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)

NCT00610649 | Completed Phase 2 Results

• 2 other identifiers: P05704174001
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Depression

Keywords

randomized; placebo controlled; maximum tolerated dose

Outcome Measures

Primary Outcomes (5)

• 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)

• 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)

• 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)

• 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)

• 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 Outcomes (2)

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

  Baseline and end of treatment (Up to Day 16)

• Part 2: Change From Baseline in the MADRS

  Baseline and end of treatment (Up to Day 28)

Study Arms (11)

Part 1: Block A MK-8777

EXPERIMENTAL

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

Part 1: Block A Placebo

PLACEBO COMPARATOR

Participants receive placebo BID for a total of 16 days.

Drug: Placebo

Part 1: Block B MK-8777

EXPERIMENTAL

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

Part 1: Block B Placebo

PLACEBO COMPARATOR

Participants receive placebo BID for a total of 13 days.

Drug: Placebo

Part 1: Block C MK-8777

EXPERIMENTAL

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

Part 1: Block C Placebo

PLACEBO COMPARATOR

Participants receive placebo BID for a total of 10 days.

Drug: Placebo

Part 1: Block D MK-8777

EXPERIMENTAL

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

Part 1: Block D Placebo

PLACEBO COMPARATOR

Participants receive placebo BID for a total of 13 days.

Drug: Placebo

Part 2: MK-8777 200 mg

EXPERIMENTAL

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

Part 2: MK-8777 800 mg

EXPERIMENTAL

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

Part 2: Placebo

PLACEBO COMPARATOR

Participants receive placebo BID for 27 days followed by one day of placebo QD. Participants receive placebo for 28 days.

Drug: Placebo

Interventions

MK-8777 DRUG

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

Part 1: Block A MK-8777; Part 1: Block B MK-8777; Part 1: Block C MK-8777; Part 1: Block D MK-8777; Part 2: MK-8777 200 mg; Part 2: MK-8777 800 mg

Placebo DRUG

Orally administered matching placebo capsules.

Part 1: Block A Placebo; Part 1: Block B Placebo; Part 1: Block C Placebo; Part 1: Block D Placebo; Part 2: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3.

  PMID: 34510411 DERIVED

• 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.

  PMID: 22954616 DERIVED

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2008
• First Posted: February 8, 2008
• Study Start: September 20, 2007
• Primary Completion: November 18, 2008
• Study Completion: December 10, 2008
• Last Updated: November 6, 2018
• Results First Posted: July 2, 2014

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share