Trial Outcomes & Findings for A Study of Duloxetine in Patients With Osteoarthritis Knee Pain (NCT NCT00945945)

Last Updated: 2011-03-08

Results Overview

A self-reported measure of the severity of pain based on the average pain over 24-hours. Severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). BOCF endpoint was defined as the baseline value for participants discontinued during acute phase, and defined as the last non-missing observation in the treatment phase for all other randomized participants. Due to the nature of a study drug labeling error which led to a treatment crossover (see Arms), data from protocol-defined treatment groups were compromised. The results from each mixed-treatment group are presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

424 participants

Primary outcome timeframe

Baseline, 13 weeks

Results posted on

2011-03-08

Participant Flow

Due to a study drug labeling error which led to a treatment crossover, the intended comparisons for group-level differences between duloxetine and placebo cannot be made. The results from comparisons of mixed-treatment groups are presented for primary efficacy and safety outcomes.

Participant milestones

Participant milestones
Measure	DLX30-PLA Per the protocol, patients randomized to the duloxetine group were to receive duloxetine for the entire 13-week acute treatment period. Patients were to start at a 30 mg daily (QD) dose of duloxetine for 1 week, then increase to 60 mg QD of duloxetine for the following 12 weeks. However, due to a study drug labeling error, patients randomized to this group received 30 mg of duloxetine for the initial 1-week, but received placebo instead of receiving 60 mg QD of duloxetine for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as DLX30-PLA throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive 30 mg QD of duloxetine during that week, and that did occur per protocol.	PLA-DLX60 Per the protocol, patients randomized to the placebo group were to receive placebo for the entire 13-week acute treatment period. Patients were to start on placebo for the first week, then continue on placebo for the following 12 weeks. However, due to a study drug labeling error, patients in this group received placebo for the initial 1-week, but received 60 mg QD of duloxetine instead of receiving placebo for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as PLA-DLX60 throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive placebo that week, and that did occur per protocol.
Overall Study STARTED	207	217
Overall Study COMPLETED	171	162
Overall Study NOT COMPLETED	36	55

Reasons for withdrawal

Reasons for withdrawal
Measure	DLX30-PLA Per the protocol, patients randomized to the duloxetine group were to receive duloxetine for the entire 13-week acute treatment period. Patients were to start at a 30 mg daily (QD) dose of duloxetine for 1 week, then increase to 60 mg QD of duloxetine for the following 12 weeks. However, due to a study drug labeling error, patients randomized to this group received 30 mg of duloxetine for the initial 1-week, but received placebo instead of receiving 60 mg QD of duloxetine for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as DLX30-PLA throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive 30 mg QD of duloxetine during that week, and that did occur per protocol.	PLA-DLX60 Per the protocol, patients randomized to the placebo group were to receive placebo for the entire 13-week acute treatment period. Patients were to start on placebo for the first week, then continue on placebo for the following 12 weeks. However, due to a study drug labeling error, patients in this group received placebo for the initial 1-week, but received 60 mg QD of duloxetine instead of receiving placebo for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as PLA-DLX60 throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive placebo that week, and that did occur per protocol.
Overall Study Adverse Event	15	35
Overall Study Withdrawal by Subject	7	10
Overall Study Lost to Follow-up	4	5
Overall Study Lack of Efficacy	6	2
Overall Study Protocol Violation	4	2
Overall Study Entry Criteria Not Met	0	1

