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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Depression

Treatments: Drug: Placebo; Drug: MK-8777

Study type: Interventional

Funder types: Industry

Identifiers

NCT00610649

174001 (Other Identifier)

P05704

Details and patient eligibility

About

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.

Full 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).

Enrollment: 54 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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54 participants in 11 patient groups, including a placebo group

Part 1: Block A MK-8777

Experimental group

Description:

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.

Treatment:

Drug: MK-8777

Part 1: Block A Placebo

Placebo Comparator group

Description:

Participants receive placebo BID for a total of 16 days.

Treatment:

Drug: Placebo

Part 1: Block B MK-8777

Experimental group

Description:

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.

Treatment:

Drug: MK-8777

Part 1: Block B Placebo

Placebo Comparator group

Description:

Participants receive placebo BID for a total of 13 days.

Treatment:

Drug: Placebo

Part 1: Block C MK-8777

Experimental group

Description:

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.

Treatment:

Drug: MK-8777

Part 1: Block C Placebo

Placebo Comparator group

Description:

Participants receive placebo BID for a total of 10 days.

Treatment:

Drug: Placebo

Part 1: Block D MK-8777

Experimental group

Description:

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.

Treatment:

Drug: MK-8777

Part 1: Block D Placebo

Placebo Comparator group

Description:

Participants receive placebo BID for a total of 13 days.

Treatment:

Drug: Placebo

Part 2: MK-8777 200 mg

Experimental group

Description:

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.

Treatment:

Drug: MK-8777

Part 2: MK-8777 800 mg

Experimental group

Description:

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.

Treatment:

Drug: MK-8777

Part 2: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo