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

January 28, 2008
June 30, 2014
September 2007
November 2008   (final data collection date for primary outcome measure)
  • 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).
• To assess the safety and tolerability of two different doses of Org 26576 in patients with major depressive disorder over a 28-day dosing and observation period. [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00610649 on ClinicalTrials.gov Archive Site
  • 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.
To explore the pharmacokinetic (PK) behavior of multiple rising doses of Org 26576 in plasma and CSF. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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)
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)

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).

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Depression
  • Drug: MK-8777
    Orally administered capsules containing either 50 mg or 100 mg MK-8777.
  • Drug: Placebo
    Orally administered matching placebo capsules.
  • 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.
    Intervention: Drug: MK-8777
  • Placebo Comparator: Part 1: Block A Placebo
    Participants receive placebo BID for a total of 16 days.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: MK-8777
  • Placebo Comparator: Part 1: Block B Placebo
    Participants receive placebo BID for a total of 13 days.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: MK-8777
  • Placebo Comparator: Part 1: Block C Placebo
    Participants receive placebo BID for a total of 10 days.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: MK-8777
  • Placebo Comparator: Part 1: Block D Placebo
    Participants receive placebo BID for a total of 13 days.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: 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.
    Intervention: Drug: 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.
    Intervention: Drug: Placebo
Nations KR, Dogterom P, Bursi R, Schipper J, Greenwald S, Zraket D, Gertsik L, Johnstone J, Lee A, Pande Y, Ruigt G, Ereshefsky L. Examination of Org 26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo-controlled trial. J Psychopharmacol. 2012 Dec;26(12):1525-39. doi: 10.1177/0269881112458728. Epub 2012 Sep 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
54
December 2008
November 2008   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00610649
P05704, 174001
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP