BackgroundCombination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective.MethodsThis was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours.Results606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable.ConclusionsDexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae.Trial registrationEudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).Electronic supplementary materialThe online version of this article (doi:10.1186/s10194-015-0541-5) contains supplementary material, which is available to authorized users.

Purpose To determine whether abagovomab maintenance therapy prolongs recurrence-free (RFS) and overall survival (OS) in patients with ovarian cancer in first clinical remission. Patients and Methods Patients with International Federation of Gynecology and Obstetrics stage III to IV ovarian cancer in complete clinical remission after primary surgery and platinum- and taxane-based chemotherapy were randomly assigned at a ratio of 2:1 in a phase III, double-blind, placebo-controlled, multicenter study. Abagovomab 2 mg or placebo was administered as 1-mL suspension once every 2 weeks for 6 weeks (induction phase) and then once every 4 weeks (maintenance phase) until recurrence or up to 21 months after random assignment of the last patient. The primary end point was RFS; secondary end points were OS and immunologic response. Results Characteristics of the 888 patients included: mean age, 56.3 years; Eastern Cooperative Oncology Group performance status, ≤ 1 in > 99% of patients; serous papillary subtype, 81.5%; stage III, 85.9%; and cancer antigen 125 ≤ 35U/mL after third cycle, 80.9%. Mean exposure to study treatment (± standard deviation) was 449.7 ± 333.08 days. Hazard ratio (HR) of RFS for the treatment group using tumor size categorization (≤ 1 cm, > 1 cm) was 1.099 (95% CI, 0.919 to 1.315; P = .301). HR of OS using tumor size categorization (≤ 1 cm, > 1 cm) was 1.150 (95% CI, 0.872 to 1.518; P = .322). The most frequently reported type of adverse event was an injection site reaction in 445 patients (50.2%), followed by injection site erythema and fatigue in 227 (25.6%) and 212 patients (23.9%), respectively. By the final visit, median anti–anti-idiotypic antibody level was 493,000.0 ng/mL, indicating a robust response. Conclusion Abagovomab administered as repeated monthly injections is safe and induces a measurable immune response. Administration as maintenance therapy for patients with ovarian cancer in first remission does not prolong RFS or OS.

BackgroundDexketoprofen trometamol plus tramadol hydrochloride is a new oral combination of two analgesics, which have different mechanisms of action for the treatment of moderate to severe acute pain.MethodsRandomised, double-blind, parallel, placebo and active-controlled, single and multiple-dose study to evaluate the analgesic efficacy and safety of dexketoprofen/tramadol 25 mg/75 mg in comparison with the single agents (dexketoprofen 25 mg and tramadol 100 mg) in moderate to severe acute pain after abdominal hysterectomy.Patients received seven consecutive doses of study drug within a 3-day period, each dose separated by an 8-hour interval. A placebo arm was included during the single-dose phase to validate the pain model.Efficacy assessments included pain intensity, pain relief, patient global evaluation and use of rescue medication. The primary endpoint was the mean sum of pain intensity differences over the first 8 h (SPID8).ResultsThe efficacy analysis included 606 patients, with a mean age of 48 years (range 25–73). The study results confirmed the superiority of the combination over the single agents in terms of the primary endpoint (p <0.001). Secondary endpoints were generally supportive of the superiority of the combination for both single and multiple doses.Most common adverse drug reactions (ADRs) were nausea (4.6 %) and vomiting (2.3 %). All other ADRs were experienced by less than 2 % of patients.ConclusionsThe study results provided robust evidence of the superiority of dexketoprofen/tramadol 25 mg/75 mg over the single components in the management of moderate to severe acute pain, as confirmed by the single-dose efficacy, repeated-dose sustained effect and good safety profile observed.Trial registrationEU Clinical Trials Register (EudraCT number 2012-004545-32, registered 04 October 2012); Clinicaltrials.gov (NCT01904149, registered 17 July 2013).Electronic supplementary materialThe online version of this article (doi:10.1186/s12871-016-0174-5) contains supplementary material, which is available to authorized users.