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)

NCT ID: NCT00610649

Last Updated: 2018-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-20
• Study Completion Date: 2008-12-10

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.

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).

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

MK-8777

Intervention Type: DRUG

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

Part 1: Block A Placebo

Participants receive placebo BID for a total of 16 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Orally administered matching placebo capsules.

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.

Group Type: EXPERIMENTAL

MK-8777

Intervention Type: DRUG

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

Part 1: Block B Placebo

Participants receive placebo BID for a total of 13 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Orally administered matching placebo capsules.

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.

Group Type: EXPERIMENTAL

MK-8777

Intervention Type: DRUG

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

Part 1: Block C Placebo

Participants receive placebo BID for a total of 10 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Orally administered matching placebo capsules.

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.

Group Type: EXPERIMENTAL

MK-8777

Intervention Type: DRUG

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

Part 1: Block D Placebo

Participants receive placebo BID for a total of 13 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Orally administered matching placebo capsules.

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.

Group Type: EXPERIMENTAL

MK-8777

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

MK-8777

Intervention Type: DRUG

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

Part 2: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Orally administered matching placebo capsules.

Interventions

MK-8777

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

Intervention Type: DRUG

Placebo

Orally administered matching placebo capsules.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

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.

Reference Type: DERIVED

PMID: 34510411 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22954616 (View on PubMed)

Other Identifiers

174001

Identifier Type: OTHER

Identifier Source: secondary_id

P05704

Identifier Type: -

Identifier Source: org_study_id