Major Depressive Disorder, Healthy Volunteer
Conditions
Brief summary
The study will assess the safety, tolerability, and pharmacokinetics of basimglurant compared to placebo after multiple ascending oral doses for up to 22 days in healthy subjects and in patients with MDD on stable selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) background therapy.
Interventions
DRUGBasimglurant
Participants will receive once-daily oral basimglurant capsules in a multiple ascending dose regimen. Basimglurant dose will be titrated over 22 days; dose escalations will be separated by at least 4 days, with the final dose administered for a minimum of 14 days. The minimum starting dose will be 1.5 mg, which can be titrated up to a maximum dose of 4.0 mg. Intrapatient dose increments will not exceed 1.0 mg every 4 days.
DRUGPlacebo
Participants will receive 22 days of once-daily oral matching placebo capsules.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 to 65 years of age, inclusive * Body weight at least 50 kg * Healthy male or female subjects (Healthy Cohorts) * Body mass index (BMI) 18 to 30 kg/m\^2, inclusive (Healthy Cohorts) * Nonsmoker for at least 90 days prior to dosing (Healthy Cohorts) * Primary diagnosis of MDD without psychotic features (MDD Cohort) * BMI 18 to 35 kg/m\^2, inclusive (MDD Cohort) * Current partial response to ongoing SSRI or SNRI antidepressant treatment at an adequate dose and for at least 4 weeks (MDD Cohort) * Clinical Global Impression of Severity (CGI-S) score 3 or greater (MDD Cohort) * Other regimens stable for at least 8 weeks prior to screening (MDD Cohort)
Exclusion criteria
* Pregnant or lactating women * History of alcohol or substance abuse in the past 6 months * Hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) * Clinically relevant electrocardiogram (ECG) abnormalities or a personal or family history of congenital long QT syndrome * Participation in an investigational study within 90 days of screening * Blood donation over 500 mL within 3 months of screening * Hypersensitivity to any study medication or excipients * Psychotic symptoms or comorbid mood disorder * Significant suicide risk * Major illness within 1 month before screening, or febrile illness within 1 week (Healthy Cohorts) * Average alcohol consumption of more than 2 units per day (Healthy Cohorts) * Multi-drug therapy for depression including antidepressants or adjunctive medications (MDD Cohort) * Prior use of basimglurant (MDD Cohort) * Cigarette use of greater than 1 pack per day (MDD Cohort)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: Suicidality as assessed using the Columbia Suicide Severity Rating Scale (C-SSRS) | Up to 10 weeks |
| Safety: Sleep habits as assessed using a participant-recorded sleep diary | Up to 21 days |
| Safety: Incidence of adverse events (AEs) | Up to 10 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Time to maximum plasma concentration (Tmax) | Post dose on Day 1 and Day 22 (or final dose) |
| Pharmacokinetics: Trough plasma concentration (Ctrough) | Post dose on Day 1 and Day 22 (or final dose) |
| Pharmacokinetics: Maximum plasma concentration (Cmax) | Post dose on Day 1 and Day 22 (or final dose) |
| Safety: QT interval corrected using the Fridericia method (QTcF) | Up to 10 weeks |
| Pharmacokinetics: Apparent terminal elimination half-life (t1/2) | Post dose on Day 22 (or final dose) |
| Pharmacokinetics: Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) | Post dose on Day 1 |
| Pharmacokinetics: Area under the plasma concentration-time curve over the dosing interval (AUC0-tau) | Post dose on Day 22 (or final dose) |
Countries
United States
Outcome results
None listed