Baseline Characteristics

A Study of Duloxetine in Patients With Osteoarthritis Knee Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DLX30-PLA n=207 Participants Per the protocol, patients randomized to the duloxetine group were to receive duloxetine for the entire 13-week acute treatment period. Patients were to start at a 30 mg daily (QD) dose of duloxetine for 1 week, then increase to 60 mg QD of duloxetine for the following 12 weeks. However, due to a study drug labeling error, patients randomized to this group received 30 mg of duloxetine for the initial 1-week, but received placebo instead of receiving 60 mg QD of duloxetine for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as DLX30-PLA throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive 30 mg QD of duloxetine during that week, and that did occur per protocol.	PLA-DLX60 n=217 Participants Per the protocol, patients randomized to the placebo group were to receive placebo for the entire 13-week acute treatment period. Patients were to start on placebo for the first week, then continue on placebo for the following 12 weeks. However, due to a study drug labeling error, patients in this group received placebo for the initial 1-week, but received 60 mg QD of duloxetine instead of receiving placebo for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as PLA-DLX60 throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive placebo that week, and that did occur per protocol.	Total n=424 Participants Total of all reporting groups
Age Continuous	63.40 years STANDARD_DEVIATION 9.90 • n=5 Participants	64.18 years STANDARD_DEVIATION 10.06 • n=7 Participants	63.80 years STANDARD_DEVIATION 9.97 • n=5 Participants
Sex: Female, Male Female	147 Participants n=5 Participants	141 Participants n=7 Participants	288 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	76 Participants n=7 Participants	136 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=5 Participants	27 Participants n=7 Participants	53 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	181 Participants n=5 Participants	190 Participants n=7 Participants	371 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) White	196 Participants n=5 Participants	203 Participants n=7 Participants	399 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	81 participants n=5 Participants	92 participants n=7 Participants	173 participants n=5 Participants
Region of Enrollment Puerto Rico	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Greece	13 participants n=5 Participants	11 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment Spain	25 participants n=5 Participants	23 participants n=7 Participants	48 participants n=5 Participants
Region of Enrollment Romania	16 participants n=5 Participants	19 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment Russian Federation	33 participants n=5 Participants	32 participants n=7 Participants	65 participants n=5 Participants
Region of Enrollment Germany	18 participants n=5 Participants	19 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Sweden	18 participants n=5 Participants	17 participants n=7 Participants	35 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 13 weeks

Population: Number of randomized participants with a non-missing baseline and BOCF endpoint.

Outcome measures

Outcome measures
Measure	DLX30-PLA n=207 Participants Per the protocol, patients randomized to the duloxetine group were to receive duloxetine for the entire 13-week acute treatment period. Patients were to start at a 30 mg daily (QD) dose of duloxetine for 1 week, then increase to 60 mg QD of duloxetine for the following 12 weeks. However, due to a study drug labeling error, patients randomized to this group received 30 mg of duloxetine for the initial 1-week, but received placebo instead of receiving 60 mg QD of duloxetine for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as DLX30-PLA throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive 30 mg QD of duloxetine during that week, and that did occur per protocol.	PLA-DLX60 n=217 Participants Per the protocol, patients randomized to the placebo group were to receive placebo for the entire 13-week acute treatment period. Patients were to start on placebo for the first week, then continue on placebo for the following 12 weeks. However, due to a study drug labeling error, patients in this group received placebo for the initial 1-week, but received 60 mg QD of duloxetine instead of receiving placebo for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as PLA-DLX60 throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive placebo that week, and that did occur per protocol.
Change From Baseline to 13 Week Endpoint (Baseline Observation Carried Forward [BOCF]) in Brief Pain Inventory (BPI) "24-Hour Average Pain" Item (Question 3) of the BPI-Modified Short Form Score Change from Baseline to Endpoint (BOCF)	-1.93 units on a scale Standard Deviation 2.23	-2.34 units on a scale Standard Deviation 2.30
Change From Baseline to 13 Week Endpoint (Baseline Observation Carried Forward [BOCF]) in Brief Pain Inventory (BPI) "24-Hour Average Pain" Item (Question 3) of the BPI-Modified Short Form Score Baseline	6.00 units on a scale Standard Deviation 1.28	6.10 units on a scale Standard Deviation 1.31

SECONDARY outcome

Timeframe: Baseline through 13 weeks

Population: All randomized participants.

C-SSRS: scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of patients with suicidal behaviors and ideations are provided. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation.

