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total,  212 (47%) were less than 65 years, and 236 (53%) of patients were 65 years and older.

Clinical Trial Data

Who participated in the trials?

The table below summarizes demographics of patients in the clinical trials.

Table 6. Baseline Demographics of Patients in the Clinical Trials (efficacy population)

Demographic Characteristic Trial 1
N=221
Trial 2
N=434
Total
N=655
Sex, n (%)
Men 113 (51.1) 219 (50.5) 332 (50.7)
Women 108 (48.9) 215 (49.5) 323 (49.3)
Race, n (%)
White 114 (51.6) 369 (85) 483 (73.7)
Black or African American 5 (2.3) 12 (2.8) 17 (2.6)
Asian 94 (42.5) 41 (9.4) 135 (20.6)
Other 3 (1.4) 12 (2.8) 15 (2.3)
Unknown 5 (2.3) 0 5 (0.8)
Age
Median (Min, Max) 37 (18,61) 38 (19,70) 38 (18,70)
Age Group, n (%)
<65 years 221 (100) 424 (97.7) 645 (98.5)
≥65 years 0 10 (2.3) 10 (1.5)
Ethnicity, n (%)
Hispanic or Latino 7 (3.2) 36 (8.3) 43 (6.5)
Not Hispanic or Latino 205 (92.8) 398 (91.7) 603 (92.1)
Not reported 9 (4.1) 0 9 (1.4)
Geographic Region, n (%)
USA 86 (38.9) 109 (25.1) 195 (29.3)
Europe 43 (19.5) 250 (57.6) 293 (44.7)
Asia 41 (18.5) 39 (9) 80 (12.2)
*Rest of the World 51 (23.1) 36 (8.3) 87 (13.3)

* Australia, Israel and South Africa

Clinical Trial Data

How were the trials designed?

The benefit and side effects of XCOPRI were evaluated in two clinical trials of patients with partial-onset seizures who were not adequately controlled on their current therapy. Both trials had an 8-week period to assess baseline seizure frequency while patients were taking their usual treatments for seizures. After 8 weeks and in addition to their usual treatments for seizures, patients received either XCOPRI tablets at various doses or placebo tablets for 12 weeks. Neither the patients nor the health care providers knew which new treatment was being given until after the trial was completed.

The benefit of XCOPRI was evaluated by measuring the difference from baseline in number of seizures per 28 days of treatment and comparing it to the placebo.

Patients from both trials who completed the treatment with either XCOPRI or placebo were eligible to continue taking XCOPRI in order to collect long-term safety data.

How were the trials designed?

The safety and efficacy of XCOPRI were primarily established in 2 randomized, double-blind, placebo-controlled, multicenter trials. Randomized patients had to have partial-onset seizures that were not adequately controlled with 1 to 3 concomitant antiepileptic drugs.

The trials had an 8-week baseline period followed by a 12-week treatment period. Trial 1 compared a dose of XCOPRI 200 mg/day with placebo. Trial 2 compared doses of XCOPRI 100 mg/day, 200 mg/day, and 400 mg/day with placebo.

The efficacy outcome measure in both trials was the percent reduction from baseline in seizure frequency per 28 days during the treatment period.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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