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Safety and Efficacy Study of Ramelteon in Subjects With Chronic Insomnia

This study has been completed.
Sponsor:
Information provided by:
Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:
NCT00756002
First received: September 17, 2008
Last updated: May 31, 2010
Last verified: May 2010
History of Changes
Results First Received: April 3, 2009  
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: Sleep Initiation and Maintenance Disorders
Interventions: Drug: Ramelteon
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
Subjects were enrolled at 19 sites in Europe and Russia from 21 August 2007 to 28 March 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Sleep quality was assessed by postsleep questionnaires during a 21-day placebo run-in. Subjects were enrolled in Ramelteon or Placebo once-daily (QD) treatment group.

488 subjects entered placebo Run-in Period. 229 failed randomization criteria for entry into double-blind study medication phase of the study. 259 were randomized into the study.

Reporting Groups
  Description
Placebo QD Oral Placebo was self-administered once-daily, 30 minutes prior to bedtime. The study medication consisted of identical film-coated pale orange-yellow tablets.
Ramelteon 4 mg QD Ramelteon 4 mg tablets, self-administered once-daily, 30 minutes prior to bedtime. Study medication consisted of identical film-coated pale orange-yellow tablets.

Participant Flow for 3 periods

 Period 1:   Placebo Run-in
    Placebo QD     Ramelteon 4 mg QD  
STARTED     488     0  
COMPLETED     259     0  
NOT COMPLETED     229     0  

Period 2:   Double-Blind Treatment Period
    Placebo QD     Ramelteon 4 mg QD  
STARTED     129     130  
COMPLETED     114     115  
NOT COMPLETED     15     15  
Lack of Efficacy                 1                 1  
Lost to Follow-up                 0                 1  
Withdrawal by Subject                 6                 6  
Protocol Violation                 6                 5  
Not Specified                 2                 2  

Period 3:   Placebo Run-out
    Placebo QD     Ramelteon 4 mg QD  
STARTED     114     0  
COMPLETED     114     0  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Reporting Groups
  Description
Placebo QD Oral Placebo was self-administered once-daily, 30 minutes prior to bedtime. The study medication consisted of identical film-coated pale orange-yellow tablets.
Ramelteon 4 mg QD Ramelteon 4 mg tablets, self-administered once-daily, 30 minutes prior to bedtime. Study medication consisted of identical film-coated pale orange-yellow tablets.
Total Total of all reporting groups

Baseline Measures
    Placebo QD     Ramelteon 4 mg QD     Total  
Number of Participants  
[units: participants]
 		  129     130     259  
Age  
[units: years]
Mean ± Standard Deviation 		  42.3  ± 12.28     41.7  ± 11.85     42.0  ± 12.05  
Gender  
[units: participants]
 		     
Female     55     53     108  
Male     74     77     151  
Race/Ethnicity, Customized  
[units: participants]
 		     
Asian     1     0     1  
Black or African American     0     1     1  
White     128     129     257  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Mean Latency to Persistent Sleep Via Polysomnography (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 1

2.  Secondary:   Mean Latency to Persistent Sleep Via Polysomnography (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Show Outcome Measure 2

3.  Secondary:   Mean Latency to Persistent Sleep Via Polysomnography (Nights 29-30).   [ Time Frame: Nights 29-30 ]
  Show Outcome Measure 3

4.  Secondary:   Subjective Sleep Latency, Per Post-sleep Questionnaire (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 4

5.  Secondary:   Subjective Sleep Latency, Per Post-sleep Questionnaire (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Show Outcome Measure 5

6.  Secondary:   Subjective Sleep Latency, Per Post-sleep Questionnaire (Nights 29-30).   [ Time Frame: Nights 29-30 ]
  Show Outcome Measure 6

7.  Secondary:   Subjective Sleep Latency, Per Post-sleep Questionnaire (Week 2).   [ Time Frame: Week 2 ]
  Show Outcome Measure 7

8.  Secondary:   Subjective Sleep Latency, Per Post-sleep Questionnaire (Week 4).   [ Time Frame: Week 4 ]
  Show Outcome Measure 8

