A Duloxetine Dosing Strategy Study in Korean Patients With Major Depressive Disorder

This study has been completed.

Sponsor:

Collaborator:

Boehringer Ingelheim Pharmaceuticals

Information provided by (Responsible Party):

Eli Lilly and Company

ClinicalTrials.gov Identifier:

NCT00960986

First received: August 17, 2009

Last updated: March 23, 2012

Last verified: March 2012

History of Changes

Results First Received: January 17, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Major Depressive Disorder (MDD)
Intervention:	Drug: Duloxetine hydrochloride

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
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Period 1 was a 3- to 30-day screening and washout period; Period 2 (Week 0-1) was a 1-week initial dosing period (randomization to duloxetine 30 mg with food, 30 mg without food, 60 mg with food, or 60 mg without food); Period 3 (Week 1-8) was a 7-week therapy period (treatment switched to duloxetine 60 mg once daily (QD) until study end.

Reporting Groups

	Description
Duloxetine 60 mg With Food	Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
Duloxetine 60 mg Without Food	Duloxetine 60 mg capsule po QD without food for 8 weeks
Duloxetine 30 mg With Food	Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
Duloxetine 30 mg Without Food	Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks

Participant Flow for 3 periods

Period 1: Period 1 (Screening and Washout)

	Duloxetine 60 mg With Food	Duloxetine 60 mg Without Food	Duloxetine 30 mg With Food	Duloxetine 30 mg Without Food
STARTED	59	63	63	64
COMPLETED	56	59	59	61
NOT COMPLETED	3	4	4	3
Adverse Event	1	2	1	1
Lost to Follow-up	0	0	2	1
Protocol Violation	1	0	0	0
Withdrawal by Subject	1	2	1	1

Period 2: Period 2 (1-week Initial Dosing Period)

	Duloxetine 60 mg With Food	Duloxetine 60 mg Without Food	Duloxetine 30 mg With Food	Duloxetine 30 mg Without Food
STARTED	56	59	59	61
COMPLETED	56	59	59	61
NOT COMPLETED	0	0	0	0

Period 3: Period 3 (7-week Therapy Period)

	Duloxetine 60 mg With Food	Duloxetine 60 mg Without Food	Duloxetine 30 mg With Food	Duloxetine 30 mg Without Food
STARTED	56	59	59	61
COMPLETED	26	36	39	36
NOT COMPLETED	30	23	20	25
Adverse Event	17	15	10	12
Death	0	0	1	0
Lost to Follow-up	0	0	1	0
Protocol Violation	10	4	3	11
Withdrawal by Subject	2	2	4	2
Lack of Efficacy	1	2	1	0

Baseline Characteristics

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Reporting Groups

	Description
Duloxetine 60 mg With Food	Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
Duloxetine 60 mg Without Food	Duloxetine 60 mg capsule po QD without food for 8 weeks
Duloxetine 30 mg With Food	Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
Duloxetine 30 mg Without Food	Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
Total	Total of all reporting groups

Baseline Measures

	Duloxetine 60 mg With Food	Duloxetine 60 mg Without Food	Duloxetine 30 mg With Food	Duloxetine 30 mg Without Food	Total
Number of Participants [units: participants]	59	63	63	64	249
Age [units: years] Mean ( Inter-Quartile Range )	44.65 ( 31.58 to 53.73 )	47.90 ( 38.65 to 58.90 )	49.94 ( 40.04 to 62.24 )	44.65 ( 32.84 to 56.92 )	46.81 ( 34.78 to 59.25 )
Gender [units: participants]
Female	43	47	47	40	177
Male	16	16	16	24	72
Race/Ethnicity, Customized [units: participants]
Korean	59	63	63	64	249
Region of Enrollment [units: participants]
Korea, Republic of	59	63	63	64	249
Body Mass Index (BMI) ^[1] [units: kilogram per square meter (kg/m^2)] Mean ± Standard Deviation	24.56 ± 4.034	23.28 ± 3.133	23.06 ± 3.430	23.84 ± 3.612	23.67 ± 3.584
Previously diagnosed with major depressive disorder (MDD) [units: participants]	59	63	63	64	249
Duration since first major depressive disorder (MDD) episode [units: years] Median ( Inter-Quartile Range )	1.47 ( 0.52 to 4.29 )	2.65 ( 0.77 to 5.32 )	2.52 ( 0.48 to 9.12 )	1.29 ( 0.52 to 4.40 )	1.92 ( 0.54 to 5.55 )
Age at first major depressive disorder (MDD) episode [units: years] Mean ( Inter-Quartile Range )	41.21 ( 29.00 to 51.00 )	43.33 ( 34.67 to 53.00 )	43.86 ( 27.00 to 59.60 )	41.58 ( 29.00 to 54.00 )	42.52 ( 30.00 to 54.00 )
Number of previous MDD episodes/exacerbations in the last 24 months [units: number of episodes in last 24 months] Median ( Inter-Quartile Range )	1.0 ( 0.0 to 1.0 )	1.0 ( 0.0 to 1.0 )	1.0 ( 0.0 to 1.0 )	1.0 ( 0.0 to 1.0 )	1.0 ( 0.0 to 1.0 )
Received previous therapy for current episode [units: participants]
yes	18	25	18	26	87
no	41	38	45	38	162
17-item Hamilton Depression Rating Scale (HAMD-17) Total Score ^[2] [units: units on a scale] Mean ± Standard Deviation	21.0 ± 5.18	22.3 ± 5.69	22.9 ± 5.45	20.3 ± 5.23	21.6 ± 5.46
Clinical Global Impression of Severity (CGI-S) Score ^[3] [units: units on a scale] Mean ( Inter-Quartile Range )	4.4 ( 4.0 to 5.0 )	4.5 ( 4.0 to 5.0 )	4.7 ( 4.0 to 5.0 )	4.2 ( 4.0 to 5.0 )	4.4 ( 4.0 to 5.0 )
Association for Methodology and Documentation in Psychiatry (AMDP-5) Item 112 (Nausea) Score ^[4] [units: units on a scale] Mean ± Standard Deviation	0.3 ± 0.72	0.2 ± 0.59	0.2 ± 0.61	0.1 ± 0.38	0.2 ± 0.58

