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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00610649
First received: January 28, 2008
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Depression
Drug: MK-8777
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Part 1: Number of Participants With Moderate Intensity Adverse Events (AEs) [ Time Frame: Up to 7 days following the last dose of study drug (Up to 23 days) ] [ Designated as safety issue: Yes ]
    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.

  • Part 1: Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days following the last dose of study drug (Up to 46 days) ] [ Designated as safety issue: Yes ]
    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.

  • Part 1: Number of Participants With AEs Leading to Discontinuation of Study Drug [ Time Frame: Up to the last dose of study drug (Up to 16 days) ] [ Designated as safety issue: Yes ]
    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).

  • Part 2: Number of Participants With AEs [ Time Frame: Up to 7 days following the last dose of study drug (Up to 35 days) ] [ Designated as safety issue: Yes ]
    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.

  • Part 2: Number of Participants With AEs Leading to Discontinuation of Study Drug [ Time Frame: Up to the last dose of study drug (Up to 28 days) ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Part 1: Change From Baseline in the Montgomery-Ashberg Depression Rating Scale (MADRS) [ Time Frame: Baseline and end of treatment (Up to Day 16) ] [ Designated as safety issue: No ]
    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.

  • Part 2: Change From Baseline in the MADRS [ Time Frame: Baseline and end of treatment (Up to Day 28) ] [ Designated as safety issue: No ]
    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.


Enrollment: 54
Study Start Date: September 2007
Study Completion Date: December 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Block A MK-8777
Participants receive MK-8777 initiated at 100 mg BID and titrated to a maximum of 600 mg BID. Participants receive MK-8777 for a total of 16 days.
Drug: MK-8777
Orally administered capsules containing either 50 mg or 100 mg MK-8777.
Placebo Comparator: Part 1: Block A Placebo
Participants receive placebo BID for a total of 16 days.
Drug: Placebo
Orally administered matching placebo capsules.
Experimental: Part 1: Block B MK-8777
Participants receive MK-8777 initiated at 200 mg BID and titrated to a maximum of 600 mg BID. Participants receive MK-8777 for a total of 13 days.
Drug: MK-8777
Orally administered capsules containing either 50 mg or 100 mg MK-8777.
Placebo Comparator: Part 1: Block B Placebo
Participants receive placebo BID for a total of 13 days.
Drug: Placebo
Orally administered matching placebo capsules.
Experimental: Part 1: Block C MK-8777
Participants receive MK-8777 initiated at 300 mg BID and titrated to a maximum of 600 mg BID. Participants receive MK-8777 for a total of 10 days.
Drug: MK-8777
Orally administered capsules containing either 50 mg or 100 mg MK-8777.
Placebo Comparator: Part 1: Block C Placebo
Participants receive placebo BID for a total of 10 days.
Drug: Placebo
Orally administered matching placebo capsules.
Experimental: Part 1: Block D MK-8777
Participants receive MK-8777 initiated at 100 mg BID and titrated to a maximum dose determined by the results of Block A. Participants receive MK-8777 for a total of 13 days.
Drug: MK-8777
Orally administered capsules containing either 50 mg or 100 mg MK-8777.
Placebo Comparator: Part 1: Block D Placebo
Participants receive placebo BID for a total of 13 days.
Drug: Placebo
Orally administered matching placebo capsules.
Experimental: Part 2: MK-8777 200 mg
Participants receive MK-8777 100 mg BID for 27 days followed by one day of 100 mg QD. Participants receive MK-8777 for a total of 28 days.
Drug: MK-8777
Orally administered capsules containing either 50 mg or 100 mg MK-8777.
Experimental: Part 2: MK-8777 800 mg
Participants receive MK-8777 200 mg BID for 3 days followed by 400 mg BID for 24 days followed by one day of 400 mg QD. Participants receive MK-8777 for a total of 28 days.
Drug: MK-8777
Orally administered capsules containing either 50 mg or 100 mg MK-8777.
Placebo Comparator: Part 2: Placebo
Participants receive placebo BID for 27 days followed by one day of placebo QD. Participants receive placebo for 28 days.
Drug: Placebo
Orally administered matching placebo capsules.

Detailed 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).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00610649     History of Changes
Other Study ID Numbers: P05704, 174001
Study First Received: January 28, 2008
Results First Received: May 27, 2014
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
randomized
placebo controlled
maximum tolerated dose

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 01, 2014