9.  Secondary:   Subjective Sleep Latency, Per Post-sleep Questionnaire (Week 5).   [ Time Frame: Week 5 ]
  Show Outcome Measure 9

10.  Secondary:   Total Sleep Time, Per Polysomnography (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 10

11.  Secondary:   Total Sleep Time, Per Polysomnography (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Show Outcome Measure 11

12.  Secondary:   Total Sleep Time, Per Polysomnography (Nights 29-30).   [ Time Frame: Nights 29-30 ]
  Show Outcome Measure 12

13.  Secondary:   Subjective Total Sleep Time, Per Post-sleep Questionnaire (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 13

14.  Secondary:   Subjective Total Sleep Time, Per Post-sleep Questionnaire (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Hide Outcome Measure 14

Measure Type Secondary
Measure Title Subjective Total Sleep Time, Per Post-sleep Questionnaire (Nights 15-16).
Measure Description Subjects answered a Post-Sleep Questionnaire in the sleep lab the morning following overnight Polysomnography. Subjective Total Sleep Time measured the average of the 2 mornings after each overnight Polysomnography Visit.
Time Frame Nights 15-16  
Safety Issue No  

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.
The FAS population consisted of all subjects who were randomized and received at least 1 dose of double-blind study medication. Subjects were analyzed according to the treatment they were randomized to receive. The analysis was performed using the FAS and LOCF data.

Reporting Groups
  Description
Placebo QD Oral Placebo was self-administered once-daily, 30 minutes prior to bedtime. The study medication consisted of identical film-coated pale orange-yellow tablets.
Ramelteon 4 mg QD Ramelteon 4 mg tablets, self-administered once-daily, 30 minutes prior to bedtime. Study medication consisted of identical film-coated pale orange-yellow tablets.

Measured Values
    Placebo QD     Ramelteon 4 mg QD  
Number of Participants Analyzed  
[units: participants]
 		  128     130  
Subjective Total Sleep Time, Per Post-sleep Questionnaire (Nights 15-16).  
[units: minutes]
Least Squares Mean ± Standard Error 		  332.6  ± 4.63     345.9  ± 4.57  


Statistical Analysis 1 for Subjective Total Sleep Time, Per Post-sleep Questionnaire (Nights 15-16).
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.043
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  LS means from ANCOVA model with effects for treatment & pooled center, with Baseline as a covariate. P-values from t-tests of the ANCOVA model for the overall treatment comparison. Statistical significance was determined at the 0.05 level.



15.  Secondary:   Subjective Total Sleep Time, Per Post-sleep Questionnaire (Nights 29-30).   [ Time Frame: Nights 29 -30 ]
  Show Outcome Measure 15

16.  Secondary:   Subjective Total Sleep Time, Per Post-sleep Questionnaire (Week 2).   [ Time Frame: Week 2 ]
  Show Outcome Measure 16

17.  Secondary:   Subjective Total Sleep Time, Per Post-sleep Questionnaire (Week 4).   [ Time Frame: Week 4 ]
  Show Outcome Measure 17

18.  Secondary:   Subjective Total Sleep Time, Per Post-sleep Questionnaire (Week 5).   [ Time Frame: Week 5 ]
  Show Outcome Measure 18

19.  Secondary:   Sleep Efficiency, Per Polysomnography (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 19

20.  Secondary:   Sleep Efficiency, Per Polysomnography (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Show Outcome Measure 20

21.  Secondary:   Sleep Efficiency, Per Polysomnography (Nights 29-30).   [ Time Frame: Nights 29-30 ]
  Show Outcome Measure 21

22.  Secondary:   Subjective Sleep Quality, Per Post-sleep Questionnaire (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 22

23.  Secondary:   Subjective Sleep Quality, Per Post-sleep Questionnaire (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Show Outcome Measure 23

24.  Secondary:   Subjective Sleep Quality, Per Post-sleep Questionnaire (Nights 29-30).   [ Time Frame: Nights 29-30 ]
  Show Outcome Measure 24

