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A Study of Flexible or Fixed Dose LY2216684 as Adjunctive Treatment for Participants With Major Depressive Disorder Who Have Had a Partial Response to Selective Serotonin Reuptake Inhibitor (SSRI) Treatment

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ClinicalTrials.gov Identifier: NCT01187407
Recruitment Status : Completed
First Posted : August 24, 2010
Results First Posted : April 24, 2018
Last Update Posted : April 24, 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 (MDD)
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 of the study was a double-blind Confirmation Phase during which participants continued to receive their SSRI with adjunctive placebo. If randomization criteria were met, participants were randomized to adjunctive LY2216684 or adjunctive 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 (QD) for 3 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
12 or 18 mg LY2216684 + SSRI (Randomized Participants) LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, QD for 8 weeks, adjunctive to an SSRI
6 mg LY2216684 + SSRI (Randomized Participants) LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
Placebo + SSRI (Randomized Participants) Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
Placebo + SSRI (Non-randomized Participants) Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI

Participant Flow for 2 periods

Period 1:   Confirmation (CF) Phase, 3 Weeks
    Placebo + SSRI (Pre-randomized Participants)   12 or 18 mg LY2216684 + SSRI (Randomized Participants)   6 mg LY2216684 + SSRI (Randomized Participants)   Placebo + SSRI (Randomized Participants)   Placebo + SSRI (Non-randomized Participants)
STARTED   1480   0   0   0   0 
Entered Discontinuation (DC) Phase   25 [1]   0   0   0   0 
COMPLETED   1390 [2]   0   0   0   0 
NOT COMPLETED   90   0   0   0   0 
Adverse Event                29                0                0                0                0 
Lack of Efficacy                4                0                0                0                0 
Lost to Follow-up                9                0                0                0                0 
Physician Decision                2                0                0                0                0 
Protocol Violation                13                0                0                0                0 
Withdrawal by Subject                29                0                0                0                0 
Sponsor Decision                4                0                0                0                0 
[1] Participants who discontinued the CF Phase early had the option to enter the DC Phase.
[2] Participants who completed the CF Phase entered the Adjunctive Treatment (AT) Phase.

Period 2:   Adjunctive Treatment (AT) Phase, 8 Weeks
    Placebo + SSRI (Pre-randomized Participants)   12 or 18 mg LY2216684 + SSRI (Randomized Participants)   6 mg LY2216684 + SSRI (Randomized Participants)   Placebo + SSRI (Randomized Participants)   Placebo + SSRI (Non-randomized Participants)
STARTED   0   232   226   231   701 
Entered Discontinuation (DC) Phase   0   212 [1]   215 [1]   220 [1]   660 [1] 
COMPLETED   0   196   191   202   626 
NOT COMPLETED   0   36   35   29   75 
Adverse Event                0                13                6                5                12 
Lack of Efficacy                0                3                8                5                13 
Lost to Follow-up                0                3                5                2                9 
Physician Decision                0                0                0                1                2 
Protocol Violation                0                6                5                3                10 
Withdrawal by Subject                0                9                9                11                22 
Sponsor Decision                0                2                2                2                7 
[1] Participants who completed the AT Phase or discontinued early had the option to enter the 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 (CF) 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 or 18 mg LY2216684 + SSRI (Randomized Participants) LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
6 mg LY2216684 + SSRI (Randomized Participants) LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
Placebo + SSRI (Randomized Participants) Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
Placebo + SSRI (Non-randomized Participants) Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
Total Total of all reporting groups

Baseline Measures
   12 or 18 mg LY2216684 + SSRI (Randomized Participants)   6 mg LY2216684 + SSRI (Randomized Participants)   Placebo + SSRI (Randomized Participants)   Placebo + SSRI (Non-randomized Participants)   Total 
Overall Participants Analyzed 
[Units: Participants]
 232   226   231   701   1390 
Age 
[Units: Years]
Mean (Standard Deviation)
 46.63  (12.00)   47.06  (12.76)   47.30  (12.10)   46.35  (12.42)   46.67  (12.35) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female      149  64.2%      153  67.7%      156  67.5%      465  66.3%      923  66.4% 
Male      83  35.8%      73  32.3%      75  32.5%      236  33.7%      467  33.6% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
         
Hispanic or Latino      11   4.7%      9   4.0%      14   6.1%      49   7.0%      83   6.0% 
Not Hispanic or Latino      183  78.9%      181  80.1%      178  77.1%      562  80.2%      1104  79.4% 
Unknown or Not Reported      38  16.4%      36  15.9%      39  16.9%      90  12.8%      203  14.6% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
         
American Indian or Alaska Native      1   0.4%      0   0.0%      3   1.3%      4   0.6%      8   0.6% 
Asian      21   9.1%      26  11.5%      20   8.7%      54   7.7%      121   8.7% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American      16   6.9%      25  11.1%      18   7.8%      63   9.0%      122   8.8% 
White      192  82.8%      173  76.5%      186  80.5%      572  81.6%      1123  80.8% 
More than one race      2   0.9%      2   0.9%      3   1.3%      8   1.1%      15   1.1% 
Unknown or Not Reported      0   0.0%      0   0.0%      1   0.4%      0   0.0%      1   0.1% 
Region of Enrollment 
[Units: Participants]
Count of Participants
         
United States   103   98   104   377   682 
Czechia   44   44   46   119   253 
Slovakia   33   35   34   39   141 
Finland   18   12   17   61   108 
Croatia   9   10   7   26   52 
Japan   20   23   19   53   115 
Hungary   2   2   1   3   8 
Romania   3   2   3   23   31 


  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 the Sheehan Disability Scale (SDS) Global Functional Impairment Score   [ Time Frame: Randomization, 8 weeks ]

3.  Secondary:   Change From Randomization to Week 8 in the 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 to 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 the 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 the 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 The 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 Participants With 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 the Arizona Sexual Experiences (ASEX) Scale   [ Time Frame: Randomization, 8 weeks ]

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

18.  Secondary:   Change From Randomization to Week 8 in Blood Pressure   [ Time Frame: Randomization, 8 weeks ]

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

20.  Secondary:   Pharmacokinetics: Plasma Concentrations of LY2216684   [ Time Frame: Pre-randomization, 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: 800-545-597


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

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01187407     History of Changes
Other Study ID Numbers: 12182
H9P-MC-LNBQ ( Other Identifier: Eli Lilly and Company )
First Submitted: August 20, 2010
First Posted: August 24, 2010
Results First Submitted: February 17, 2018
Results First Posted: April 24, 2018
Last Update Posted: April 24, 2018