Healthy volunteers Not Applicable
Conditions
Interventions
Experimental: Part A (Itraconazole)
Participants will receive BIIB113, orally, once daily (OD), on Days 1 and 11 along with itraconazole, orally, OD, from Days 7 to 16.
Experimental: Part B (Phenytoi
Sponsors
Biogen (United Kingdom)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Body mass index (BMI) between 18 and 30 kilograms per square meter (kg/m^2) inclusive 2. Weight =50 kg at Screening 3. Negative severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) test result within 5 days of Day -1 prior to randomisation 4. Infertile males as defined by Clinical Trials Facilitation and Coordination Group (CTFG) guidelines: 4.1. Permanently sterile by bilateral orchidectomy 4.2. Vasectomised males defined as follows: 4.2.1. Minimum of 12 weeks after successful vasectomy surgical procedure, and 4.2.2. Documentation of confirmation of successful vasectomy by postvasectomy semen analysis – information collected at least 12 weeks after the surgery 5. All females of childbearing potential must practice contraception
Exclusion criteria
Exclusion criteria: 1. Suicidal ideation, per the Investigator’s clinical judgement, with some intent to act within 6 months prior to the start of Screening, per the Investigator’s clinical judgement or based on the C-SSRS, corresponding to a response of ‘Yes’ on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or a history of suicidal behaviour within 1 year prior to the start of Screening. Participants reporting suicidal ideation with intent to act or suicidal behaviour prior to the Day 1 visit should be excluded. 2. History of systemic hypersensitivity reaction to BIIB113, itraconazole (Part A), phenytoin (Part B), midazolam (Part C), other related drugs, or the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study. 3. Any vaccination within 10 days prior to Day -1 or intention to be vaccinated within 10 days after the last dose of study treatment. 4. Use of any hormonal oral contraceptives, systemically acting hormone-releasing contraceptive implants (excluding intrauterine devices), and hormone-replacement medication. 5. Use of any prescription medication, over-the-counter oral medication (excluding acetaminophen [= 2 g/day]) or dietary and herbal supplements that are not inducers or inhibitors of drug metabolising enzymes or drug transporters within 7 days prior to Day -1, and an unwillingness or inability to refrain from this use during study participation, unless specifically permitted elsewhere within the protocol. 6. Use of any prescription medication, over-the-counter oral medication, or dietary and herbal supplements (e.g., St. John’s wort) that are a known inducer or inhibitor of drug metabolising enzymes (including but not limited to CYP3A) or drug transporters within 28 days of Day -1 and an unwillingness to refrain from use during study participation. NOTE: Other protocol-defined inclusion/exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Parts A and B: Maximum observed concentration (Cmax) of BIIB113 assessed using blood samples at predose and multiple timepoints postdose up to Day 17 (Part A) and at predose and multiple timepoints postdose up to Day 21 (Part B) 2. Part C: Cmax of midazolam assessed using blood samples at predose and multiple timepoints postdose up to Day 16 3. Parts A and B: Area under the concentration-time curve from time zero to time of the last measurable concentration (AUClast) of BIIB113 assessed using blood samples at predose and multiple timepoints postdose up to Day 17 (Part A) and at predose and multiple timepoints postdose up to Day 21(Part B) 4. Part C: AUClast of midazolam assessed using blood samples at predose and multiple timepoints postdose up to Day 16 5. Part A and B: Area under the concentration-time curve from time zero to infinity (AUC0-inf) of BIIB113 assessed using blood samples at predose and multiple timepoints postdose up to Day 17 (Part A) and at predose and multiple timepoints postdose up to Day 21 (Part B) 6. Part C: AUC0-inf of midazolam assessed using blood samples at predose and multiple timepoints postdose up to Day 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Parts A, B, and C: Number of participants with adverse events (AEs) as assessed using data recorded on the electronic case report forms (eCRFs) from Day 1 up to the end of study (up to approximately 26 days) 2. Parts A, B, and C: Number of participants with serious adverse events (SAEs) assessed using data recorded on the SAE form from signing of informed consent up to the end of study (up to approximately 54 days) 3. Parts A, B, and C: Number of participants with clinically significant change from baseline in clinical laboratory parameters, vital signs, 12-lead electrocardiogram (ECG), and Columbia Suicide Severity Rating Scale (C-SSRS) score as assessed by the investigator from screening to end of study (up to approximately 54 days) 4. Parts A and B: Terminal elimination half-life (t½) of BIIB113 assessed using blood samples at predose and multiple timepoints postdose up to Day 17 (Part A) and at predose and multiple timepoints postdose up to Day 21 (Part B) 5. Part C: t½ of midazolam and 1-hydroxymidazolam assessed using blood samples at predose and multiple timepoints postdose up to Day 16 6. Parts A and B: Apparent total body clearance (CL/F) of BIIB113 assessed using blood samples at predose and multiple timepoints postdose up to Day 17 (Part A) and at predose and multiple timepoints postdose up to Day 21 (Part B) 7. Part C: CL/F of midazolam assessed using blood samples at predose and multiple timepoints postdose up to Day 16 8. Parts A and B: Time to maximum observed concentration (Tmax) of BIIB113 assessed using blood samples at predose and multiple timepoints postdose up to Day 17 (Part A) and at predose and multiple timepoints postdose up to Day 21 (Part B) 9. Part C: Tmax of midazolam and 1-hydroxymidazolam assessed using blood samples at predose and multiple timepoints postdose up to Day 16 10. Parts A and B: Apparent volume of distribution during the terminal elimination phase (Vz/F) of BIIB113 assessed using blood samples at predose and multiple ti | — |
Countries
England, United Kingdom
Outcome results
None listed