25.  Secondary:   Subjective Sleep Quality, Per Post-sleep Questionnaire (Week 2).   [ Time Frame: Week 2 ]
  Show Outcome Measure 25

26.  Secondary:   Subjective Sleep Quality, Per Post-sleep Questionnaire (Week 4).   [ Time Frame: Week 4 ]
  Show Outcome Measure 26

27.  Secondary:   Subjective Sleep Quality, Per Post-sleep Questionnaire (Week 5).   [ Time Frame: Week 5 ]
  Show Outcome Measure 27

28.  Secondary:   Wake Time After Sleep Onset, Per Polysomnography (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 28

29.  Secondary:   Wake Time After Sleep Onset, Per Polysomnography (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Show Outcome Measure 29

30.  Secondary:   Wake Time After Sleep Onset, Per Polysomnography (Nights 29-30).   [ Time Frame: Nights 29-30 ]
  Show Outcome Measure 30

31.  Secondary:   Subjective Wake Time After Sleep Onset, Per Post-sleep Questionnaire (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 31

32.  Secondary:   Subjective Wake Time After Sleep Onset, Per Post-sleep Questionnaire (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Show Outcome Measure 32

33.  Secondary:   Subjective Wake Time After Sleep Onset, Per Post-sleep Questionnaire (Nights 29-30).   [ Time Frame: Nights 29-30 ]
  Show Outcome Measure 33

34.  Secondary:   Subjective Wake Time After Sleep Onset, Per Post-sleep Questionnaire (Week 2).   [ Time Frame: Week 2 ]
  Show Outcome Measure 34

35.  Secondary:   Subjective Wake Time After Sleep Onset, Per Post-sleep Questionnaire (Week 4).   [ Time Frame: Week 4 ]
  Show Outcome Measure 35

36.  Secondary:   Subjective Wake Time After Sleep Onset, Per Post-sleep Questionnaire (Week 5).   [ Time Frame: Week 5 ]
  Show Outcome Measure 36

37.  Secondary:   Number of Awakenings After Persistent Sleep, Per Polysomnography (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 37

38.  Secondary:   Number of Awakenings After Persistent Sleep, Per Polysomnography (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Show Outcome Measure 38

39.  Secondary:   Number of Awakenings After Persistent Sleep, Per Polysomnography (Nights 29-30).   [ Time Frame: Nights 29-30 ]
  Show Outcome Measure 39

40.  Secondary:   Subjective Number of Awakenings, Per Post-sleep Questionnaire (Nights 1-2).   [ Time Frame: Nights 1-2 ]
  Show Outcome Measure 40

41.  Secondary:   Subjective Number of Awakenings, Per Post-sleep Questionnaire (Nights 15-16).   [ Time Frame: Nights 15-16 ]
  Show Outcome Measure 41

42.  Secondary:   Subjective Number of Awakenings, Per Post-sleep Questionnaire (Nights 29-30).   [ Time Frame: Nights 29-30 ]
  Show Outcome Measure 42

43.  Secondary:   Subjective Number of Awakenings, Per Post-sleep Questionnaire (Week 2).   [ Time Frame: Week 2 ]
  Show Outcome Measure 43

44.  Secondary:   Subjective Number of Awakenings, Per Post-sleep Questionnaire (Week 4).   [ Time Frame: Week 4 ]
  Show Outcome Measure 44

45.  Secondary:   Subjective Number of Awakenings, Per Post-sleep Questionnaire (Week 5).   [ Time Frame: Week 5 ]
  Show Outcome Measure 45


  Serious Adverse Events
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  Other Adverse Events
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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.


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.  


Results Point of Contact:  
Name/Title: Sr VP, Clinical Science
Organization: Takeda Global Research & Development Center, Inc.
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com


No publications provided


Responsible Party: Sr VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00756002     History of Changes
Other Study ID Numbers: 01-06-TL-375-081, 2007-000403-15, U1111-1115-2084
Study First Received: September 17, 2008
Results First Received: April 3, 2009
Last Updated: May 31, 2010
Health Authority: European Union: European Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices