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

November 1, 2016 updated by: Hoffmann-La Roche

A Single-Center, Randomized, Investigator/Participant-Blind, Placebo-Controlled, Multiple-Ascending Dose, Semi-Sequential Adaptive Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Basimglurant Following Oral Administration in Healthy Subjects and in Patients With Major Depressive Disorder

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Garden Grove, California, United States, 92845

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Basimglurant: Healthy Cohort (1)
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.
Drug: Basimglurant
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.
Experimental: Basimglurant: Healthy Cohort (2)
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.
Drug: Basimglurant
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.
Experimental: Basimglurant: Healthy Cohort (3)
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.
Drug: Basimglurant
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.
Experimental: Basimglurant: Healthy Cohort (4)
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.
Drug: Basimglurant
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.
Experimental: Basimglurant: MDD Cohort (5)
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.
Drug: Basimglurant
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.
Placebo Comparator: Placebo: Healthy Cohorts (1 to 4)
Healthy participants will receive a 22-day regimen of matching placebo capsules.
Drug: Placebo
Participants will receive 22 days of once-daily oral matching placebo capsules.
Placebo Comparator: Placebo: MDD Cohort (5)
Participants with MDD will receive a 22-day regimen of matching placebo capsules.
Drug: Placebo
Participants will receive 22 days of once-daily oral matching placebo capsules.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Safety: Incidence of adverse events (AEs)
Time Frame: Up to 10 weeks
Up to 10 weeks
Safety: Suicidality as assessed using the Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame: Up to 10 weeks
Up to 10 weeks
Safety: Sleep habits as assessed using a participant-recorded sleep diary
Time Frame: Up to 21 days
Up to 21 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Pharmacokinetics: Maximum plasma concentration (Cmax)
Time Frame: Post dose on Day 1 and Day 22 (or final dose)
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)
Time Frame: Post dose on Day 1
Post dose on Day 1
Pharmacokinetics: Area under the plasma concentration-time curve over the dosing interval (AUC0-tau)
Time Frame: Post dose on Day 22 (or final dose)
Post dose on Day 22 (or final dose)
Pharmacokinetics: Time to maximum plasma concentration (Tmax)
Time Frame: Post dose on Day 1 and Day 22 (or final dose)
Post dose on Day 1 and Day 22 (or final dose)
Pharmacokinetics: Trough plasma concentration (Ctrough)
Time Frame: Post dose on Day 1 and Day 22 (or final dose)
Post dose on Day 1 and Day 22 (or final dose)
Pharmacokinetics: Apparent terminal elimination half-life (t1/2)
Time Frame: Post dose on Day 22 (or final dose)
Post dose on Day 22 (or final dose)
Safety: QT interval corrected using the Fridericia method (QTcF)
Time Frame: Up to 10 weeks
Up to 10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 29, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 1, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 4, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 2, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NP29583

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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