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Efficacy and Safety of Ramelteon Sublingual in Adult Patients With Acute Depressive Episodes Associated With Bipolar I Disorder

This study has been terminated.
(Business Decision; No Safety Concerns)
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01467700
First received: November 4, 2011
Last updated: April 8, 2016
Last verified: April 2016
Results First Received: April 8, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Acute Depressive Episode
Interventions: Drug: Ramelteon SL
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 98 investigative sites in Argentina, Chile, Colombia, Mexico and the United States 12 December 2011 (first participant signed the informed consent form) to 10 March 2015.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a diagnosis of acute depressive episode were enrolled equally in 1 of 4 treatment groups, once a day placebo, ramelteon [TAK-375 SL (sublingual)] 0.1 mg, 0.4 mg or 0.8 mg.

Reporting Groups
  Description
Placebo Ramelteon SL placebo-matching, tablets, sublingual (SL) [dissolved under the tongue], once daily, every night at bedtime for up to 8 weeks.
Ramelteon SL 0.1 mg Ramelteon SL 0.1 mg, tablets, SL, once daily (QD), every night at bedtime for up to 8 weeks.
Ramelteon SL 0.4 mg Ramelteon SL 0.4 mg, tablets, SL, once daily, every night at bedtime for up to 8 weeks.
Ramelteon SL 0.8 mg Ramelteon SL 0.8 mg tablets, SL, once daily, every night at bedtime for up to 8 weeks.

Participant Flow:   Overall Study
    Placebo   Ramelteon SL 0.1 mg   Ramelteon SL 0.4 mg   Ramelteon SL 0.8 mg
STARTED   115   128   124   123 
Safety Set - Received Treatment   115   127   124   123 
COMPLETED   86   100   97   96 
NOT COMPLETED   29   28   27   27 
Pretreatment Event or Adverse Event                6                4                2                3 
Major Protocol Deviation                3                3                2                3 
Lost to Follow-up                6                5                2                3 
Voluntary Withdrawal                5                7                6                2 
Study Termination                6                5                10                7 
Pregnancy                0                1                1                0 
Lack of Efficacy                2                0                2                1 
Reason not Specified                1                3                2                8 



  Baseline Characteristics
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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.
All randomized participants.

Reporting Groups
  Description
Placebo Ramelteon SL placebo-matching, tablets, sublingual (SL) [dissolved under the tongue], once daily, every night at bedtime for up to 8 weeks.
Ramelteon SL 0.1 mg Ramelteon SL 0.1 mg, tablets, SL, once daily (QD), every night at bedtime for up to 8 weeks.
Ramelteon SL 0.4 mg Ramelteon SL 0.4 mg, tablets, SL, once daily, every night at bedtime for up to 8 weeks.
Ramelteon SL 0.8 mg Ramelteon SL 0.8 mg tablets, SL, once daily, every night at bedtime for up to 8 weeks.
Total Total of all reporting groups

Baseline Measures
   Placebo   Ramelteon SL 0.1 mg   Ramelteon SL 0.4 mg   Ramelteon SL 0.8 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 115   128   124   123   490 
Age 
[Units: Years]
Mean (Standard Deviation)
 44.95  (10.867)   43.01  (11.998)   42.96  (13.211)   43.97  (10.243)   43.69  (11.646) 
Age, Customized 
[Units: Participants]
         
<=50 Years   85   92   88   97   362 
>50 Years   30   36   36   26   128 
Age, Customized 
[Units: Participants]
         
<=65 years   111   126   119   121   477 
>65 Years   4   2   5   2   13 
Gender 
[Units: Participants]
         
Female   74   71   78   69   292 
Male   41   57   46   54   198 
Race/Ethnicity, Customized 
[Units: Participants]
         
Hispanic or Latino   36   38   35   37   146 
Non-Hispanic and Non-Latino   79   90   89   86   344 
Race/Ethnicity, Customized 
[Units: Participants]
         
White   76   81   85   79   321 
Black   29   42   32   38   141 
Asian   3   0   2   0   5 
American Indian or Alaska Native   5   3   0   4   12 
Native Hawaiian or Other Pacific Islander   1   0   1   1   3 
Multiple   1   2   4   1   8 
Region of Enrollment 
[Units: Participants]
         
United States   85   97   95   94   371 
Argentina   12   11   11   11   45 
Chile   5   5   6   3   19 
Colombia   3   3   1   3   10 
Mexico   10   12   11   12   45 
Height 
[Units: Cm]
Mean (Standard Deviation)
 166.93  (10.345)   169.00  (9.937)   167.22  (9.677)   168.15  (10.590)   167.85  (10.139) 
Weight 
[Units: Kg]
Mean (Standard Deviation)
 85.44  (20.034)   87.58  (21.555)   85.09  (20.873)   86.69  (21.535)   86.22  (20.989) 
Body Mass Index (BMI) [1] 
[Units: Kg/m^2]
Mean (Standard Deviation)
 30.62  (6.778)   30.63  (7.254)   30.37  (6.808)   30.61  (6.825)   30.56  (6.904) 
[1] BMI is calculated using the weight collected at the first screening visit: BMI=weight(kg)/[height(m)]^2.
Smoking Classification 
[Units: Participants]
         
Participant Has Never Smoked   47   55   49   45   196 
Participant is a Current Smoker   50   58   58   58   224 
Participant is an Ex-smoker   18   15   17   20   70 
Participant Drinking Status 
[Units: Participants]
         
Has Never Drunk   52   41   45   49   187 
Ex-Drinker   25   36   28   37   126 
Current Drinker   22   34   33   25   114 
Missing   16   17   18   12   63 
If Drinker, Amount Consumed [1] 
[Units: Participants]
         
< 4 drinks per day   22   34   33   25   114 
>= 4 drinks per day   0   0   0   0   0 
[1] Only participants with drinking status Current Drinker are accounted for: N=22, 34, 33, 25 in each treatment arm, respectively.
Does Participant Consume Caffeine? 
[Units: Participants]
         
Yes   77   84   83   81   325 
No   22   27   23   30   102 
Missing   16   17   18   12   63 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6   [ Time Frame: Baseline and Week 6 ]

2.  Secondary:   Change From Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) Short Form Total Score at Week 6   [ Time Frame: Baseline and Week 6 ]

3.  Secondary:   Percentage of Participants With MADRS Response at Week 6, With Response Defined as a ≥ 50% Decrease in the MADRS Total Score From Baseline   [ Time Frame: Baseline and Week 6 ]

4.  Secondary:   Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 6   [ Time Frame: Baseline and Week 6 ]

5.  Secondary:   Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 6   [ Time Frame: 6 Weeks ]

6.  Secondary:   Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) at Week 6   [ Time Frame: Baseline and Week 6 ]

7.  Secondary:   Percentage of Participants With MADRS Remission at Week 6, With Remission Defined as a MADRS Total Score ≤10   [ Time Frame: Week 6 ]

8.  Secondary:   Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self-Rated16 (QIDS-SR16) Total Score at Week 6   [ Time Frame: Baseline and Week 6 ]

9.  Secondary:   Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 6   [ Time Frame: Baseline and Week 6 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Director, Clinical Science
Organization: Takeda
phone: +1-877-825-3327
e-mail: trialdisclosures@takeda.com



Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01467700     History of Changes
Other Study ID Numbers: TAK-375SL_201
U1111-1122-7380 ( Registry Identifier: WHO )
Study First Received: November 4, 2011
Results First Received: April 8, 2016
Last Updated: April 8, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Chile: Ministry of Health
Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA)
Mexico: Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)