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)

Depression Clinical Trial

Official title:

Single Center, Randomized, Placebo-Controlled Trial to Establish Maximum Tolerated Dose, Optimal Titration Schedule, Safety, Tolerability, and Pharmacokinetics of Org 26576 in Patients Diagnosed With Major Depressive Disorder (Protocol No. P174001)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00610649
• Other study ID #: P05704
• Secondary ID: 174001
• Status: Completed
• Phase: Phase 2
• Start date: September 20, 2007
• Est. completion date: December 10, 2008

Study information

• Verified date: October 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 10, 2008
• Est. primary completion date: November 18, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• MK-8777
Orally administered capsules containing either 50 mg or 100 mg MK-8777.
• Placebo
Orally administered matching placebo capsules.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 7 days following the last dose of study drug (Up to 23 days)
Primary	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.	Up to 30 days following the last dose of study drug (Up to 46 days)
Primary	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).	Up to the last dose of study drug (Up to 16 days)
Primary	Part 2: Number of Participants With 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.	Up to 7 days following the last dose of study drug (Up to 35 days)
Primary	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).	Up to the last dose of study drug (Up to 28 days)
Secondary	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.	Baseline and end of treatment (Up to Day 16)
Secondary	Part 2: Change From Baseline in the 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.	Baseline and end of treatment (Up to Day 28)