[1]	BMI measures the participant's body weight divided by the square of his or her height.
[2]	The HAMD-17 measured depression severity. Each item was evaluated and scored using either a 5-point scale (for example, absent; mild; moderate; severe; very severe) or a 3-point scale (for example, absent; mild; marked). The total score ranged from 0 (not at all depressed)-52 (severely depressed).
[3]	The CGI-S Rating Scale was a 7-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; or 7=extremely ill.
[4]	AMDP-5 Item 112 (nausea) measured nausea severity. The scores ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe.

Outcome Measures

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1. Primary:

Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) [ Time Frame: 1 week and 8 weeks ]

Show Outcome Measure 1

2. Secondary:

Mean Change From Baseline to 8-Week Endpoint in Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) [ Time Frame: Baseline, 8 weeks ]

Show Outcome Measure 2

3. Secondary:

Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score [ Time Frame: Baseline, 1 week and 8 weeks ]

Show Outcome Measure 3

4. Secondary:

Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score [ Time Frame: Baseline, 1 week, 8 weeks ]

Show Outcome Measure 4

5. Secondary:

Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score [ Time Frame: Baseline, 1 week, 8 weeks ]

Show Outcome Measure 5

6. Secondary:

Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale [ Time Frame: Baseline, 1 week, 8 weeks ]

Show Outcome Measure 6

7. Secondary:

Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale [ Time Frame: Baseline, 1 week, 8 weeks ]

Show Outcome Measure 7

8. Secondary:

Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale [ Time Frame: Baseline, 1 week, 8 weeks ]

Show Outcome Measure 8

9. Secondary:

Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale [ Time Frame: Baseline, 1 week, 8 weeks ]

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10. Secondary:

Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale [ Time Frame: Baseline, 1 week, 8 weeks ]

Show Outcome Measure 10

11. Secondary:

Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) [ Time Frame: Baseline, 1 week, 8 weeks ]

Show Outcome Measure 11

12. Secondary:

Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks [ Time Frame: 1 week, 8 weeks ]

Show Outcome Measure 12

13. Secondary:

Time to Onset of Nausea [ Time Frame: Baseline to onset of nausea (Baseline up to 8 weeks) ]

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Measure Type	Secondary
Measure Title	Time to Onset of Nausea
Measure Description	Events of nausea were taken from the adverse event (AE) data. Participants were censored based on the following rules: 1=study discontinuation date if the participant discontinues the study; 2=study lost to follow-up date if the participant drops out of the study.
Time Frame	Baseline to onset of nausea (Baseline up to 8 weeks)
Safety Issue	Yes

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 safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.

Reporting Groups

	Description
Duloxetine 60 mg With Food	Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
Duloxetine 60 mg Without Food	Duloxetine 60 mg capsule po QD without food for 8 weeks
Duloxetine 30 mg With Food	Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
Duloxetine 30 mg Without Food	Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks

Measured Values

	Duloxetine 60 mg With Food	Duloxetine 60 mg Without Food	Duloxetine 30 mg With Food	Duloxetine 30 mg Without Food
Number of Participants Analyzed [units: participants]	40	38	38	37
Time to Onset of Nausea [units: days] Median ( 95% Confidence Interval )	2.0 ( 1.0 to 9.0 )	1.0 ( 1.0 to NA ) ^[1]	7.0 ( 2.0 to 56.0 )	6.0 ( 1.0 to NA ) ^[1]

[1]	The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

No statistical analysis provided for Time to Onset of Nausea

14. Secondary:

Time to Resolve Nausea [ Time Frame: Nausea onset up to nausea resolve (Baseline up to 8 weeks) ]

Show Outcome Measure 14

15. Secondary:

Percentage of Participants Achieving Response [ Time Frame: Baseline up to 8 weeks ]

Show Outcome Measure 15

16. Secondary:

Percentage of Patients Achieving Remission [ Time Frame: Baseline up to 8 weeks ]

Show Outcome Measure 16

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.

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
Large number of protocol violations; bias due to unblinded, open-label design (participants were predisposed to expect an outcome of nausea as the primary endpoint); use of emetogenic medications; incorrect reporting and intake of food and drug.

Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979

No publications provided

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00960986 History of Changes
Other Study ID Numbers:	9884, F1J-MC-HMFL
Study First Received:	August 17, 2009
Results First Received:	January 17, 2012
Last Updated:	March 23, 2012
Health Authority:	Korea: Food and Drug Administration

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