Study to Evaluate Bioavailability of a Single 12 mg Dose of Perampanel for Three Intravenous Infusion Durations Relative to a Single 12 mg Perampanel Oral Tablet in Healthy Subjects

NCT03376997 | Completed Phase 1 FDA Drug

• 1 other identifier: E2007-A001-050
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be conducted to evaluate the bioavailability of a single 12 milligram (mg) dose of perampanel intravenous infusions of different durations relative to a single 12 mg dose of perampanel oral tablet in healthy participants.

Conditions

Healthy Participants

Keywords

Bioavailability; Perampanel

Outcome Measures

Primary Outcomes (3)

• Mean maximum observed concentration (Cmax) postdose of perampanel

  Cmax is the maximum plasma concentration of a drug after administration. Dosing will occur on Day 1 of Treatment Period 1 and Day 43 of Treatment Period 2.

  predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (Day [D]1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start

• Mean value for area under the concentration versus time curve from time 0 to time of last measurable concentration (AUC[0-t]) postdose of perampanel

  AUC is a measure of actual body exposure to drug after administration of the drug. Dosing will occur on Day 1 of Treatment Period 1 and Day 43 of Treatment Period 2.

  predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start

• Mean value for AUC versus time curve from time 0 to infinity (AUC[0-inf]) postdose of perampanel

  AUC is a measure of actual body exposure to drug after administration of the drug. Dosing will occur on Day 1 of Treatment Period 1 and Day 43 of Treatment Period 2.

  predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start

Secondary Outcomes (11)

• Mean value for AUC versus time curve from time 0 to 72 hours (AUC[0-72h]) postdose of perampanel

  predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start

• Mean time to reach maximum concentration (tmax) postdose of perampanel

  predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start

• Mean terminal phase half-life (t1/2) postdose of perampanel

  predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start

• Mean total clearance (CL) post intravenous (IV) infusion of perampanel

  predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start

• Mean volume of distribution (Vd) post IV infusion of perampanel

  predose; 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 (D1 and D43); 24 and 36 (D2 and D44); 48 (D3 and D45); 72 (D4 and D46); 120 (D6 and D48); 168 (D8 and D50); 336 (D15 and D57); and 504 (D22 and D64) hours after dosing start

Study Arms (3)

Perampanel: 30-minute IV infusion and 12 mg oral tablet

EXPERIMENTAL

Participants will be randomized on Day 1 of Treatment Period 1 to receive either a single 12 milligram (mg) dose of perampanel intravenous (IV) infusion (30-minute duration) or a single 12 mg oral tablet after an overnight fast. Participants will then receive the alternative treatment on Day 43 of Treatment Period 2. Drug administration will be separated by a washout of at least 6 weeks between the 2 treatment periods.

Drug: Perampanel

Perampanel: 60-minute IV infusion and 12 mg oral tablet

EXPERIMENTAL

Participants will be randomized on Day 1 of Treatment Period 1 to receive either a single 12 mg dose of perampanel IV infusion (60-minute duration) or a single 12 mg oral tablet after an overnight fast. Participants will then receive the alternative treatment on Day 43 of Treatment Period 2. Drug administration will be separated by a washout of at least 6 weeks between the 2 treatment periods.

Drug: Perampanel

Perampanel: 90-minute IV infusion and 12 mg oral tablet

EXPERIMENTAL

Participants will be randomized on Day 1 of Treatment Period 1 to receive either a single 12 mg dose of perampanel IV infusion (90-minute duration) or a single 12 mg oral tablet after an overnight fast. Participants will then receive the alternative treatment on Day 43 of Treatment Period 2. Drug administration will be separated by a washout of at least 6 weeks between the 2 treatment periods.

Drug: Perampanel

Interventions

Perampanel DRUG

IV infusion

Also known as: E2007

Perampanel: 30-minute IV infusion and 12 mg oral tablet; Perampanel: 60-minute IV infusion and 12 mg oral tablet; Perampanel: 90-minute IV infusion and 12 mg oral tablet

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Non-smoking, male or female, between 20 and 55 years of age (inclusive) at the time of informed consent
• Body mass index (BMI) of 18 to 32 kilograms per meters squared (kg/m\^2) (inclusive) at Screening
• For Japanese participants:
• i. Born in Japan to Japanese parents and grandparents of Japanese descent; ii. Have been living outside Japan for less than 5 years; and iii. Lifestyle, including diet, has not changed significantly since leaving Japan
• Provide written informed consent
• Willing and able to comply with all aspects of the protocol

You may not qualify if:

• Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[ß-hCG\]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
• Females of childbearing potential who:
• i. Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
• total abstinence (if it is their preferred and usual lifestyle);
• an intrauterine device or intrauterine hormone-releasing system (IUS);
• a contraceptive implant;
• an oral contraceptive (with additional barrier method). Participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation; or
• have a vasectomized partner with confirmed azoospermia ii. Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
• Evidence of disease that may influence the outcome of the study within 4 weeks of dosing, eg, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, cardiovascular system, or participants who have a congenital abnormality in metabolism
• Any history of gastrointestinal surgery that may affect pharmacokinetics (PK) profiles of perampanel, eg, hepatectomy, nephrectomy, digestive organ resection or any gastrointestinal procedure for the purpose of weight loss (including Lapband™), which would slow gastric emptying
• Any clinically abnormal symptom or organ impairment found by medical history at Screening, and physical examinations, vital signs, electrocardiogram (ECG) finding, or laboratory test results that require medical treatment at Screening or Baseline. A single repeat test for an abnormal vital sign and/or laboratory value is permitted, at the discretion of the Investigator.
• A prolonged QT/QTc interval (QTc \>450 milliseconds \[msec\]) as demonstrated upon repeat ECG at Screening or Baseline
• Heart rate \<50 or \>100 beats per minute at Screening or Baseline
• History of ischemic heart disease (eg, acute coronary syndromes, stable angina), syncope or cardiac arrhythmias

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

Related Publications (1)

• Hussein Z, Majid O, Boyd P, Aluri J, Ngo LY, Reyderman L. Intravenous Perampanel as an Interchangeable Alternative to Oral Perampanel: A Randomized, Crossover, Phase I Pharmacokinetic and Safety Study. Clin Pharmacol Drug Dev. 2022 Jul;11(7):878-888. doi: 10.1002/cpdd.1107. Epub 2022 May 20.

  PMID: 35596529 DERIVED

MeSH Terms

Interventions

perampanel

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 19, 2017
• Study Start: November 8, 2017
• Primary Completion: February 16, 2018
• Study Completion: February 16, 2018
• Last Updated: September 7, 2018

Record last verified: 2017-12

Locations

US (1)