HealthyPhase 1NCT03234699
Assess the Influence of Cenobamate on the PK of Cytochrome P450 (CYP) Probe Drugs As a Means of Predicting Drug-drug Interactions
A Phase 1 study testing Cenobamate, midazolam and Warfarin Pill in people with Healthy, run by SK Life Science, Inc. at 1 site in United States.
Trial summary
This study is aimed to investigate the influence of cenobamate on the activity of CYP3A4/5, CYP2B6, CYP2C19, and CYP2C9 by using drugs recommended by both the FDA and EMA as in vivo probes. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Cenobamate, midazolam and Warfarin Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Feb 2017to 31 Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female subjects between 18 to 50 years of age inclusive
- Subject is willing and able to provide informed consent
- Body mass index (BMI) within 19.0 kg/m2 and 29.9 kg/m2, inclusive, at screening
- Subject is a non- or ex-smoker and has not used any nicotine containing products within 6 months prior to screening
- Subjects who are considered generally healthy upon completion of medical history, physical examination, vital signs, screening laboratory results and screening ECG in the opinion of the Investigator
- Subjects who are willing and able to comply with the dosing/visit schedule, laboratory tests, pharmacokinetic sampling schedule, and other study procedures
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- A female study subject must meet one of the following criteria:
- If of childbearing potential - agrees to use one of the accepted contraceptive regimens from screening, during the study and for at least 30 days after the last dose of the study medication. Hormonal contraceptives alone will not be considered an adequate method of contraception. An acceptable method of contraception includes one of the following:
- Diaphragm and spermicide
- Condom with spermicide
- Sponge and spermicide
- Intrauterine device (with or without hormones; placement at least 3 months prior to Screening) in combination with a barrier method
- Oral contraceptives, Depo-Provera, Norplant, Patch or intrauterine progesterone contraceptive for at least 90 days prior to screening in combination with a barrier method.
- Vasectomized partner (6 months minimum since vasectomy)
- Complete abstinence from heterosexual intercourse. However, if the subject becomes sexually active, 1 of the above methods must be utilized.
- If a female of non-childbearing potential - should be surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation at least 6 months prior to Screening) or in a menopausal state (at least 1 year without menses), as confirmed by FSH levels (post menopausal must be confirmed by the subject having a serum follicle stimulating hormone greater than 40mIU/ml at screening)
- A female study subject must agree not to donate eggs during the study and for at least 30 days after the last dose of the study medication
- A male study subject must agree to use one of the accepted contraceptive regimens during the study and for at least 90 days after the last dose of the study medications;
- Abstinence from heterosexual intercourse. However, if the subject becomes sexually active, 1 of the below methods must be utilized
- Female partner with hormonal contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch) in combination with a barrier method
- Female partner with intrauterine device (with or without hormones) in combination with a barrier method
- Female partner with condom with spermicide used by male study subject
- Female partner of non-childbearing potential
- Female partner with diaphragm with spermicide
- Female partner with sponge and spermicide
- Male sterilization with absence of sperm in the post vasectomy ejaculate for ≥ 6 months
- A male study subject must agree not to donate sperm during the study and for at least 90 days after the last dose of the study medication
Who cannot join
- Females who are breastfeeding
- Inadequate venous access
- History of any drug related hypersensitivity reactions as well as severe hypersensitivity reactions (like angioedema), or DRESS syndrome to any drugs in the opinion of the Investigator
- History of 1st degree relative having a serious cutaneous adverse reaction
- Current clinically significant rash
- Clinically significant history or evidence of gastrointestinal, hepatic, renal, endocrine, pulmonary, neurological, psychiatric, cardiovascular, hematologic, dermatologic, immunologic disease or any other condition known to interfere with the absorption, distribution, metabolism or elimination of drugs that in the opinion of the Investigator would jeopardize the safety of the subject or impact validity of study results
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- History of hepatic impairment, cholecystectomy, renal impairment or any other condition known to interfere with the absorption, distribution, metabolism or elimination of orally administered drug
- Presence of observed abnormality (evidenced from physical examination, ECG, vital signs, or laboratory evaluation) that would be clinically significant in the opinion of the Investigator
- Current evidence or history of suicidal tendency, seizures, state of confusion or any other clinically relevant psychiatric disease.
- 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
- History of regular alcohol consumption exceeding 7 drinks per week for females and 14 drinks per week for males within 6 months prior to screening
- Has current or recent history (within the past year) of alcohol or drug abuse or dependence
- Any clinically significant illness in the previous 30 days prior to screening
- Use of any enzyme-modifying drugs, including strong inhibitors of CYP enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort) in the previous 30 days prior to Day 1 of this study
- Use of all drugs associated with DRESS syndrome such as phenobarbital, carbamazepine, phenytoin, lamotrigine, minocycline, sulfonamides, allopurinol, modafinil, dapsone, ziprasidone, vancomycin and olanzapine in the previous 6 months prior to Day 1 of this study
- Clinically-relevant, unusual dietary habits (e.g., vegan, Atkins), dietary restrictions, and/or food allergies
- Positive urine screen for alcohol and/or drugs of abuse at screening and at each admission
- Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Antibody (HCVAb) at screening
- Has been administered any investigational drug 30 days (or 6 times its terminal half-live) prior to Day 1 of this study
- Females with a positive pregnancy test at screening, regardless of child-bearing potential prior to Day 1 of this study
- Blood donation (excluding plasma donation) of approximately 500 mL within 56 days prior to screening
- Subject is unlikely to comply with the study protocol or, in the opinion of the Investigator, would not be a suitable candidate for participation in the trial
- Anyone who has previously been exposed to cenobamate (prior to participation in this study)
Trial locations and contacts
1 site in 1 country.
United States1 site
Vince and Associates Clinical Research, Inc.
Overland Park, Kansas, 66212
About this study
Official title: The Effect of Multiple Doses of Cenobamate (YKP3089) on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (midazolam, Warfarin, Omeprazole and Bupropion) Administered Orally in an Open-label, One-sequence Study in Healthy Subjects
This study is aimed to investigate the influence of cenobamate on the activity of CYP3A4/5, CYP2B6, CYP2C19, and CYP2C9 by using drugs recommended by both the FDA and EMA as in vivo probes. In order to avoid a potential pharmacokinetic interaction between the probes, midazolam (CYP3A), warfarin (CYP2C9), and omeprazole (CYP2C19) will be administered together as a validated cocktail and separately from bupropion (CYP2B6) using an adequate washout time period between the 2 assessments.
The starting daily dose of cenobamate will be 12.5 mg, which will be administered for 2 weeks. Then, daily cenobamate doses will be increased every 2 weeks to 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg. The CYP probes will be tested before cenobamate administration, at steady state at 100mg/day of cenobamate for midazolam only and finally at steady state at 200mg/day of cenobamate for all CYP probes.
The results of this DDI study will provide a basis to make appropriate dose recommendation for a safe use of concomitant drugs with cenobamate using these isoenzymes in their metabolic pathway.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CenobamateDrug
12.5 mg q.d.(Days 13-26), 25 mg q.d. (Days 27-40), 50 mg q.d. (Days 41-54), 100 mg q.d. (Days 55-70), 150 mg q.d. (Days 71-84), 200 mg q.d. (Days 85-110)
midazolamDrug
2 mg midazolam syrup (Days 7, 69, 105)
Warfarin PillDrug
5 mg (Days 7 and 105)
Omeprazole PillDrug
20 mg (Days 7 and 105)
Bupropion PillDrug
150 mg (Days 1 and 99)
| Study group | Role | What they receive |
|---|---|---|
| Single Group | Experimental | Not described Receives: Drug: Cenobamate; Drug: midazolam; Drug: Warfarin Pill; Drug: Omeprazole Pill; Drug: Bupropion Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic parameters AUC
Will be determined for S- and R-bupropion, total bupropion, midazolam, S-warfarin and R-warfarin, and omeprazole when administered with and without cenobamate at steady state
Measured: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Pharmacokinetic parameters Cmax
Will be determined for S- and R-bupropion, total bupropion, midazolam, S-warfarin and R-warfarin, and omeprazole when administered with and without cenobamate at steady state
Measured: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Secondary outcomes (4)
Pharmacokinetic parameters AUC
Will be determined for probe drug metabolites (S,S-hydroxybupropion and R,R-hydroxybupropion, threohydrobupropion, 1-hydroxymidazolam, and 5-OH omeprazole)
Measured: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Pharmacokinetic parameters Cmax
Will be determined for probe drug metabolites (S,S-hydroxybupropion and R,R-hydroxybupropion, threohydrobupropion, 1-hydroxymidazolam, and 5-OH omeprazole)
Measured: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Pharmacokinetic parameters AUC (to infinity)
Will be determined for probe drug metabolites (S,S-hydroxybupropion and R,R-hydroxybupropion, threohydrobupropion, 1-hydroxymidazolam, and 5-OH omeprazole)
Measured: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Pharmacokinetic parameter RAUC (ratio of metabolite to parent)
