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The primary objective of this study is to evaluate the effect of multiple doses of the UGT inhibitor valproic acid on the single-dose pharmacokinetics of BIIB074. The secondary objectives of this study are to evaluate the safety and tolerability of BIIB074 when administered alone and when coadministered with the UGT inhibitor valproic acid and to evaluate the effect of the UGT inhibitor valproic acid on the PK of the M13, M14, and M16 metabolites of BIIB074.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BIIB074 150 mg and Valproic Acid 500 mg | Experimental | Participants will receive BIIB074 in tablet form in 150 mg doses. BIIB074 will be taken once daily (QD) on Days 1-16 after an 8-hour fast. Valproic Acid will be given in capsule form in 500 mg doses on prescription (TID) every 8 hours on Days 8-22. The morning dose on Day 16 will be coadministered with BIIB074 following an 8-hour fast. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BIIB074 | Drug | Administered as specified in the treatment arm |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Concentration (Cmax) of BIIB074 | Day 1 through Day 8, Day 16 through Day 23 | |
| Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB074 | Day 1 through Day 8, Day 16 through Day 23 | |
| Area Under the Concentration-Time Curve from Time Zero to Time of the Last Measurable Concentration (AUClast) of BIIB074 | Day 1 through Day 8, Day 16 through Day 23 | |
| Time to Reach Maximum Observed Concentration (Tmax) for BIIB074 | Day 1 through Day 8, Day 16 through Day 23 | |
| Time of Last Measured Serum Concentration (Tlast) of BIIB074 | Day 1 through Day 8, Day 16 through Day 23 | |
| Elimination Half-Life (T 1/2) of BIIB074 | Day 1 through Day 8, Day 16 through Day 23 | |
| Apparent Clearance (CL/F) of BIIB074 | Day 1 through Day 8, Day 16 through Day 23 | |
| Apparent Volume of Distribution (V/F) of BIIB074 | Day 1 through Day 8, Day 16 through Day 23 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. | Up to Day 32 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Biogen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Dallas | Texas | 75247 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36045316 | Derived | Zhao Y, Kotecha M, Finnigan H, Serenko M, Naik H. Evaluation of the Effect of Uridine Diphosphate-Glucuronosyltransferases (UGT) Inhibition by Valproic Acid on Vixotrigine Pharmacokinetics in Healthy Volunteers. Clin Drug Investig. 2022 Oct;42(10):829-837. doi: 10.1007/s40261-022-01194-y. Epub 2022 Aug 31. |
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| ID | Term |
|---|---|
| C000592131 | vixotrigine |
| D014635 | Valproic Acid |
| ID | Term |
|---|---|
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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| Valproic Acid |
| Drug |
Administered as specified in the treatment arm |
|
|
| Number of Participants with Abnormal Change from Baseline of Electrocardiogram (ECG) up to Day 23 |
| Day 1, 3, 8, 13, 16, 18, 23 |
| Number of Participants with Abnormal Change from Baseline of Clinical Laboratory Parameters up to Day 23 | Day 3, 8, 13, 16, 18, 23 |
| Number of Participants with Abnormal Change from Baseline of Vital Signs up to Day 23 | Day 1, 3, 8, 13, 16, 18, 23 |
| Cmax of BIIB074 Metabolites M13, M14, and M16 | Day 1 through Day 8, Day 16 through Day 23 |
| AUCinf of BIIB074 Metabolites M13, M14, and M16 | Day 1 through Day 8, Day 16 through Day 23 |
| AUClast of BIIB074 Metabolites M13, M14, and M16 | Day 1 through Day 8, Day 16 through Day 23 |
| Tmax of BIIB074 Metabolites M13, M14, and M16 | Day 1 through Day 8, Day 16 through Day 23 |
| Tlast of BIIB074 Metabolites M13, M14, and M16 | Day 1 through Day 8, Day 16 through Day 23 |
| T1/2 of BIIB074 Metabolites M13, M14, and M16 | Day 1 through Day 8, Day 16 through Day 23 |
| Metabolite-to-Parent Ratio in AUC (MRauc) of BIIB074 Metabolites M13, M14, and M16 | Day 1 through Day 8, Day 16 through Day 23 |
| Number of Participants with Abnormal Change from Baseline in Columbia Suicide Severity Rating (C-SSRS) scale | C-SSRS is a suicidal ideation rating used to evaluate suicidality in children ages 12 and up. It rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent | Day 8, 23, and once between Day 29-32 |
| D009930 |
| Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |