Clinical trial NCT04520360: Bioavailability and Food Effect Study of 3 Types of Carisbamate
Official title: A Single-Center, Open-Label,Randomized, Crossover Study to Evaluate the Relative Bioavailability and Food Effect of a New Oral Suspension and Tablet Formulation of Carisbamate (YKP509) in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Carisbmate
Lennox-Gastaut syndrome (LGS)
Healthy Volunteers
Lead sponsor: SK Life Science, Inc.
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2020-08-20
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single center, open-label, randomized, 5-period, 10-sequence study designed to assess each treatment in all subjects enrolled in the study. The five treatments tested using a single oral administration will be: (1) Oral Suspension Type 1, 300 mg Oral Tablet, Oral Suspension Type 2 all under fasted conditions and (2) Oral Suspension Type 2, 300 mg Oral Tablet under fed conditions. Each dose is followed by at least a seven-day washout period. The sequence and period arrangement will be constructed based on the Williams design to ensure the study is balanced with respect to first-order carry-over effects.
Primary purpose: TREATMENT

Brief summary: This study is designed to examine the relative bioavailability of three carisbamate formulations (Oral Suspension Type 1, Oral Suspension Type 2, and a 300 mg Oral Tablet) and to assess the effect of food on the oral bioavailability of the Oral Suspension Type 2 and the 300 mg Oral Tablet.

Detailed description: This is a single center, open-label, randomized, 5-period, 10-sequence study designed to assess each treatment in 30 healthy subjects enrolled in the study. The five treatments tested using a single oral administration will be: (1) Oral Suspension Type 1, 300 mg Oral Tablet, Oral Suspension Type 2 all under fasted conditions and (2) Oral Suspension Type 2, 300 mg Oral Tablet under fed conditions. Each dose is followed by at least a seven-day washout period. The sequence and period arrangement will be constructed based on the Williams design to ensure the study is balanced with respect to first-order carry-over effects.

Eligibility criteria: Inclusion Criteria:

1. Male or female subjects of 18 to 50 years of age (inclusive)
2. Able to read, understand, sign, and date a written informed consent form (ICF) before study participation at screening
3. Agree to use 2 highly effective methods of contraception, including at least one barrier method
4. Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening
5. Judged to be in good health based on medical history, physical examination, and routine laboratory measurements (i.e., without clinically relevant pathology)
6. Normal electrocardiogram (ECG) (12-lead), arterial blood pressure, and heart rate within the normal standard range used by the study center or considered not clinically significant by the Investigator and in agreement with the Sponsor
7. Able to understand and comply with protocol requirements and instructions and likely to complete the study as planned
8. A female study subject of childbearing potential must agree to use one of the accepted contraceptive method from Screening, during the study, and for at least 90 days after the last dose of the study medication. Hormonal contraceptives alone will not be considered an adequate method of contraception.
9. A female study subject must agree not to donate eggs (oocytes) during the study and for at least 90 days after the last dose of the study medication
10. Females of non-childbearing potential who have undergone a sterilization procedure at least 6 months prior to dosing with official documentation (e.g., hysteroscopic sterilization, bilateral tubal ligation or bilateral salpingectomy, hysterectomy, or bilateral oophorectomy) or become postmenopausal with amenorrhea for at least 1 year prior to dosing and have follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status as per Principal Investigator's judgment
11. Subjects are able and willing to consume a high-fat meal within a 30 minute timeframe

Exclusion Criteria:

1. History of any illness or condition that, in the opinion of the Investigator, might confound the results of the study or pose additional risks in administering study drug to the subjects

1. Smokers (subjects who have smoked within 6 months prior to screening or those subjects with a positive result from the smoking screening assay)
2. Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with pharmacokinetics of the study drug (except appendectomy and simple hernia repair).
3. Regular treatment with prescription medications. Subjects should have ended any prescription medications at least 14 days before the first dosing of the study drug. Potential subjects should only stop any prescribed medication at the direction of a physician or qualified medical professional.
4. Regular treatment with nonprescription medications. Subjects should have ended any nonprescription medications at least 14 days before the first dosing of the study drug. Potential subjects should consult with a physician or qualified medical professional before stopping any regular treatment with nonprescription medication.
5. Consumption of herbal medications, dietary supplements, and specific fruit products. Subjects should have stopped consumption of herbal medications or dietary supplements (e.g., St. John's Wort, ginkgo biloba, and garlic supplements), vitamins, and grapefruit or grapefruit juice, or Seville oranges at least 14 days before the first dosing of study drug.
6. History of drug or alcohol abuse or addiction within 2 years before the start of study drug dosing, or a positive test results for alcohol or drugs of abuse, such as amphetamine, barbiturate, benzodiazepine, cocaine, methadone, opiates, oxycodone, phencyclidine, propoxyphene, cannabinoid (THC), MDMA (Ecstasy), methaqualone, and tricyclic antidepressant (TCA).
7. Regular consumption of more than 2 units of alcoholic beverages per day or more than 14 units per week (1 unit of alcohol equals 1 pint \[473 mL\] of beer or lager, 1 glass \[125 mL\] of wine, 25 mL shot of 40% spirit) before screening. Subjects may not consume any alcohol from 72 hours before the first dosing of study drug through the completion of the last PK sampling.
8. Consumption of an average of more than 5 servings per day of coffee, tea, chocolate, cola, or other caffeinated or methyl xanthine beverages before screening. Subjects may not consume any tea, coffee, chocolate, and other foods and beverages containing caffeine and other methyl xanthine derivatives from 48 hours prior to dosing until the collection of the last PK sample.
9. Participation in a clinical study involving administration of either an investigational or a marketed drug within 2 months or 7 half-lives (whichever is longer) before screening.
10. Blood donation or a significant loss of blood within 60 days of the start of study drug dosing or donation of more than 1 unit of plasma within 7 days before screening.
11. Positive result at screening for any of the following infectious disease tests: hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), human immunodeficiency virus antigen and antibody (HIV-1/2 Ag/Ab)
12. Illness within 5 days before the start of study drug dosing ("illness" is defined as an acute \[serious or non-serious\] condition \[e.g., the flu or the common cold\])
13. History of any known relevant allergy/hypersensitivity (including allergy to the trial medication or its excipients)
14. Women who are pregnant or breastfeeding
15. Subject who is judged not eligible for study participation by Investigator
16. Subject is at imminent risk of suicide (positive response to question 4 or 5 on the C-SSRS) or had a suicide attempt within 6 months prior to the Screening visit

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 35 days
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: PRA Health Sciences- Salt Lake City
state: Utah
Study officials:
affiliation: SK Life Science, Inc.
name: Ry R Forseth, Ph.D.
role: STUDY_CHAIR
References: