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A Fixed Dose Study of Adjunctive Treatment to Antidepressant Therapy for Adults With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT01173601
Recruitment Status : Completed
First Posted : August 2, 2010
Results First Posted : April 17, 2018
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Major Depressive Disorder
Interventions: Drug: LY2216684
Drug: Placebo
Drug: SSRI

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The first 3 weeks was a double-blind adjunctive placebo lead-in Confirmation Phase during which participants continued their SSRI with adjunctive placebo. If randomization criteria were met, participants were randomized to receive LY2216684 12 mg, 18 mg, or placebo. If criteria were not met, participants continued on placebo to maintain the blind.

Reporting Groups
  Description
Placebo + SSRI (Pre-Randomized Participants) Placebo: Administered orally, once daily for 3 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
12 mg LY2216684 + SSRI (Randomized Participants) LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI
18 mg LY2216684 + SSRI (Randomized Participants) LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo + SSRI (Randomized Participants) Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Placebo + SSRI (Non-Randomized Participants) Placebo: Administered orally, once daily for 8 weeks

Participant Flow for 2 periods

Period 1:   Confirmation (CF) Phase, 3 Weeks
    Placebo + SSRI (Pre-Randomized Participants)   12 mg LY2216684 + SSRI (Randomized Participants)   18 mg LY2216684 + SSRI (Randomized Participants)   Placebo + SSRI (Randomized Participants)   Placebo + SSRI (Non-Randomized Participants)
STARTED   1416   0   0   0   0 
Entered Discontinuation Phase   21 [1]   0   0   0   0 
COMPLETED   1328 [2]   0   0   0   0 
NOT COMPLETED   88   0   0   0   0 
Adverse Event                23                0                0                0                0 
Lack of Efficacy                9                0                0                0                0 
Lost to Follow-up                7                0                0                0                0 
Physician Decision                3                0                0                0                0 
Protocol Violation                15                0                0                0                0 
Withdrawal by Subject                25                0                0                0                0 
Sponsor Decision                6                0                0                0                0 
[1] Participants who discontinued the CF Phase had the option to enter the DC phase.
[2] Participants who completed the CF Phase entered the AT Phase.

Period 2:   Adjunctive Treatment (AT) Phase, 8 Weeks
    Placebo + SSRI (Pre-Randomized Participants)   12 mg LY2216684 + SSRI (Randomized Participants)   18 mg LY2216684 + SSRI (Randomized Participants)   Placebo + SSRI (Randomized Participants)   Placebo + SSRI (Non-Randomized Participants)
STARTED   0   231   230   240   627 
Entered Taper Discontinuation Phase   0   100 [1]   107 [1]   0   0 
Entered Abrupt Discontinuation Phase   0   100 [2]   108 [2]   221 [2]   586 [2] 
COMPLETED   0   196   197   210   559 
NOT COMPLETED   0   35   33   30   68 
Adverse Event                0                10                15                7                14 
Lack of Efficacy                0                10                6                8                9 
Lost to Follow-up                0                3                0                2                9 
Physician Decision                0                2                0                2                1 
Protocol Violation                0                1                5                4                5 
Withdrawal by Subject                0                9                7                5                24 
Sponsor Decision                0                0                0                2                6 
[1] Participants who completed the AT Phase or discontinued early entered the taper DC Phase.
[2] Participants who completed the AT Phase or discontinued early entered the abrupt DC Phase.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed the Confirmation Phase and were randomized to adjunctive LY2216684 or adjunctive placebo or who did not meet randomization criteria and continued on placebo to maintain the blind.

Reporting Groups
  Description
12 mg LY2216684 + SSRI (Randomized Participants) LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
18 mg LY2216684 + SSRI (Randomized Participants) LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo + SSRI (Randomized Participants) Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Placebo + SSRI (Non-Randomized Participants) Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Total Total of all reporting groups

Baseline Measures
   12 mg LY2216684 + SSRI (Randomized Participants)   18 mg LY2216684 + SSRI (Randomized Participants)   Placebo + SSRI (Randomized Participants)   Placebo + SSRI (Non-Randomized Participants)   Total 
Overall Participants Analyzed 
[Units: Participants]
 231   230   240   627   1328 
Age 
[Units: Years]
Mean (Standard Deviation)
 44.95  (12.38)   46.06  (12.82)   44.38  (10.60)   44.73  (11.89)   44.94  (11.92) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female   145   149   155   451   900 
Male   86   81   85   176   428 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
         
Hispanic or Latino   9   7   7   28   51 
Not Hispanic or Latino   181   172   188   520   1061 
Unknown or Not Reported   41   51   45   79   216 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
         
American Indian or Alaska Native   0   0   0   2   2 
Asian   47   45   56   121   269 
Native Hawaiian or Other Pacific Islander   0   0   0   0   0 
Black or African American   14   14   19   65   112 
White   164   170   164   429   927 
More than one race   5   1   0   9   15 
Unknown or Not Reported   1   0   1   1   3 
Region of Enrollment 
[Units: Participants]
Count of Participants
         
United States   73   76   74   318   541 
Poland   46   52   51   63   212 
Ukraine   33   29   29   36   127 
Russia   6   6   6   15   33 
South Africa   10   9   10   44   73 
Latvia   16   14   17   34   81 
Japan   47   44   53   117   261 


  Outcome Measures

1.  Primary:   Change From Randomization to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score   [ Time Frame: Randomization, 8 weeks ]

2.  Secondary:   Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Scale   [ Time Frame: Randomization, 8 weeks ]

3.  Secondary:   Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Impact Subscale Score   [ Time Frame: Randomization, 8 weeks ]

4.  Secondary:   Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 up to Week 8   [ Time Frame: Randomization up to 8 weeks ]

5.  Secondary:   Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 for at Least 2 Consecutive Measurements, Including the Participant's Last Measurement   [ Time Frame: Randomization up to 8 weeks ]

6.  Secondary:   Change From Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score   [ Time Frame: Randomization, 8 weeks ]

7.  Secondary:   Percentage of Participants Who Have a Greater Than or Equal to 50 Percent Improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization up to Week 8   [ Time Frame: Randomization up to 8 weeks ]

8.  Secondary:   Change From Randomization to Week 8 in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score   [ Time Frame: Randomization, 8 weeks ]

9.  Secondary:   Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items   [ Time Frame: Randomization, 8 weeks ]

10.  Secondary:   Change From Randomization to Week 8 in Clinical Global Impressions of Severity (CGI-S)   [ Time Frame: Randomization, 8 weeks ]

11.  Secondary:   Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Average Score and Experience Subscale Score   [ Time Frame: Randomization, 8 weeks ]

12.  Secondary:   Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items   [ Time Frame: Randomization, 8 weeks ]

13.  Secondary:   Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)   [ Time Frame: Randomization, 8 weeks ]

14.  Secondary:   Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D)   [ Time Frame: Randomization, 8 weeks ]

15.  Secondary:   Percentage of Treatment Emergent (TE) Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)   [ Time Frame: Randomization through 8 weeks ]

16.  Secondary:   Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale   [ Time Frame: Randomization, 8 weeks ]

17.  Secondary:   Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)   [ Time Frame: Randomization, 8 weeks ]

18.  Secondary:   The Percentage of Participants Experiencing Treatment-Emergent Adverse Events as a Function of CYP2D6 Phenotype   [ Time Frame: Through 8 weeks ]

19.  Secondary:   Change From Randomization to Week 8 in Blood Pressure (BP)   [ Time Frame: Randomization, 8 weeks ]

20.  Secondary:   Change From Randomization to Week 8 in Pulse Rate   [ Time Frame: Randomization, 8 weeks ]

21.  Secondary:   Pharmacokinetics: Plasma Concentrations of LY2216684   [ Time Frame: 1 week, 4 weeks, and 8 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01173601     History of Changes
Other Study ID Numbers: 11316
H9P-MC-LNBM ( Other Identifier: Eli Lilly and Company )
First Submitted: July 29, 2010
First Posted: August 2, 2010
Results First Submitted: February 17, 2018
Results First Posted: April 17, 2018
Last Update Posted: April 17, 2018