title: A randomized, double-blind, placebo-controlled trial and open-label extension study to evaluate the efficacy and safety of pregabalin in the treatment of neuropathic pain associated with human immunodeficiency virus neuropathy.
abstract: The objective of these studies was to assess the efficacy and safety of pregabalin in the treatment of human immunodeficiency virus (HIV)-associated neuropathic pain. Patients with HIV-associated distal sensory polyneuropathy (DSP) were randomized to treatment with flexible-dose pregabalin (150-600 mg/day) or placebo for 17 weeks in a single-blind, placebo lead-in, randomized, double-blind, parallel-group, placebo-controlled multinational trial. The primary efficacy outcome was the change in mean pain score on an 11-point numeric rating scale (NRS) from baseline to study endpoint. Participants who completed this trial were invited to participate in a 6-month open-label extension study with pregabalin. Of the 377 patients enrolled in the randomized controlled trial (pregabalin, n=183; placebo, n=194), 68.4% completed treatment. In the open-label extension, 217 patients were treated and 59.4% completed treatment. Both studies were terminated by the sponsor after a preplanned interim analysis indicated trial futility. At endpoint, the change from baseline in least-squares mean NRS pain scores in the intent-to-treat population was -2.04 for pregabalin versus -2.11 for placebo (P=.709). There were no significant differences between the pregabalin and placebo groups in the secondary efficacy measures. Incidence of adverse events was lower than seen in previous pregabalin studies. Overall, this trial did not show pregabalin to be more efficacious than placebo in treating HIV-associated DSP. Studies such as these, which fail to support their primary hypotheses, may be important in informing the methodology of future trials, especially when novel approaches to limit variability in the control group are included. ClinicalTrials.gov identifiers: NCT01049217 and NCT01145417.
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: david.simpson@mssm.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.affiliation: Pain Research, Department of Surgery and Cancer, Imperial College, London, UK; Pain Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
authors.forename: Andrew S C
authors.initials: AS
authors.lastname: Rice
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Birol
authors.initials: B
authors.lastname: Emir
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Jaren
authors.initials: J
authors.lastname: Landen
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Semel
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Marci L
authors.initials: ML
authors.lastname: Chew
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sporn
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D011115:Polyneuropathies / Q000188:drug therapy* / Q000209:etiology; D000069583:Pregabalin / Q000009:adverse effects / Q000627:therapeutic use*; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000700:Analgesics; D000069583:Pregabalin
keywords: HIV; Polyneuropathy; Pregabalin; Randomized controlled trial