Outcome measures

Outcome measures
Measure	DLX30-PLA n=207 Participants Per the protocol, patients randomized to the duloxetine group were to receive duloxetine for the entire 13-week acute treatment period. Patients were to start at a 30 mg daily (QD) dose of duloxetine for 1 week, then increase to 60 mg QD of duloxetine for the following 12 weeks. However, due to a study drug labeling error, patients randomized to this group received 30 mg of duloxetine for the initial 1-week, but received placebo instead of receiving 60 mg QD of duloxetine for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as DLX30-PLA throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive 30 mg QD of duloxetine during that week, and that did occur per protocol.	PLA-DLX60 n=217 Participants Per the protocol, patients randomized to the placebo group were to receive placebo for the entire 13-week acute treatment period. Patients were to start on placebo for the first week, then continue on placebo for the following 12 weeks. However, due to a study drug labeling error, patients in this group received placebo for the initial 1-week, but received 60 mg QD of duloxetine instead of receiving placebo for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as PLA-DLX60 throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive placebo that week, and that did occur per protocol.
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Ideation: Wish to be dead	1 participants	0 participants
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Ideation: Active suicidal ideation without intent	0 participants	0 participants
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Ideation: Active suicidal ideation with intent	0 participants	0 participants
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Ideation:Active suicidal ideation with plan to act	0 participants	0 participants
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Behavior: Preparatory acts or behavior	0 participants	0 participants
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Behavior: Aborted attempt	0 participants	0 participants
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Behavior: Interrupted attempt	0 participants	0 participants
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Acts: Non-fatal suicide attempt	0 participants	0 participants
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Acts: Completed suicide	0 participants	0 participants
Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale Ideation: Non-specific active suicidal thoughts	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, 13 weeks

A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). Due to the nature of a study drug labeling error and the resultant treatment crossover (see Arms), the data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline, 13 weeks

The WOMAC index (pain, stiffness, physical function subscales) was completed by the patient. The index has 24 questions. Each question is answered using a 5-point Likert scale (0 to 4). The Total score has a range from 0 (none) to 96 (extreme). Due to the nature of a study drug labeling error and the resultant treatment crossover (see Arms), data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 13 weeks

Self-reported scale measuring pain severity. Severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Four questions assess worst pain, least pain, and average pain in the past 24 hours, and pain right now. Total score ranges from 0-40. Due to the nature of a study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 13 weeks

Interference scores range from 0 (does not interfere) to 10 (completely interferes) on 7 questions assessing interference of pain for general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life. Total score ranges from 0-70. Due to the nature of study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 13 weeks

Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Due to the nature of a study drug labeling error and the resultant treatment crossover (see Arms), the data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 13 weeks

An 11-item questionnaire to individually and jointly assess intermittent and constant pain. Questions assess intensity and impact of pain on activity and emotion. Each item is scored from 0 to 4; higher values indicate higher severity. Total Pain score ranges from 0-44. Due to the nature of study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 13 weeks

BPOMS measures mood states and has 6 factors: tension-anxiety, depression-dejection, anxiety-hostility, fatigue, confusion, and vigor. Item scores: 0 (not at all) to 4 (extremely). Each factor scores range from 0-20. Total score = sum of all factor scores minus vigor score. Due to nature of study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 13 weeks

Patients rate their health state in 5 domains: mobility, self-care, usual activities, pain, and mood. Score between 1-3 is generated for each domain which is mapped to single index score. Index ranges between 0-1; higher scores indicate better health perceived by patient. Due to nature of study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 13 weeks

Self-reported questionnaire with 36 questions covering 8 health domains. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. Due to the nature of a study drug labeling error and the resultant treatment crossover (see Arms), the data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.

