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  
Number of Participants  
[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)  
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 [2]
[units: participants]
         
< 4 drinks per day     22     34     33     25     114  
>= 4 drinks per day     0     0     0     0     0  
Does Participant Consume Caffeine?  
[units: participants]
         
Yes     77     84     83     81     325  
No     22     27     23     30     102  
Missing     16     17     18     12     63  
[1] BMI is calculated using the weight collected at the first screening visit: BMI=weight(kg)/[height(m)]^2.
[2] Only participants with drinking status Current Drinker are accounted for: N=22, 34, 33, 25 in each treatment arm, respectively.



  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)