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CLINICAL PHARMACOLOGY

Mechanism Of Action

Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS.

Pharmacodynamics

Preclinical studies have shown that duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors in vitro. Duloxetine does not inhibit monoamine oxidase (MAO).

CYMBALTA is in a class of drugs known to affect urethral resistance. If symptoms of urinary hesitation develop during treatment with CYMBALTA, consideration should be given to the possibility that they might be drug-related.

Pharmacokinetics

Duloxetine has an elimination half-life of about 12 hours (range 8 to 17 hours) and its pharmacokinetics are dose proportional over the therapeutic range. Steady-state plasma concentrations are typically achieved after 3 days of dosing. Elimination of duloxetine is mainly through hepatic metabolism involving two P450 isozymes, CYP1A2 and CYP2D6.

Absorption and Distribution

Orally administered duloxetine hydrochloride is well absorbed. There is a median 2 hour lag until absorption begins (Tlag), with maximal plasma concentrations (Cmax) of duloxetine occurring 6 hours post dose. Food does not affect the Cmax of duloxetine, but delays the time to reach peak concentration from 6 to 10 hours and it marginally decreases the extent of absorption (AUC) by about 10%. There is a 3 hour delay in absorption and a one-third increase in apparent clearance of duloxetine after an evening dose as compared to a morning dose.

The apparent volume of distribution averages about 1640 L. Duloxetine is highly bound ( > 90%) to proteins in human plasma, binding primarily to albumin and α1-acid glycoprotein. The interaction between duloxetine and other highly protein bound drugs has not been fully evaluated. Plasma protein binding of duloxetine is not affected by renal or hepatic impairment.

Metabolism and Elimination

Biotransformation and disposition of duloxetine in humans have been determined following oral administration of 14C-labeled duloxetine. Duloxetine comprises about 3% of the total radiolabeled material in the plasma, indicating that it undergoes extensive metabolism to numerous metabolites. The major biotransformation pathways for duloxetine involve oxidation of the naphthyl ring followed by conjugation and further oxidation. Both CYP1A2 and CYP2D6 catalyze the oxidation of the naphthyl ring in vitro. Metabolites found in plasma include 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate. Many additional metabolites have been identified in urine, some representing only minor pathways of elimination. Only trace ( < 1% of the dose) amounts of unchanged duloxetine are present in the urine. Most (about 70%) of the duloxetine dose appears in the urine as metabolites of duloxetine; about 20% is excreted in the feces. Duloxetine undergoes extensive metabolism, but the major circulating metabolites have not been shown to contribute significantly to the pharmacologic activity of duloxetine.

Children and Adolescents (ages 7 to 17 years)

Duloxetine steady-state plasma concentration was comparable in children (7 to 12 years of age), adolescents (13 to 17 years of age) and adults. The average steady-state duloxetine concentration was approximately 30% lower in the pediatric population (children and adolescents) relative to the adults. The model-predicted duloxetine steady state plasma concentrations in children and adolescents were mostly within the concentration range observed in adult patients and did not exceed the concentration range in adults.

Clinical Studies

The efficacy of CYMBALTA has been established in the following adequate and well-controlled trials:

  • Major Depressive Disorder (MDD): 4 short-term and 1 maintenance trial in adults [see Major Depressive Disorder].
  • Generalized Anxiety Disorder (GAD): 3 short-term trials in adults, 1 maintenance trial in adults, and 1 short-term trial in children and adolescents [see Generalized Anxiety Disorder].
  • Diabetic Peripheral Neuropathic Pain (DPNP): Two 12-week trials in adults [see Diabetic Peripheral Neuropathic Pain].
  • Fibromyalgia (FM): Two trials in adults (one of 3 months duration and one of 6 months duration) [see Fibromyalgia].
  • Chronic Musculoskeletal Pain: Two 12- to 13-week trials in adult patients with chronic low back pain (CLBP) and one 13-week trial in adult patients with chronic pain due to osteoarthritis [see Chronic Musculoskeletal Pain].

Major Depressive Disorder

The efficacy of CYMBALTA as a treatment for depression was established in 4 randomized, double-blind, placebo-controlled, fixed-dose studies in adult outpatients (18 to 83 years) meeting DSM-IV criteria for major depression. In 2 studies, patients were randomized to CYMBALTA 60 mg once daily (N=123 and N=128, respectively) or placebo (N=122 and N=139, respectively) for 9 weeks; in the third study, patients were randomized to CYMBALTA 20 or 40 mg twice daily (N=86 and N=91, respectively) or placebo (N=89) for 8 weeks; in the fourth study, patients were randomized to CYMBALTA 40 or 60 mg twice daily (N=95 and N=93, respectively) or placebo (N=93) for 8 weeks. There is no evidence that doses greater than 60 mg/day confer additional benefits.

In all 4 studies, CYMBALTA demonstrated superiority over placebo as measured by improvement in the 17-item Hamilton Depression Rating Scale (HAMD-17) total score (Studies 1-4 in Table 7).

In all of these clinical studies, analyses of the relationship between treatment outcome and age, gender, and race did not suggest any differential responsiveness on the basis of these patient characteristics.

Table 7: Summary of the Primary Efficacy Results for Studies in Major Depressive Disorder

Study Number Treatment Group Primary Efficacy Measure: HAMD-17
Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Difference9 (95% CI)
Study 1 CYMBALTA (60 mg/day)b 21.5 (4.10) -10.9 (0.70) -4.9 (-6.8, -2.9)
Placebo 21.1 (3.71) -6.1 (0.69) --
Study 2 CYMBALTA (60 mg/day)b 20.3 (3.32) -10.5 (0.71) -2.2 (-4.0, -0.3)
Placebo 20.5 (3.42) -8.3 (0.67) --
Study 3 CYMBALTA (20 mg BID)d 18.6 (5.85) -7.4 (0.80) -2.4 (-4.7, -0.2)
CYMBALTA (40 mg BID)d 18.1    (4.52) -8.6 (0.81) -3.6 (-5.9, -1.4)
Placebo 17.2    (5.11) -5.0 (0.81) --
Study 4 CYMBALTA (40 mg BID)b 19.9    (3.54) -11.0 (0.49) -2.2 (-3.6, -0.9)
CYMBALTA (60 mg BID)b 20.2 (3.41) -12.1 (0.49) -3.3 (-4.7, -1.9)
Placebo 19.9    (3.58) -8.8 (0.50) --
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval, not adjusted for multiplicity in trials where multiple dose groups were included.
aDifference (drug minus placebo) in least-squares mean change from baseline.
bDoses statistically significantly superior to placebo.

In another study, 533 patients meeting DSM-IV criteria for MDD received CYMBALTA 60 mg once daily during an initial 12-week open-label treatment phase. Two hundred and seventy-eight patients who responded to open label treatment (defined as meeting the following criteria at weeks 10 and 12: a HAMD-17 total score ≤ 9, Clinical Global Impressions of Severity (CGI-S) ≤ 2, and not meeting the DSM-IV criteria for MDD) were randomly assigned to continuation of CYMBALTA at the same dose (N=136) or to placebo (N=142) for 6 months. Patients on CYMBALTA experienced a statistically significantly longer time to relapse of depression than did patients on placebo (Study 5 in Figure 1). Relapse was defined as an increase in the CGI-S score of ≥ 2 points compared with that obtained at week 12, as well as meeting the DSM-IV criteria for MDD at 2 consecutive visits at least 2 weeks apart, where the 2-week temporal criterion had to be satisfied at only the second visit. The effectiveness of CYMBALTA in hospitalized patients with major depressive disorder has not been studied.

Figure 1: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse (MDD Study 5)

Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse - Illustration

Generalized Anxiety Disorder

The efficacy of CYMBALTA in the treatment of generalized anxiety disorder (GAD) was established in 1 fixed-dose randomized, double-blind, placebo-controlled trial and 2 flexible-dose randomized, double-blind, placebo-controlled trials in adult outpatients between 18 and 83 years of age meeting the DSM-IV criteria for GAD.

In 1 flexible-dose study and in the fixed-dose study, the starting dose was 60 mg once daily where down titration to 30 mg once daily was allowed for tolerability reasons before increasing it to 60 mg once daily. Fifteen percent of patients were down titrated. One flexible-dose study had a starting dose of 30 mg once daily for 1 week before increasing it to 60 mg once daily.

The 2 flexible-dose studies involved dose titration with CYMBALTA doses ranging from 60 mg once daily to 120 mg once daily (N=168 and N=162) compared to placebo (N=159 and N=161) over a 10-week treatment period. The mean dose for completers at endpoint in the flexible-dose studies was 104.75 mg/day. The fixed-dose study evaluated CYMBALTA doses of 60 mg once daily (N=168) and 120 mg once daily (N=170) compared to placebo (N=175) over a 9week treatment period. While a 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit.

In all 3 studies, CYMBALTA demonstrated superiority over placebo as measured by greater improvement in the Hamilton Anxiety Scale (HAM-A) total score (Studies 1-3 in Table 8) and by the Sheehan Disability Scale (SDS) global functional impairment score. The SDS is a composite measurement of the extent emotional symptoms disrupt patient functioning in 3 life domains: work/school, social life/leisure activities, and family life/home responsibilities.

In another study, 887 patients meeting DSM-IV-TR criteria for GAD received CYMBALTA 60 mg to 120 mg once daily during an initial 26-week open-label treatment phase. Four hundred and twenty-nine patients who responded to open-label treatment (defined as meeting the following criteria at weeks 24 and 26: a decrease from baseline HAM-A total score by at least 50% to a score no higher than 11, and a Clinical Global Impressions of Improvement [CGI-Improvement] score of 1 or 2) were randomly assigned to continuation of CYMBALTA at the same dose (N=216) or to placebo (N=213) and were observed for relapse. Of the patients randomized, 73% had been in a responder status for at least 10 weeks. Relapse was defined as an increase in CGI-Severity score at least 2 points to a score ≥ 4 and a MINI (Mini-International Neuropsychiatric Interview) diagnosis of GAD (excluding duration), or discontinuation due to lack of efficacy. Patients taking CYMBALTA experienced a statistically significantly longer time to relapse of GAD than did patients taking placebo (Study 4 in Figure 2).

Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender.

The efficacy of CYMBALTA in the treatment of patients ≥ 65 years of age with generalized anxiety disorder was established in one 10-week flexible-dose, randomized, double-blind, placebo-controlled trial in adults ≥ 65 years of age meeting the DSM-IV criteria for GAD. In this study, the starting dose was 30 mg once daily for 2 weeks before further dose increases in 30 mg increments at treatment weeks 2, 4, and 7 up to 120 mg once daily were allowed based on investigator judgment of clinical response and tolerability. The mean dose for patients completing the 10-week acute treatment phase was 50.95 mg. Patients treated with CYMBALTA (N=151) demonstrated significantly greater improvement compared with placebo (N=140) on mean change from baseline to endpoint as measured by the Hamilton Anxiety Rating Scale total score (Study 5 in Table 8).

The efficacy of CYMBALTA in the treatment of pediatric patients 7 to 17 years of age with generalized anxiety disorder (GAD) was established in 1 flexible-dose randomized, double-blind, placebo-controlled trial in pediatric outpatients with GAD (based on DSM-IV criteria).

In this study, the starting dose was 30 mg once daily for 2 weeks. Further dose increases in 30 mg increments up to 120 mg once daily were allowed based on investigator judgment of clinical response and tolerability. The mean dose for patients completing the 10-week treatment phase was 57.6 mg/day. In this study, CYMBALTA (N=135) demonstrated superiority over placebo (N=137) from baseline to endpoint as measured by greater improvement in the Pediatric Anxiety Rating Scale (PARS) for GAD severity score (Study 6 in Table 8).

Table 8: Summary of the Primary Efficacy Results for Studies in General Anxiety Disorder

Study Number Treatment Group Primary Efficacy Measure
Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Differencea(95% CI)
Study 1 (HAM-A) CYMBALTA (60 mg/day)b 25.1 (7.18) -12.8 (0.68) -4.4 (-6.2, -2.5)
CYMBALTA (120 mg/day)b 25.1 (7.24) -12.5 (0.67) -4.1 (-5.9, -2.3)
Placebo 25.8 (7.66) -8.4 (0.67) --
Study 2 (HAM-A) CYMBALTA (60-120 mg/day)b 22.5 (7.44) -8.1 (0.70) -2.2 (-4.2, -0.3)
Placebo 23.5 (7.91) -5.9 (0.70) --
Study 3 (HAM-A) CYMBALTA (60-120 mg/day)b 25.8 (5.66) -11.8 (0.69) -2.6 (-4.5, -0.7)
Placebo 25.0 (5.82) -9.2 (0.67) --
Study 5 (elderly) (HAM-A) CYMBALTA (60-120 mg/day)b 24.6 (6.21) -15.9 (0.63) -4.2 (-5.9, -2.5)
Placebo 24.5 (7.05) -11.7 (0.67) --
Study 6 (Pediatric) (PARS for GAD) CYMBALTA (30-120 mg/day)b 17.5 (1.98) -9.7 (0.50) -2.7 (-4.0, -1.3)
Placebo 17.4 (2.24) -7.1 (0.50) --
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval, not adjusted for multiplicity in trials where multiple dose groups were included.
aDifference (drug minus placebo) in least squares mean change from baseline.
bDose statistically significantly superior to placebo.

Figure 2: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse (GAD Study 4)

Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse - Illustration

Diabetic Peripheral Neuropathic Pain

The efficacy of CYMBALTA for the management of neuropathic pain associated with diabetic peripheral neuropathy was established in 2 randomized, 12-week, double-blind, placebo-controlled, fixed-dose studies in adult patients having diabetic peripheral neuropathic pain for at least 6 months. Study DPNP-1 and Study DPNP-2 enrolled a total of 791 patients of whom 592 (75%) completed the studies. Patients enrolled had Type I or II diabetes mellitus with a diagnosis of painful distal symmetrical sensorimotor polyneuropathy for at least 6 months. The patients had a baseline pain score of ≥ 4 on an 11-point scale ranging from 0 (no pain) to 10 (worst possible pain). Patients were permitted up to 4 g of acetaminophen per day as needed for pain, in addition to CYMBALTA. Patients recorded their pain daily in a diary.

Both studies compared CYMBALTA 60 mg once daily or 60 mg twice daily with placebo. DPNP-1 additionally compared CYMBALTA 20 mg with placebo. A total of 457 patients (342 CYMBALTA, 115 placebo) were enrolled in DPNP-1 and a total of 334 patients (226 CYMBALTA, 108 placebo) were enrolled in DPNP-2. Treatment with CYMBALTA 60 mg one or two times a day statistically significantly improved the endpoint mean pain scores from baseline and increased the proportion of patients with at least a 50% reduction in pain scores from baseline. For various degrees of improvement in pain from baseline to study endpoint, Figures 3 and 4 show the fraction of patients achieving that degree of improvement. The figures are cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as week 1, which persisted throughout the study.

Figure 3: Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity - DPNP-1

Percentage of Patients Achieving Various Levels of Pain Relief - Illustration

Figure 4: Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity - DPNP-2

Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity - DPNP-2 - Illustration

Fibromyalgia

The efficacy of CYMBALTA for the management of fibromyalgia was established in two randomized, double-blind, placebo-controlled, fixed-dose studies in adult patients meeting the American College of Rheumatology criteria for fibromyalgia (a history of widespread pain for 3 months, and pain present at 11 or more of the 18 specific tender point sites). Study FM-1 was three months in duration and enrolled female patients only. Study FM-2 was six months in duration and enrolled male and female patients. Approximately 25% of participants had a comorbid diagnosis of major depressive disorder (MDD). FM-1 and FM-2 enrolled a total of 874 patients of whom 541 (62%) completed the studies. The patients had a baseline pain score of 6.5 on an 11-point scale ranging from 0 (no pain) to 10 (worse possible pain).

Both studies compared CYMBALTA 60 mg once daily or 120 mg daily (given in divided doses in FM-1 and as a single daily dose in FM-2) with placebo. FM-2 additionally compared CYMBALTA 20 mg with placebo during the initial three months of a six-month study. A total of 354 patients (234 CYMBALTA, 120 placebo) were enrolled in FM-1 and a total of 520 patients (376 CYMBALTA, 144 placebo) were enrolled in FM-2 (5% male, 95% female). Treatment with CYMBALTA 60 mg or 120 mg daily statistically significantly improved the endpoint mean pain scores from baseline and increase the proportion of patients with at least a 50% reduction in pain score from baseline. Pain reduction was observed in patients both with and without comorbid MDD. However, the degree of pain reduction may be greater in patients with comorbid MDD. For various degrees of improvement in pain from baseline to study endpoint, Figures 5 and 6 show the fraction of patients achieving that degree of improvement. The figures are cumulative so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as week 1, which persisted throughout the study. Improvement was also demonstrated on measures of function (Fibromyalgia Impact Questionnaires) and patient global impression of change (PGI). Neither study demonstrated a benefit of 120 mg compared to 60 mg, and a higher dose was associated with more adverse reactions and premature discontinuations of treatment.

Figure 5: Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity - FM-1

Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity - FM-1 - Illustration

Figure 6: Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity - FM-2

Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity - FM-2 - Illustration

Additionally, the benefit of up-titration in non-responders to CYMBALTA at 60 mg/day was evaluated in a separate study. Patients were initially treated with CYMBALTA 60 mg once daily for eight weeks in open-label fashion. Subsequently, completers of this phase were randomized to double-blind treatment with CYMBALTA at either 60 mg once daily or 120 mg once daily. Those patients who were considered non-responders, where response was defined as at least a 30% reduction in pain score from baseline at the end of the 8-week treatment, were no more likely to meet response criteria at the end of 60 weeks of treatment if blindly titrated to CYMBALTA 120 mg as compared to those who were blindly continued on CYMBALTA 60 mg.

Chronic Musculoskeletal Pain

CYMBALTA is indicated for the management of chronic musculoskeletal pain. This has been established in studies in patients with chronic low back pain and chronic pain due to osteoarthritis.

Studies in Chronic Low Back Pain

The efficacy of CYMBALTA in chronic low back pain (CLBP) was assessed in two double-blind, placebo-controlled, randomized clinical trials of 13-weeks duration (Study CLBP-1 and Study CLBP-2), and one of 12-weeks duration (CLBP-3). CLBP-1 and CLBP-3 demonstrated efficacy of CYMBALTA in the treatment of chronic low back pain. Patients in all studies had no signs of radiculopathy or spinal stenosis.

Study CLBP-1: Two hundred thirty-six adult patients (N=115 on CYMBALTA, N=121 on placebo) enrolled and 182 (77%) completed 13-week treatment phase. After 7 weeks of treatment, CYMBALTA patients with less than 30% reduction in average daily pain and who were able to tolerate CYMBALTA 60 mg once daily had their dose of CYMBALTA, in a double-blinded fashion, increased to 120 mg once daily for the remainder of the study. Patients had a mean baseline pain rating of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain). After 13 weeks of treatment, patients taking CYMBALTA 60-120 mg daily had a significantly greater pain reduction compared to placebo. Randomization was stratified by the patients' baseline NSAIDs-use status. Subgroup analyses did not indicate that there were differences in treatment outcomes as a function of NSAIDs use.

Study CLBP-2: Four hundred and four patients were randomized to receive fixed doses of CYMBALTA daily or a matching placebo (N=59 on CYMBALTA 20 mg, N=116 on CYMBALTA 60 mg, N=112 on CYMBALTA 120 mg, N=117 on placebo) and 267 (66%) completed the entire 13-week study. After 13 weeks of treatment, none of the three CYMBALTA doses showed a statistically significant difference in pain reduction compared to placebo.

Study CLBP-3: Four hundred and one patients were randomized to receive fixed doses of CYMBALTA 60 mg daily or placebo (N=198 on CYMBALTA, N=203 on placebo), and 303 (76%) completed the study. Patients had a mean baseline pain rating of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain). After 12 weeks of treatment, patients taking CYMBALTA 60 mg daily had significantly greater pain reduction compared to placebo.

For various degrees of improvement in pain from baseline to study endpoint, Figures 7 and 8 show the fraction of patients in CLBP-1 and CLBP-3 achieving that degree of improvement. The figures are cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned the value of 0% improvement.

Figure 7: Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity – CLBP-1

Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity – CLBP-1 - Illustration

Figure 8: Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity – CLBP-3

Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity – CLBP-3 - Illustration

Studies in Chronic Pain Due to Osteoarthritis

The efficacy of CYMBALTA in chronic pain due to osteoarthritis was assessed in 2 double-blind, placebo-controlled, randomized clinical trials of 13-weeks duration (Study OA-1 and Study OA-2). All patients in both studies fulfilled the ACR clinical and radiographic criteria for classification of idiopathic osteoarthritis of the knee. Randomization was stratified by the patients' baseline NSAIDs-use status. Patients assigned to CYMBALTA started treatment in both studies at a dose of 30 mg once daily for one week. After the first week, the dose of CYMBALTA was increased to 60 mg once daily. After 7 weeks of treatment with CYMBALTA 60 mg once daily, in OA-1 patients with sub-optimal response to treatment ( < 30% pain reduction) and tolerated CYMBALTA 60 mg once daily had their dose increased to 120 mg. However, in OA-2, all patients, regardless of their response to treatment after 7 weeks, were re-randomized to either continue receiving CYMBALTA 60 mg once daily or have their dose increased to 120 mg once daily for the remainder of the study. Patients in the placebo treatment groups in both studies received a matching placebo for the entire duration of studies. For both studies, efficacy analyses were conducted using 13-week data from the combined CYMBALTA 60 mg and 120 mg once daily treatment groups compared to the placebo group.

Study OA-1: Two hundred fifty-six patients (N=128 on CYMBALTA, N=128 on placebo) enrolled and 204 (80%) completed the study. Patients had a mean baseline pain rating of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain). After 13 weeks of treatment, patients taking CYMBALTA had significantly greater pain reduction. Subgroup analyses did not indicate that there were differences in treatment outcomes as a function of NSAIDs use.

Study OA-2: Two hundred thirty-one patients (N=111 on CYMBALTA, N=120 on placebo) enrolled and 173 (75%) completed the study. Patients had a mean baseline pain of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain). After 13 weeks of treatment, patients taking CYMBALTA did not show a significantly greater pain reduction.

In Study OA-1, for various degrees of improvement in pain from baseline to study endpoint, Figure 7 shows the fraction of patients achieving that degree of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned the value of 0% improvement.

Figure 9: Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity – OA-1

Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity – OA-1 - Illustration

Last reviewed on RxList: 10/31/2014
This monograph has been modified to include the generic and brand name in many instances.

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