Effect of Duloxetine 60 mg Once Daily versus Placebo in Patients with Chronic Low Back Pain

Chronic low back pain (CLBP) is generally defined as any pain in the low back
that persists for at least 12 weeks. CLBP is one of the most common
musculoskeletal disorders in developed countries. Back pain in general affects
70% to 85% of all people at some time in their lives, but 90% of affected
individuals recover, typically within 12 weeks. Recovery after 12 weeks is slow
and uncertain, and this subset of patients is extremely difficult to treat, to
the extent that CLBP and related disability are one of the most common
contributors to disability and lost productivity in most industrialized
countries (Williams et al.1998; Andersson 1999; Deyo and Weinstein 2001).
Treatment varies widely, and can include systemic or local pharmacological
treatments, physical therapy, electrotherapy or surgical care. Preliminary
indication that duloxetine is likely to be effective in CLBP comes from some of
the studies in MDD (Major Depressive Disorder), where back pain was evaluated.
Two recently completed 13-week efficacy studies were conducted in patients with
CLBP. In the first study the primary endpoint was not achieved, though the
pattern of response observed on the primary, as well as a number of secondary
efficacy variables, provided a strong suggestion that duloxetine at dosages of
60 mg QD and 120 mg QD might be beneficial in the management of CLBP. The
second study provided substantial evidence that daily treatment with duloxetine
at doses of 60 mg and 120 mg was safe and effective in the treatment of CLBP.
This was demonstrated by significant pain reduction on the primary and most
secondary efficacy assessments, as well as safe administration and good
tolerability during the study. The current study is being conducted to provide
a definitive answer for the use of duloxetine in treating chronic low back
pain.

The primary objective of this study is to assess the efficacy of duloxetine 60
mg once daily (QD) compared with placebo on the reduction of pain severity as
measured by the Brief Pain Inventory (BPI) 24-hour average pain score in
patients with chronic low back pain (CLBP) during a 12-week, double-blind
treatment period. The secondary gatekeeper objectives are:
• to evaluate duloxetine 60 mg QD versus placebo on patients* perceived
improvement as measured by Patient*s Global Impressions of Improvement (PGI-
Improvement) (Guy 1976)
• to evaluate duloxetine 60 mg QD versus placebo on the improvement of
functioning as measured by the Roland Morris Disability Questionnaire (RMDQ-24)
(Roland and Morris 1983).

Method:
Study F1J-MC-HMGC is a multicenter, randomised, phase III, double-blind,
parallel, placebo-controlled comparison trial with 3 study periods.
Approximately 400 patients will be randomized (ratio1:1) at Visit 2 to the 2
treatment groups (200 patients per arm).
Study Period I (Screening) is a 1-week screening phase.
Study Period II (Visit 2-Visit 6) is a double-blind treatment phase of
approximately 12 weeks, during which patients will be randomly assigned at a
1:1 ratio to either duloxetine 60 mg QD or placebo.
Study Period III is a 1-week taper phase (Visit 301). Patients on placebo who
have completed study period II, or who are discontinuing the study after 1 week
of treatment will remain on placebo and will enter the 1 week taper phase.

Duloxetine 60 mg QD or Placebo

Previous studies have shown duloxetine to be a safe drug. Participants will not
be subjected to any interventions other than physical examination, ECG, urine
sample and blood drawing (for chemical/haematological laboratory
investigations). Participants will further be asked to keep an electronic diary
and fill out a number of questionnaires during their visits. Therefore, the
estimated risks of participation are low. Possible unpleasant experiences
include nausea, headaches, dry mouth,somnolence.
The study is divided into 3 periods lasting a total of 14 weeks (after
screening). A total of 7 visits will be scheduled, with intervals varying from
1 and 3 weeks.