Outcome measures

Outcome data not reported

Adverse Events

DLX30-PLA

Serious events: 3 serious events

Other events: 105 other events

Deaths: 0 deaths

PLA-DLX60

Serious events: 2 serious events

Other events: 143 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DLX30-PLA n=207 participants at risk Per the protocol, patients randomized to the duloxetine group were to receive duloxetine for the entire 13-week acute treatment period. Patients were to start at a 30 mg daily (QD) dose of duloxetine for 1 week, then increase to 60 mg QD of duloxetine for the following 12 weeks. However, due to a study drug labeling error, patients randomized to this group received 30 mg of duloxetine for the initial 1-week, but received placebo instead of receiving 60 mg QD of duloxetine for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as DLX30-PLA throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive 30 mg QD of duloxetine during that week, and that did occur per protocol.	PLA-DLX60 n=217 participants at risk Per the protocol, patients randomized to the placebo group were to receive placebo for the entire 13-week acute treatment period. Patients were to start on placebo for the first week, then continue on placebo for the following 12 weeks. However, due to a study drug labeling error, patients in this group received placebo for the initial 1-week, but received 60 mg QD of duloxetine instead of receiving placebo for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as PLA-DLX60 throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive placebo that week, and that did occur per protocol.
Hepatobiliary disorders Cholelithiasis	0.48% 1/207 • Number of events 1	0.00% 0/217
Infections and infestations Neuroborreliosis	0.00% 0/207	0.46% 1/217 • Number of events 1
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/207	0.46% 1/217 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.48% 1/207 • Number of events 1	0.00% 0/217
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.48% 1/207 • Number of events 1	0.00% 0/217

Other adverse events

Other adverse events
Measure	DLX30-PLA n=207 participants at risk Per the protocol, patients randomized to the duloxetine group were to receive duloxetine for the entire 13-week acute treatment period. Patients were to start at a 30 mg daily (QD) dose of duloxetine for 1 week, then increase to 60 mg QD of duloxetine for the following 12 weeks. However, due to a study drug labeling error, patients randomized to this group received 30 mg of duloxetine for the initial 1-week, but received placebo instead of receiving 60 mg QD of duloxetine for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as DLX30-PLA throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive 30 mg QD of duloxetine during that week, and that did occur per protocol.	PLA-DLX60 n=217 participants at risk Per the protocol, patients randomized to the placebo group were to receive placebo for the entire 13-week acute treatment period. Patients were to start on placebo for the first week, then continue on placebo for the following 12 weeks. However, due to a study drug labeling error, patients in this group received placebo for the initial 1-week, but received 60 mg QD of duloxetine instead of receiving placebo for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as PLA-DLX60 throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive placebo that week, and that did occur per protocol.
Gastrointestinal disorders Constipation	3.4% 7/207 • Number of events 7	5.5% 12/217 • Number of events 12
Gastrointestinal disorders Diarrhoea	3.4% 7/207 • Number of events 7	6.5% 14/217 • Number of events 14
Gastrointestinal disorders Dry mouth	5.3% 11/207 • Number of events 11	8.8% 19/217 • Number of events 20
Gastrointestinal disorders Nausea	10.1% 21/207 • Number of events 21	18.9% 41/217 • Number of events 43
General disorders Fatigue	1.4% 3/207 • Number of events 3	7.8% 17/217 • Number of events 17
Infections and infestations Nasopharyngitis	7.7% 16/207 • Number of events 18	0.46% 1/217 • Number of events 1
Metabolism and nutrition disorders Decreased appetite	2.4% 5/207 • Number of events 5	7.4% 16/217 • Number of events 16
Nervous system disorders Dizziness	2.9% 6/207 • Number of events 6	12.0% 26/217 • Number of events 26
Nervous system disorders Headache	9.2% 19/207 • Number of events 21	9.7% 21/217 • Number of events 23
Nervous system disorders Somnolence	1.9% 4/207 • Number of events 4	5.1% 11/217 • Number of events 11
Psychiatric disorders Insomnia	1.9% 4/207 • Number of events 4	6.0% 13/217 • Number of events 15
Skin and subcutaneous tissue disorders Hyperhidrosis	0.97% 2/207 • Number of events 3	6.0% 13/217 • Number of events 13

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60