A Study of the Safety, Tolerability, and Pharmacokinetics of Multiple-Ascending Dose Basimglurant in Healthy Subjects and in Patients With Major Depressive Disorder (MDD)

Phase 1

Completed

• Conditions: Major Depressive Disorder, Healthy Volunteer
• Interventions: Drug: Basimglurant; Drug: Placebo

• Registration Number: NCT02433093
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2015-04-29
• Study First Submitted QC: 2015-05-01
• Study First Posted: 2015-05-04
• Primary Completion: 2015-09
• Study Completion: 2015-09
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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)

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Basimglurant: Healthy Cohort (2)	Basimglurant	Healthy participants assigned to basimglurant will receive a 22-day ascending dose regimen. The dosing scheme for Cohort 2 will be selected in accordance with decision criteria on the basis of the incidence of severe AEs in Cohort 1.
Basimglurant: Healthy Cohort (3)	Basimglurant	Healthy participants assigned to basimglurant will receive a 22-day ascending dose regimen. The dosing scheme for Cohort 3 will be selected in accordance with decision criteria on the basis of the incidence of severe AEs in preceding Cohorts 1 and 2.
Placebo: Healthy Cohorts (1 to 4)	Placebo	Healthy participants will receive a 22-day regimen of matching placebo capsules.
Placebo: MDD Cohort (5)	Placebo	Participants with MDD will receive a 22-day regimen of matching placebo capsules.
Basimglurant: Healthy Cohort (1)	Basimglurant	Healthy participants assigned to basimglurant will receive a 22-day ascending dose regimen. Cohort 1 will receive a prespecified titration scheme; however, adaptive titration schemes may be applied in subsequent cohorts.
Basimglurant: Healthy Cohort (4)	Basimglurant	Healthy participants assigned to basimglurant will receive a 22-day ascending dose regimen. The dosing scheme for Cohort 4 will be selected in accordance with decision criteria on the basis of the incidence of severe AEs in preceding Cohorts 1, 2, and 3.
Basimglurant: MDD Cohort (5)	Basimglurant	Participants with MDD assigned to basimglurant will receive a 22-day ascending dose regimen. The dosing scheme for Cohort 5 may differ from those previously evaluated; however, the titration steps and the highest dose tested will remain equal to or lower than the doses tested in Cohorts 1 to 4.

Primary Outcome Measures

Name	Time	Method
Safety: Incidence of adverse events (AEs)	Up to 10 weeks
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

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics: Maximum plasma concentration (Cmax)	Post dose on Day 1 and 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)
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: Apparent terminal elimination half-life (t1/2)	Post dose on Day 22 (or final dose)
Safety: QT interval corrected using the Fridericia method (QTcF)	Up to 10 weeks