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

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: December 9, 2013
Last verified: December 2013
  Purpose

Trial to determine the maximum tolerated dose (MTD) based

on safety and tolerability of Org 26576 in participants with

major depressive disorder.


Condition Intervention Phase
Depression
Drug: Org 26576
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Part 1: Percentage of Participants with Moderate Intensity Adverse Events (AEs) [ Time Frame: Baseline up to 30 days following the last dose of study drug (up to day 46) ] [ Designated as safety issue: Yes ]
  • Part 1: Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 30 days following the last dose of study drug (up to day 46) ] [ Designated as safety issue: Yes ]
  • Part 1: Percentage of Participants with AEs Leading to Discontinuation [ Time Frame: Baseline up to the last dose of study drug (up to day 16) ] [ Designated as safety issue: Yes ]
  • Part 2: Percentage of Participants with AEs [ Time Frame: Baseline up to 30 days following the last dose of study drug (up to day 58) ] [ Designated as safety issue: Yes ]
  • Part 2: Percentage of Participants with AEs Leading to Discontinuation [ Time Frame: Baseline up to the last dose of study drug (up to day 28) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Part 1: Change from Baseline in the Montgomery-Ashberg Depression Rating Scale (MADRS) from Baseline to End of Treatment [ Time Frame: Baseline and end of treatment (up to day 16) ] [ Designated as safety issue: No ]
  • Part 2: Change from Baseline in the MADRS from Baseline to End of Treatment [ Time Frame: Baseline and end of treatment (up to day 28) ] [ Designated as safety issue: No ]

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-Org 26576
Participants receive Org 26576 initiated at 100 mg BID and titrated to a maximum of 600 mg BID. Participants receive study drug for a total of 16 days.
Drug: Org 26576
Orally administered capsules containing either 50 mg or 100 mg Org 26576.
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-Org 26576
Participants receive Org 26576 initiated at 200 mg BID and titrated to a maximum of 600 mg BID. Participants receive study drug for a total of 13 days.
Drug: Org 26576
Orally administered capsules containing either 50 mg or 100 mg Org 26576.
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-Org 26576
Participants receive Org 26576 initiated at 300 mg BID and titrated to a maximum of 600 mg BID. Participants receive study drug for a total of 10 days.
Drug: Org 26576
Orally administered capsules containing either 50 mg or 100 mg Org 26576.
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-Org 26576
Participants receive Org 26576 initiated at 100 mg BID and titrated to a maximum dose determined by the results of Block A. Participants receive study drug for a total of 13 days.
Drug: Org 26576
Orally administered capsules containing either 50 mg or 100 mg Org 26576.
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: Org 26576 100 mg
Participants receive Org 26576 100 mg BID for 27 days followed by one day of 100 mg total daily dose. Participants receive study drug for a total of 28 days.
Drug: Org 26576
Orally administered capsules containing either 50 mg or 100 mg Org 26576.
Experimental: Part 2: Org 26576 400 mg
Participants receive Org 26576 200 mg BID for 27 days followed by one day of 400 mg total daily dose. Participants receive study drug for a total of 28 days.
Drug: Org 26576
Orally administered capsules containing either 50 mg or 100 mg Org 26576.
Placebo Comparator: Part 2: Placebo
Participants receive placebo BID for 27 days and placebo once on day 28.
Drug: Placebo
Orally administered matching placebo capsules.

Detailed Description:

This is a randomized, placebo-controlled, safety and tolerability study examining Org 26576 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 Org 26576 (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 Org 26576, 400 mg BID of Org 26576, 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 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
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
Last Updated: December 9, 2013
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 April 17, 2014