Will be determined for 5-OH omeprazole/omeprazole, 1-OH midazolam/midazolam, S,S-OH-bupropion/S-bupropion, R,R-OH-bupropion/R-bupropion, total OH-bupropion/total bupropion, threohydrobupropion/R-bupropion
Measured: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start22 Feb 2017
- Primary completion3 Jul 2017
- Study completion31 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- SK Life Science, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03234699
- Sponsor's protocol ID
- YKP3089C026
- Status last verified
- Sep 2024
- First submitted
- 17 Apr 2017
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Multiple Doses of Cenobamate (YKP3089) on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (midazolam, Warfarin, Omeprazole and Bupropion) Administered Orally in an Open-label, One-sequence Study in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03234699
- Acronym / sponsor ID
- YKP3089C026
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- SK Life Science, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Feb 2017 (actual)
- Primary completion
- 3 Jul 2017 (actual)
- Study completion
- 31 Jul 2017 (actual)
- First posted
- 31 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is aimed to investigate the influence of cenobamate on the activity of CYP3A4/5, CYP2B6, CYP2C19, and CYP2C9 by using drugs recommended by both the FDA and EMA as in vivo probes. In order to avoid a potential pharmacokinetic interaction between the probes, midazolam (CYP3A), warfarin (CYP2C9), and omeprazole (CYP2C19) will be administered together as a validated cocktail and separately from bupropion (CYP2B6) using an adequate washout time period between the 2 assessments.
The starting daily dose of cenobamate will be 12.5 mg, which will be administered for 2 weeks. Then, daily cenobamate doses will be increased every 2 weeks to 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg. The CYP probes will be tested before cenobamate administration, at steady state at 100mg/day of cenobamate for midazolam only and finally at steady state at 200mg/day of cenobamate for all CYP probes.
The results of this DDI study will provide a basis to make appropriate dose recommendation for a safe use of concomitant drugs with cenobamate using these isoenzymes in their metabolic pathway.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Group | Experimental | Drug: Cenobamate, Drug: midazolam, Drug: Warfarin Pill, Drug: Omeprazole Pill, Drug: Bupropion Pill |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (27 listed)
- Male or female subjects between 18 to 50 years of age inclusive
- Subject is willing and able to provide informed consent
- Body mass index (BMI) within 19.0 kg/m2 and 29.9 kg/m2, inclusive, at screening
- Subject is a non- or ex-smoker and has not used any nicotine containing products within 6 months prior to screening
- Subjects who are considered generally healthy upon completion of medical history, physical examination, vital signs, screening laboratory results and screening ECG in the opinion of the Investigator
Key exclusion criteria (23 listed)
- Females who are breastfeeding
- Inadequate venous access
- History of any drug related hypersensitivity reactions as well as severe hypersensitivity reactions (like angioedema), or DRESS syndrome to any drugs in the opinion of the Investigator
- History of 1st degree relative having a serious cutaneous adverse reaction
- Current clinically significant rash
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cenobamate12.5 mg q.d.(Days 13-26), 25 mg q.d. (Days 27-40), 50 mg q.d. (Days 41-54), 100 mg q.d. (Days 55-70), 150 mg q.d. (Days 71-84), 200 mg q.d. (Days 85-110) | Drug | Single Group |
| midazolam2 mg midazolam syrup (Days 7, 69, 105) | Drug | Single Group |
| Warfarin Pill5 mg (Days 7 and 105) | Drug | Single Group |
| Omeprazole Pill20 mg (Days 7 and 105) | Drug | Single Group |
| Bupropion Pill150 mg (Days 1 and 99) | Drug | Single Group |
Primary outcome
Pharmacokinetic parameters AUC
Time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Will be determined for S- and R-bupropion, total bupropion, midazolam, S-warfarin and R-warfarin, and omeprazole when administered with and without cenobamate at steady state
Pharmacokinetic parameters Cmax
Time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Will be determined for S- and R-bupropion, total bupropion, midazolam, S-warfarin and R-warfarin, and omeprazole when administered with and without cenobamate at steady state
4 secondary outcomes
Pharmacokinetic parameters AUC
Time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Pharmacokinetic parameters Cmax
Time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Pharmacokinetic parameters AUC (to infinity)
Time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Pharmacokinetic parameter RAUC (ratio of metabolite to parent)
Time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cenobamate, midazolam and Warfarin Pill in people with Healthy, run by SK Life Science, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic parameters AUC (time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.