Duloxetine delayed-release capsules are 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 duloxetine delayed-release capsules 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 duloxetine delayed-release capsules in the treatment of chronic low back pain. Patients in all studies had no signs of radiculopathy or spinal stenosis.

: Two hundred thirty-six adult patients (N = 115 on duloxetine delayed-release capsules, N = 121 on placebo) enrolled and 182 (77%) completed 13 week treatment phase. After 7 weeks of treatment, duloxetine delayed-release capsule patients with less than 30% reduction in average daily pain and who were able to tolerate duloxetine 60 mg once daily had their dose of duloxetine delayed-release capsules, 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 duloxetine delayed-release capsules 60 to 120 mg daily had a significantly greater pain reduction compared to placebo. Randomization was Study CLBP-1

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.

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

: Four hundred and one patients were randomized to receive fixed doses of duloxetine delayed-release capsules 60 mg daily or placebo (N = 198 on duloxetine delayed-release capsules, 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 duloxetine delayed-release capsules 60 mg daily had significantly greater pain reduction compared to placebo. Study CLBP-3

For various degrees of improvement in pain from baseline to study endpoint, and 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. Figures 56

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

Severity – CLBP-1

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

Severity – CLBP-3

— Studies in Chronic Pain Due to Osteoarthritis

The efficacy of duloxetine delayed-release capsules 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 duloxetine delayed-release capsules started treatment in both studies at a dose of 30 mg once daily for one week. After the first week, the dose of duloxetine delayed-release capsules was increased to 60 mg once daily. After 7 weeks of treatment with duloxetine delayed-release capsules 60 mg once daily, in OA-1 patients with sub-optimal response to treatment (< 30% pain reduction) and tolerated duloxetine 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 duloxetine delayed-release capsules 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 duloxetine delayed-release capsules 60 mg and 120 mg once daily treatment groups compared to the placebo group.

: Two hundred fifty-six patients (N = 128 on duloxetine delayed-release capsules, 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 duloxetine delayed-release capsules 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-1

: Two hundred thirty-one patients (N = 111 on duloxetine delayed-release capsules, 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 duloxetine delayed-release capsules did not show a significantly greater pain reduction. Study OA-2

In Study OA-1, for various degrees of improvement in pain from baseline to study endpoint, 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 7

Figure 7: Percentage of Patients Achieving Various Levels of Pain Relief as Measured by 24 Hour Average Pain

Severity – OA-1