Trial to Determine the Maximum Tolerated Dose (MTD) Based on Safety and Tolerability, of Org 26576 in Participants With Major Depressive Disorder (174001/P05704/MK-8777-001)

Merck Sharp & Dohme LLC54 enrolled

Overview

Trial to determine the maximum tolerated dose (MTD) based on safety and tolerability of MK-8777 (Org 26576, SCH 900777) in participants with major depressive disorder.

This is a randomized, placebo-controlled, safety and tolerability study examining MK-8777 in participants with major depressive disorder. In Part I of the trial, four different cohorts of six participants each will receive multiple rising doses of MK-8777 (ranging from 100 mg twice a day \[BID\] to 300 mg BID) or placebo for up to 16 days. In Part 2, a new cohort of participants will be randomly assigned to receive 100 mg BID of MK-8777, 400 mg BID of MK-8777, or placebo. Following titration (3 days per step), participants will be maintained on the assigned BID dose until Day 27, followed by one day of once a day (QD) dosing, for a total of 28 days. There were 11 treatment arms in total for Part 1 and Part 2 (see Interventions).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Depression

Interventions

MK-8777DRUG

Orally administered capsules containing either 50 mg or 100 mg MK-8777.

PlaceboDRUG

Orally administered matching placebo capsules.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Female who is non-pregnant, nonlactating, using an acceptable method of birth control, or is not of child-bearing potential; * be diagnosed with current major depressive disorder either mild or severe, as evidenced by a score of at least 9 but not more than 20 on the Quick Inventory of Depression Symptomatology - Clinician Rated (QIDS-C); * be anti-depressant naïve; * be able to refrain from all use of grapefruit containing products from the time of admission until the last assessment is performed at discharge; * smokes less than or equal to 10 cigarettes or equivalent daily. Exclusion Criteria: * has any current and primary Axis I disorder other than major depressive disorder; * has any history of bipolar I or II disorder, dysthymia, psychotic depression, psychotic disorders, posttraumatic stress disorder, borderline personality disorder, obsessive compulsive disorder, or eating disorder; * the duration of the current depressive episode is longer than 2 years at screening; * has any history of a significant suicide attempt, or poses a current risk of attempting suicide; * is known to be human immunodeficiency virus (HIV) positive, or positive for hepatitis B surface antigen or hepatitis A antibodies or hepatitis C total antibodies; * has any clinically significant concurrent endocrine, renal, respiratory, cardiovascular, hematological, immunological, cerebrovascular, neurological, malignancy, or any other concurrent medical condition, or has any history of diabetes mellitus; * donation of blood within 60 days prior to the anticipated first dose of trial medication.

Outcomes

Primary Outcomes

Part 1: Number of Participants With Moderate Intensity Adverse Events (AEs)

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. A moderate intensity AE is defined as an AE that causes no significant interference with functioning.

Time frame: Up to 7 days following the last dose of study drug (Up to 23 days)

Part 1: Number of Participants With Serious Adverse Events (SAEs)

An SAE is defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

Time frame: Up to 30 days following the last dose of study drug (Up to 46 days)

Part 1: Number of Participants With AEs Leading to Discontinuation of Study Drug

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Discontinuation refers to discontinuation of study drug (MK-8777 or Placebo).

Time frame: Up to the last dose of study drug (Up to 16 days)

Part 2: Number of Participants With AEs

Time frame: Up to 7 days following the last dose of study drug (Up to 35 days)

Part 2: Number of Participants With AEs Leading to Discontinuation of Study Drug

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Discontinuation refers to discontinuation of study drug (MK-8777 or Placebo).

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Part 1: Change From Baseline in the Montgomery-Ashberg Depression Rating Scale (MADRS)

The MADRS is a 10-item scale designed to assess the severity of depression. The questionnaire includes questions on the following symptoms: Apparent sadness, Reported sadness, Inner tension, Reduced sleep, Reduced appetite, Concentration difficulties, Lassitude, Inability to feel, Pessimistic thoughts, and Suicidal thoughts. Each of the 10 symptoms are rated on a scale of 1 to 6, with 1=absent to 6=severe. The MADRS score can range from 0 (symptoms absent) to 60 (severe depression), with a higher score indicating more severe depression.

Time frame: Baseline and end of treatment (Up to Day 16)

Part 2: Change From Baseline in the MADRS

Time frame: Baseline and end of treatment (Up to Day 28)