Facilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia

This study has been completed.

Study NCT00492232 Information provided by Takeda Global Research & Development Center, Inc.

First Received on June 25, 2007. Last Updated on July 13, 2010 History of Changes

Results First Received: May 28, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Chronic Insomnia
Interventions:	Drug: Ramelteon and zolpidem Drug: Placebo and zolpidem

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 38 investigative sites in the United States from 26 April 2007 to 28 May 2008.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects completed a 4-week single-blind placebo run-in period prior to randomization in the double-blind treatment period (DBTP). During this time they took placebo-matching tablets once-daily (QD) with concomitant current zolpidem therapy. Subjects used a daily subject diary to record zolpidem dose reduction, daily activities, and sleep quality.

Reporting Groups

	Description
Ramelteon 8 mg QD	Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Placebo QD	Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.

Participant Flow for 3 periods

Period 1: Placebo Run-in

	Ramelteon 8 mg QD	Placebo QD
STARTED	0	205 ^[1]
COMPLETED	0	135 ^[2]
NOT COMPLETED	0	70
Adverse Event	0	2
Protocol Violation	0	3
Lost to Follow-up	0	3
Withdrawal by Subject	0	8
Pregnancy	0	1
Entrance criteria not met	0	45
Other	0	6
Missing	0	2

[1]	All subjects received placebo in the placebo run-in period.
[2]	These subjects successfully completed the placebo run-in period and were randomized to the DBTP.

Period 2: Double-Blind Treatment

	Ramelteon 8 mg QD	Placebo QD
STARTED	65	70
COMPLETED	47	45
NOT COMPLETED	18	25
Adverse Event	1	2
Protocol Violation	3	7
Lost to Follow-up	2	3
Withdrawal by Subject	4	8
Lack of Efficacy	1	0
Other	6	5
Randomized not treated	1	0

Period 3: Open-Label Treatment

	Ramelteon 8 mg QD	Placebo QD
STARTED	89 ^[1]	0 ^[2]
COMPLETED	88	0
NOT COMPLETED	1	0
Withdrawal by Subject	1	0

[1]	In the previous DBTP, 45 and 44 subjects were randomized to ramelteon and placebo, respectively.
[2]	All subjects received ramelteon in the OLTP.

Baseline Characteristics

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Reporting Groups

	Description
Ramelteon 8 mg QD	Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Placebo QD	Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.

Baseline Measures

	Ramelteon 8 mg QD	Placebo QD	Total
Number of Participants [units: participants]	65	70	135
Age [units: years] Mean ± Standard Deviation	51.5 ± 13.45	47.0 ± 12.98	49.2 ± 13.35
Gender [units: Subjects]
Female	42	49	91
Male	23	21	44
Race/Ethnicity, Customized [units: Subjects]
Asian	1	1	2
Black or African American	5	9	14
White	59	59	118
Multiracial	0	1	1
Ethnicity (NIH/OMB) [units: Subjects]
Hispanic or Latino	10	9	19
Not Hispanic or Latino	55	61	116
Unknown or Not Reported	0	0	0
Baseline average total daily zolpidem dosage [units: subjects]
≤10 mg	56	60	116
>10 mg	8	10	18
Information not available	1	0	1
Use of pharmacological assistance to sleep ^[1] [units: subjects]
4 nights per week	8	9	17
>4 nights per week	57	61	118
Weekly frequency zolpidem consumption ^[2] [units: subjects]
0-3 nights per week	0	0	0
4 nights per week	2	1	3
5 nights per week	8	9	17
6 nights per week	8	7	15
7 nights per week	46	53	99
Information not available	1	0	1
Baseline weekly zolpidem dosage ^[3] [units: Dosage (mg)] Mean ± Standard Deviation	68.7 ± 17.71	70.3 ± 20.37	69.5 ± 19.09
Weekly frequency zolpidem consumption ^[4] [units: nights per week] Mean ± Standard Deviation	6.53 ± 0.835	6.60 ± 0.769	6.57 ± 0.799

[1]	Randomized subjects responded to the question, "How often per week do you use pharmacological assistance to sleep?" 4=4 nights/week; >4=5-7 nights/week.
[2]	The average number of nights per week subjects took zolpidem was calculated.
[3]	Baseline for the weekly zolpidem dosage was calculated as the total amount zolpidem intake recorded by a subject during placebo run-in, divided by the number of days in the period, multiplied by 7. Ramelteon 8 mg n=64; Placebo n=70.
[4]	Average number of nights per week randomized subjects used zolpidem. Ramelteon 8 mg n=64; Placebo n=70.

Outcome Measures

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1. Primary:

Percentage of Participants Who Discontinued Zolpidem Therapy [ Time Frame: Week 10 ]

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2. Secondary:

Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2 [ Time Frame: Baseline and Weeks 1-2 ]

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3. Secondary:

Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4 [ Time Frame: Baseline and Weeks 3-4 ]

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4. Secondary:

Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6 [ Time Frame: Baseline and Weeks 5-6 ]

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5. Secondary:

Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8 [ Time Frame: Baseline and Weeks 7-8 ]

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6. Secondary:

Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10 [ Time Frame: Baseline and Weeks 9-10 ]

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7. Secondary:

Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-2 [ Time Frame: Baseline and Weeks 1-2 ]

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8. Secondary:

Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4 [ Time Frame: Weeks 3-4 ]

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9. Secondary:

Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6 [ Time Frame: Weeks 5-6 ]

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10. Secondary:

Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8 [ Time Frame: Baseline and Weeks 7-8 ]

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11. Secondary:

Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10 [ Time Frame: Baseline and Weeks 9-10 ]

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12. Secondary:

Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation [ Time Frame: Weeks 1-10 ]

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13. Secondary:

Participants Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period [ Time Frame: Baseline and Week 10 ]

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14. Secondary:

Participants Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period [ Time Frame: Baseline and Weeks 1-10 ]

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period up to 150 days to permit actions necessary to preserve sponsor's intellectual property; can request changes to the results communication only for the purpose of removing non study related information that is proprietary and confidential to sponsor; can require delay of a results communication until the study has been completed at all participating sites.

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
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Results Point of Contact:

Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research and 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:	NCT00492232 History of Changes
Other Study ID Numbers:	01-06-TL-375-071, U1111-1114-3262
Study First Received:	June 25, 2007
Results First Received:	May 28, 2009
Last Updated:	July 13, 2010
Health Authority:	United States: Food and Drug Administration