Intranasal Fentanyl Spray Research Articles

Population pharmacokinetic metaanalysis of intranasal fentanyl spray as a means to enrich pharmacokinetic information for patients with cancer breakthrough pain

The development of intranasal fentanyl (INFS) aimed for a rapid treatment of breakthrough pain (BTP) in cancer patients. The pharmacokinetics (PK) of INFS was well characterized in healthy subjects, while PK investigations in cancer patients are limited. The objective was to develop a population PK model for fentanyl in volunteers and patients following INFS administration, to evaluate the influence of potential covariates and to simulate the exposure of fentanyl after repeated dosing in cancer patients. PK data from ten clinical trials were used for model development. The final model was validated with nonparametric bootstrap and visual predictive check. In addition, the secondary PK parameters (AUC0-tlast, Cmax, tmax) of a separate validation data set of INFS were predicted and compared to noncompartmental analysis results. Afterwards, repeated dose PK profiles in cancer patients were simulated. Plasma profiles after INFS administration were best described by a three-compartment model. Significant covariate relationships were identified for naltrexone and oxymetazoline co-treatment. Influences of body weight, BMI, sex and cancer patient as subject type were considered not to be clinically relevant. PK parameters for subpopulations of cancer patients were derived. Steady state simulations revealed that an extension from the current SmPC scenario to 6 pain episodes per day would yield similar Cmax values. A robust population PK model for INFS was developed. The model enhances the understanding of fentanyl PK after INFS dosing in cancer patients with BTP, a population for whom real-life data would be very hard to obtain.

Pharmacotherapy for Breakthrough Cancer Pain

Breakthrough pain (BTP) is a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain. The principal pharmacological treatment of BTP is represented by the administration of opioids as needed. Oral opioids have traditionally been the only available drugs for BTP. However, the onset and duration of action of oral opioids such as morphine or oxycodone may not be suitable for treating many episodes of BTP that are of short onset and duration. Transmucosal administration of lipophilic substances has gained a growing popularity in recent years due to the rapid effect, clinically observable 10-15 minutes after drug administration, and the non-invasive form. Different technologies have been developed to provide fast pain relief with potent opioid drugs such fentanyl, delivered by non-invasive routes (rapid onset opioids, ROOs). All the studies performed with ROOs have recommended that these drugs should be administered to opioid-tolerant patients receiving doses of oral morphine equivalents of at least 60 mg. These preparations, including oral transmucosal fentanyl citrate, fentanyl buccal tablet, sublingual fentanyl, intranasal fentanyl spray, fentanyl-pectin nasal spray and fentanyl buccal soluble film have shown better efficacy than placebo or oral opioids. Long-term studies have confirmed their efficacy and safety.

3057 POSTER The Efficacy of Intranasal Fentanyl Spray and Other Opioids for the Treatment of Breakthrough Cancer Pain

3057 POSTER The Efficacy of Intranasal Fentanyl Spray and Other Opioids for the Treatment of Breakthrough Cancer Pain

Newer Generation Fentanyl Transmucosal Products for Breakthrough Pain in Opioid-Tolerant Cancer Patients

Oral normal-release morphine has long been considered the gold-standard treatment for cancer breakthrough pain. However, its relatively long time to analgesic onset, delay in maximal analgesic effect and prolonged duration of action make it unsuitable for the management of breakthrough pain episodes. These limitations led to the development of an oral transmucosal formulation of the fast-acting opioid fentanyl (oral transmucosal fentanyl citrate [OTFC] lozenge on a plastic handle; Actiq®), which has been shown to produce more rapid and effective pain relief than oral morphine. However, the formulation itself has some limitations. Consequently, investigators have continued to develop other, newer generation, transmucosal formulations of fentanyl to further improve the management of breakthrough pain. Recently, five such compounds (Effentora®/Fentora®, Abstral®, Instanyl®, Breakyl®/OnsolisTM and PecFent®) have been concurrently approved in Europe and/or the US, and have documented efficacy in quickly relieving breakthrough pain episodes. All of the available pivotal efficacy trials of these agents are randomized, double-blind comparisons with placebo. There are no head-to-head trials comparing any of the newer transmucosal formulations with each other. Only one non-pivotal study of intranasal fentanyl spray used a transmucosal preparation as an active comparator. However, that comparator was OTFC, not one of the newer transmucosal products. Close examination of the existing trials assessing these newer transmucosal preparations reveals significant variation in many study parameters, such as patient selection criteria, severity of breakthrough pain episodes, proportions of patients with a neuropathic pain component, titration protocols, choice of the primary endpoints, protocols for repeat dosing and rescue medication, the separation of treated episodes and the extent of the placebo response, all of which may have affected efficacy results. It is therefore difficult to evaluate the relative efficacies of these treatments on the basis of the available trials. Furthermore, given the differences in design between studies, the value of any potential meta-analyses including these trials would likely be limited. Blinded head-to-head comparisons of new transmucosal fentanyl preparations would be the only way to conclusively determine comparative effectiveness, but given the impracticalities of conducting such studies, these are unlikely.

Fentanyl nasal spray for the treatment of cancer pain

Introduction: Breakthrough pain, a transitory flare of pain in patients with otherwise controlled chronic pain, has been well characterized in cancer patients but despite medical awareness, sometimes remains underdiagnosed and therefore undertreated.Areas covered: Oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablets are the first medications developed specifically for the treatment of breakthrough pain in opioid-tolerant patients. Since oral administration of fentanyl is not an option for many cancer patients, the development of intranasal fentanyl spray (INFS) emerged as a more effective method of administration. Intranasal administration of fentanyl has several advantages over the oral/gastrointestinal route and clinical trials have shown that it is superior to OTFC while being well tolerated and more acceptable by the majority of patients.Expert opinion: The aim of this review is to summarize the pharmacological characteristics and data obtained from clinical studies of INFS in the past few years, and present Fentanyl Pectin Nasal Spray (PecFent), which uses an innovative delivery system and is now approved in the EU. Finally, we discuss the impact that it may have in the future management of breakthrough pain in cancer patients, because an accurate diagnosis followed by the best treatment is crucial for effective pain alleviation.

Differences in rapid-acting opioid dosage forms for cancer-related BTP: a review of comparative effectiveness studies

Differences in rapid-acting opioid dosage forms for cancer-related BTP: a review of comparative effectiveness studies

An Economic Evaluation of Short-Acting Opioids for Treatment of Breakthrough Pain in Patients with Cancer

Objective Breakthrough cancer pain (BTCP) represents a considerable economic burden. A decision-analysis model was developed to evaluate the cost-effectiveness of intranasal fentanyl spray (INFS) compared with oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT) for the treatment of BTCP. Methods The model was parameterized for Sweden to estimate the costs and benefits associated with treatments. Expected reductions in pain intensity (PI; measured on a numeric rating scale ranging from 0 to 10) per BTCP episodes were translated into resource use and quality-adjusted life years (QALYs). Relative analgesic efficacy of interventions was derived from a mixed treatment comparison of six randomized controlled trials. The relationship between PI and utility was obtained from a time-trade off study in the general population. Resource use and unit cost data were obtained from the literature and validated by Swedish clinical experts. The base case scenario assumed three BTCP episodes/day, a background PI of 2, and a time horizon of 180 days. Prices of INFS and OTFC were assumed to be equal with FBT ∼14% less. Uncertainty in the source data was incorporated by probabilistic sensitivity analyses and different scenario analyses. Results With INFS, 55% of BTCP (95% uncertainty interval [UI]: 46–68%) was avoided, which is greater than expected with OTFC (29%; UI 22–38%) or FBT (31%; UI 25–39%). INFS was dominating OTFC (resulting in 0.046 QALY gain and saving 174 Euros with a time horizon of 180 days) and cost-effective versus FBT (incremental cost-effectiveness ratio 12203 Euros/QALY). Despite uncertainty in the source data, there is a >99% probability that INFS is the most cost-effective intervention. Conclusion Given inherent limitations of modelling studies, the greater efficacy of INFS translates to cost and QALY advantages over competing interventions in the treatment for BTCP in Sweden.

Intranasal fentanyl spray for breakthrough cancer pain: An innovative approach to the unmet needs

The treatment of breakthrough pain (BTP) in cancer patients is often sub-optimal. Normal-release oral opioid formulations have a slow onset of action, such that the episode of pain has often spontaneously subsided by the time the opioid starts to work. Other oral formulations, such as oral transmucosal fentanyl citrate (OTFC), may be associated with administration problems in many cancer patients who have salivary gland dysfunction or mucositis. Thus, there is the need for a treatment that matches a typical BTP episode and that is easy to use. Intranasal fentanyl spray (INFS) has been developed as a new route of administration with a fast onset of action. INFS has been investigated in four key clinical studies involving cancer patients with BTP. Pharmacokinetic analysis has shown a dose response for maximal plasma concentrations ( C max) of fentanyl and a short venous time to maximum plasma concentration ( T max). A dose-ranging efficacy study demonstrated a significant improvement in pain intensity difference (PID) over placebo from as early as 10 min post-administration. A later titrated-dose efficacy study supported these findings. In a head-to-head comparative trial between INFS and OTFC, significantly more patients achieved a faster onset of ‘meaningful’ pain relief with INFS than with OTFC, with INFS producing a significantly greater PID as early as 5 min post-dosing. Furthermore, a significantly higher proportion of patients preferred INFS over OTFC. In all clinical studies, including a 10-month follow-up, INFS was well tolerated. INFS should be considered a significant advance for the management of BTP.

Intranasal administration of opioids/fentanyl – Physiological and pharmacological aspects

Intranasal opioid formulations have been investigated as a new route of administration that may offer a rapid onset and short duration of analgesic effect. These characteristics are required for the optimal treatment of certain types of pain, e.g., breakthrough cancer pain, such that the temporal characteristics of the analgesic effect mirror those of the pain episode itself. The nasal cavity is highly perfused with permeable capillaries and is well suited for rapid drug uptake, however, challenges to intranasal administration are the small drug volume required to avoid run-off into the pharynx, and the short time window for absorption before the drug is removed from the nose via mucociliary clearance. Potent opioids, such as fentanyl, have the possibility of low administration volumes and are the best candidates for intranasal administration. Intranasal fentanyl spray (INFS) showed promising pharmacokinetic characteristics (such as a T max of 13 min) compared with other fentanyl formulations, and has a short duration of effect. These findings are supported by clinical evidence indicating that INFS is an effective treatment of breakthrough cancer pain, providing a rapid onset of analgesia, with a convenient method of administration.

Breakthrough cancer pain and current treatment options

Cancer patients with relatively stable chronic background pain may experience transient episodes of pain, known as breakthrough cancer pain (BTP). There is no universally accepted definition for BTP, although recent efforts have been made by the Association for Palliative Medicine of Great Britain and Ireland to refine existing definitions and diagnostic criteria. Common clinical features of a typical BTP episode include a rapid onset peaking within minutes, a severe intensity and a short duration. BTP affects patients’ quality of life through functional impairment and affective disturbances, and may also impact on healthcare resources through increased visits to physicians, hospitalisations due to pain, etc. As such, effective treatment is critical. Oral opioids are the mainstay of treatment for BTP. However, these are slow-acting with characteristics that do not match those of a typical BTP episode, and have the potential for over-medication and side effects. More favourable options would include treatments with a rapid onset, such as recently developed formulations of fentanyl, e.g., oral transmucosal fentanyl citrate (OTFC), buccal fentanyl citrate (FBT), and sublingual fentanyl citrate (SLF). However, these all require saliva/moisture to dissolve, potentially causing administration problems for cancer patients who commonly suffer from a dry mouth. The recently developed intranasal formulation of fentanyl (intranasal fentanyl spray) has a rapid onset and overcomes oral difficulties. It is a promising new option for the treatment of BTP.

Challenges in managing cancer pain

Effective pain control is a key factor in cancer management, and is primarily achieved through drug therapy. Despite the World Health Organization (WHO) guidelines for cancer pain management, many cancer patients still do not receive adequate analgesia. Lack of knowledge and misconceptions about opioid treatment is a key contributing factor, along with shortcomings in the WHO guidelines themselves. Evidence shows that starting treatment with strong opioids can provide significantly greater benefits than being treated according to the WHO recommended ‘analgesic ladder’ – a sequential escalation of treatment. There is, therefore, a need for alternative treatment strategies that optimise drug selection, dose and methods of administration. Although widely used, drug delivery through the oral routes is not always acceptable for cancer patients with oral and gastrointestinal problems, and as such a range of administration routes, including transdermal, transmucosal and intranasal routes should be considered. Promising clinical outcomes with treatments such as transdermal fentanyl and intranasal fentanyl spray lend support to the opinion that strong opioids, used in appropriate formulations and doses, play an important role in the care of patients with severe pain.

Efficacy of intranasal fentanyl spray versus other opioids for breakthrough pain in cancer

Objective:To compare the efficacy of intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC), fentanyl buccal tablet (FBT) and oral morphine (OM) for the treatment of breakthrough cancer pain (BTCP).Methods:A systematic literature review (Medline, EMBASE, BIOSIS; 1996–2007) identified six randomised controlled trials (RCTs) investigating the effects of INFS, OTFC, FBT and OM for the treatment of BTCP. The endpoint of interest was pain intensity difference (PID, reported on a 0–10 numeric rating scale [NRS]) up to 60 minutes after intake. Results of all trials were analysed simultaneously with a mixed treatment comparison (extended meta-analysis). MTC can be considered a valid method when included studies are comparable regarding effect modifying baseline patient and study characteristics.Results:INFS provided the greatest reduction in pain relative to placebo: PID 1.7 points (95% CrI: 1.4; 1.9) at 15 minutes, 2.0 (1.6; 2.3) at 30 minutes, 2.0 (1.5; 2.4) at 45 minutes and 1.9 (1.5; 2.4) at 60 minutes. PID for OTFC and FBT relative to placebo were 0.4 (0.0; 0.8) and 0.5 (0.3; 0.7) at 15 minutes. Both treatments provided a reduction in pain superior to placebo at other time points. INFS displayed a more than 99% probability of providing the greatest pain reduction out of all interventions compared at 15 minutes after intake. This was maintained for any measured time point before 45 minutes when compared to FBT and for any measured time point before 60 minutes when compared to OTFC. Only from 45 minutes onwards did OM show a greater pain reduction than placebo.Conclusion:Based on currently available evidence, INFS is expected to provide the greatest improvement in the treatment of BTCP. Due to its slow onset to effect OM cannot be considered an efficacious treatment for BTCP.

Pharmacokinetics of intranasal fentanyl spray in patients with cancer and breakthrough pain

This study reports the pharmacokinetics, tolerability, and safety of an intranasalfentanyl spray (INFS) in patients with cancer and breakthrough pain (BTP). A randomized, open-label, two-period, crossover trial. Nineteen adult patients (mean 57.8 years) with BTP, receiving opioid treatment for chronic background pain, from clinical departments in Austria, France, and Norway entered and completed the study. Patients were randomly assigned to receive one of six INFS dose sequences: 50/100, 100/50, 50/200, 200/50, 100/200, and 200/100 microg. INFS was administered as a single dose in one nostril. Each dose was separated by a minimum of 48 hours. Plasma fentanyl concentrations were measured by high-performance liquid chromatography and tandem mass spectrometry from blood samples obtained at 0 (predose) and frequently up to 300 minutes after INFS administration. Blood pressure, peripheral oxygen saturation, and respiratory rate were assessed eight times during each of the two treatment periods. Mean fentanyl plasma concentrations increased in a dose-dependent manner, peaking for all fentanyl doses 9-15 minutes after INFS administration. Median T(max) values were 15, 12, and 15 minutes for the 50, 100, and 200 microg doses of INFS, respectively. Mean (SD) values for C(max) were 351 (+/- 226), 595 (+/- 400), and 1195 (+/- 700) pg/mL, respectively, indicating dose-proportionality. Six patients (31.6 percent) experienced adverse events during the treatment period, the majority being mild in severity. INFS at doses of 50, 100, and 200 microg showed a short T(max) and was well tolerated in patients with cancer. These results support INFS use in patients with cancer suffering from BTP.

A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial

Objective:The efficacy of intranasal fentanyl spray (INFS) was compared with that of oral transmucosal fentanyl citrate (OTFC) for the relief of cancer-related breakthrough pain (BTP) in an open-label, crossover trial.Methods:Adult cancer patients receiving stable background opioid treatment and experiencing BTP episodes were recruited from 44 study centres in seven European countries (Austria, France, Germany, Italy, Poland, Spain and the United Kingdom); of the 196 patients enrolled, 139 were randomised to receive INFS followed by OTFC, or vice versa. Patients were titrated to an effective dose of one agent (50, 100 or 200 µg INFS; 200, 400, 600, 800, 1200 or 1600 µg OTFC) to treat six BTP episodes, then titration and treatment were repeated with the other agent. The primary outcome was patient-recorded time to onset of ‘meaningful’ pain relief. Secondary outcomes included pain intensity difference (PID) at 10 and 30 minutes (PID10, PID30), sum of PID at 15 and 60 minutes (SPID0–15, SPID0–60), ease of administration, treatment preference and relationship between background opioid dose and effective INFS dose. Additional outcome measures included proportions of episodes with ≥33% and ≥50% pain intensity (PI) reduction, and PID at additional time points.Clinical trial registration number:NCT00496392.Results:Among the intention-to-treat population (n = 139), median time to onset of ‘meaningful’ pain relief was 11 minutes with INFS versus 16 minutes with OTFC; 65.7% of patients attained faster time to ‘meaningful’ pain-relief onset with INFS (p < 0.001). PID was statistically significantly greater for INFS than OTFC from 5 minutes post-dosing. Significantly more INFS-treated breakthrough pain episodes achieved clinically important pain relief (≥33% and ≥50% PI reduction) up to 30 minutes post-dosing. The proportions of episodes treated with INFS and OTFC achieving a PI reduction of ≥33% at 5 minutes were 25.3% versus 6.8% (p < 0.001), and at 10 minutes were 51.0% versus 23.6% (p < 0.001), respectively; the proportions of episodes treated with INFS and OTFC achieving a ≥50% PI reduction at 5 minutes were 12.8% versus 2.1% (p < 0.001), and at 10 minutes were 36.9% versus 9.7% (p < 0.001), respectively. Higher SPID0–15 and SPID0–60 scores were achieved with INFS (p < 0.001). More patients preferred INFS than OTFC (p < 0.001) and more patients found it very easy/easy to use. Both treatments were well tolerated. In the safety population (n = 139), 56.8% (n = 79) of patients experienced ≥1 AE during the trial. The only AE that occurred in ≥5% of patients in either treatment group was nausea. Among those patients who experienced serious AEs (13.7%, n = 19), none were considered to be related to either study medication. There was a weak correlation between effective INFS doses and background opioid doses.Conclusion:In this open-label, randomised, crossover trial, significantly more patients attained faster ‘meaningful’ pain relief with INFS than OTFC, and more patients preferred INFS to OTFC.

4256 Qol in correlation with access to chemotherapy: phase III NGO project on supportive care efforts by an Indian NGO

Cancer patients with relatively stable chronic background pain may experience transient episodes of pain, known as breakthrough cancer pain (BTP). There is no universally accepted definition for BTP, although recent efforts have been made by the Association for Palliative Medicine of Great Britain and Ireland to refine existing definitions and diagnostic criteria. Common clinical features of a typical BTP episode include a rapid onset peaking within minutes, a severe intensity and a short duration. BTP affects patients’ quality of life through functional impairment and affective disturbances, and may also impact on healthcare resources through increased visits to physicians, hospitalisations due to pain, etc. As such, effective treatment is critical. Oral opioids are the mainstay of treatment for BTP. However, these are slow-acting with characteristics that do not match those of a typical BTP episode, and have the potential for over-medication and side effects. More favourable options would include treatments with a rapid onset, such as recently developed formulations of fentanyl, e.g., oral transmucosal fentanyl citrate (OTFC), buccal fentanyl citrate (FBT), and sublingual fentanyl citrate (SLF). However, these all require saliva/moisture to dissolve, potentially causing administration problems for cancer patients who commonly suffer from a dry mouth. The recently developed intranasal formulation of fentanyl (intranasal fentanyl spray) has a rapid onset and overcomes oral difficulties. It is a promising new option for the treatment of BTP.

717 HIGHER SYSTEMIC BIOAVAILABILITY AND FASTER ABSORPTION OF INTRANASAL FENTANYL SPRAY (INFS) COMPARED TO ACTIQ® (OTFC) IN HEALTHY SUBJECTS

European Journal of PainVolume 13, Issue S1 p. S206b-S207 717 HIGHER SYSTEMIC BIOAVAILABILITY AND FASTER ABSORPTION OF INTRANASAL FENTANYL SPRAY (INFS) COMPARED TO ACTIQ® (OTFC) IN HEALTHY SUBJECTS R. Nave, Nycomed GmbH, Konstanz, GermanySearch for more papers by this authorE.H. Sides, AAI Pharma, Morrrisville, United StatesSearch for more papers by this authorT. Colberg, Nycomed, Roskilde, DenmarkSearch for more papers by this authorSø. Lophaven, Nycomed, Roskilde, DenmarkSearch for more papers by this authorX. Meng, Hurley Consulting Associates Ltd., Chatham, United StatesSearch for more papers by this authorG. Lahu, Nycomed GmbH, Konstanz, GermanySearch for more papers by this authorH. Schmitt, Nycomed GmbH, Konstanz, GermanySearch for more papers by this author R. Nave, Nycomed GmbH, Konstanz, GermanySearch for more papers by this authorE.H. Sides, AAI Pharma, Morrrisville, United StatesSearch for more papers by this authorT. Colberg, Nycomed, Roskilde, DenmarkSearch for more papers by this authorSø. Lophaven, Nycomed, Roskilde, DenmarkSearch for more papers by this authorX. Meng, Hurley Consulting Associates Ltd., Chatham, United StatesSearch for more papers by this authorG. Lahu, Nycomed GmbH, Konstanz, GermanySearch for more papers by this authorH. Schmitt, Nycomed GmbH, Konstanz, GermanySearch for more papers by this author First published: 12 January 2012 https://doi.org/10.1016/S1090-3801(09)60720-5Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume13, IssueS1September 2009Pages S206b-S207 RelatedInformation

4254 Efficacy and patient preference for intranasal fentanyl spray (INFS) versus oral transmucosal fentanyl citrate (OTFC) for breakthrough cancer pain – an open-label crossover trial

4254 Efficacy and patient preference for intranasal fentanyl spray (INFS) versus oral transmucosal fentanyl citrate (OTFC) for breakthrough cancer pain – an open-label crossover trial

684 TITRATION OF INTRANASAL FENTANYL SPRAY (INFS) FOR BREAKTHROUGH PAIN IN CANCER PATIENTS: EVIDENCE FOR DOSE PROPORTIONALITY VS BACKGROUND ANALGESIA

European Journal of PainVolume 13, Issue S1 p. S197c-S197 684 TITRATION OF INTRANASAL FENTANYL SPRAY (INFS) FOR BREAKTHROUGH PAIN IN CANCER PATIENTS: EVIDENCE FOR DOSE PROPORTIONALITY VS BACKGROUND ANALGESIA H.G. Kress, H.G. Kress Medical University/AKH Vienna, Vienna, AustriaSearch for more papers by this authorT. Colberg, T. Colberg Nycomed, Roskilde, DenmarkSearch for more papers by this author H.G. Kress, H.G. Kress Medical University/AKH Vienna, Vienna, AustriaSearch for more papers by this authorT. Colberg, T. Colberg Nycomed, Roskilde, DenmarkSearch for more papers by this author First published: 12 January 2012 https://doi.org/10.1016/S1090-3801(09)60687-XCitations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume13, IssueS1September 2009Pages S197c-S197 RelatedInformation

720 PHARMACOKINETICS AFTER ADMINISTRATION OF 100 μG INTRANASAL FENTANYL SPRAY (1 DOSE VS. 2 DOSES) IN NON-ELDERLY AND ELDERLY HEALTHY SUBJECTS

European Journal of PainVolume 13, Issue S1 p. S207b-S208 720 PHARMACOKINETICS AFTER ADMINISTRATION OF 100 μG INTRANASAL FENTANYL SPRAY (1 DOSE VS. 2 DOSES) IN NON-ELDERLY AND ELDERLY HEALTHY SUBJECTS R. Nave, R. Nave Nycomed GmbH, Konstanz, GermanySearch for more papers by this authorE.H. Sides, E.H. Sides AAI Pharma, Morrrisville, United StatesSearch for more papers by this authorT. Colberg, T. Colberg Nycomed, Roskilde, DenmarkSearch for more papers by this authorX. Meng, X. Meng Hurley Consulting Associates Ltd., Chatham, United StatesSearch for more papers by this authorG. Lahu, G. Lahu Nycomed GmbH, Konstanz, GermanySearch for more papers by this authorH. Schmitt, H. Schmitt Nycomed GmbH, Konstanz, GermanySearch for more papers by this author R. Nave, R. Nave Nycomed GmbH, Konstanz, GermanySearch for more papers by this authorE.H. Sides, E.H. Sides AAI Pharma, Morrrisville, United StatesSearch for more papers by this authorT. Colberg, T. Colberg Nycomed, Roskilde, DenmarkSearch for more papers by this authorX. Meng, X. Meng Hurley Consulting Associates Ltd., Chatham, United StatesSearch for more papers by this authorG. Lahu, G. Lahu Nycomed GmbH, Konstanz, GermanySearch for more papers by this authorH. Schmitt, H. Schmitt Nycomed GmbH, Konstanz, GermanySearch for more papers by this author First published: 12 January 2012 https://doi.org/10.1016/S1090-3801(09)60723-0Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume13, IssueS1September 2009Pages S207b-S208 RelatedInformation

Efficacy and tolerability of intranasal fentanyl spray 50 to 200 μg for breakthrough pain in patients with cancer: A phase III, multinational, randomized, double-blind, placebo-controlled, crossover trial with a 10-month, open-label extension treatment period

Objective: This trial investigated the efficacy and long-term tolerability of intranasal fentanyl spray (INFS) 50 to 200 μg in the treatment of breakthrough pain in opioid-tolerant patients with cancer. Methods: This Phase III, double-blind, randomized, placebo-controlled, crossover trial was conducted at pain centers, anesthesiology departments, palliative care units, and oncology clinics in Austria, Denmark, France, Germany, and Poland. Eligible patients were adults with cancer receiving a stable dose of long-term opioid treatment for the control of background pain. Patients were treated at home with their effective dose of INFS (50, 100, or 200 μg) or inactive spray (placebo) in a randomized sequence for 3 weeks, followed by a 10-month, open-label tolerability phase during which they received their effective dose of INFS. Throughout the study, patients were allowed to use their usual rescue medication, which was recorded in patient diaries. The primary efficacy end point was the pain intensity difference at 10 minutes after study drug administration (PID 10), as assessed using an 11-point numeric rating scale (0 = no pain to 10 = worst pain imaginable). An effect size of 0.5 for PID was considered clinically relevant. The rate of response, defined as PID 10 >2, was also assessed. Adverse events (AEs) were recorded in patient diaries during the efficacy period and reported in monthly clinic visits and follow-up weekly telephone contacts during the extension period. Results: In all, 120 patients were enrolled and achieved an effective dose; 113 were randomized and 111 were included in the intent-to-treat analysis set (56 men, 55 women; mean [SD] age, 60.6 [9.45] years; mean weight, 70.3 kg [men] and 65.3 kg [women]; white race, 107 [96.4%]; INFS 50 μg, 18; INFS 100 μg, 48; INFS 200 μg, 45; placebo, 110). PID 10 with INFS was 2-fold that with placebo (adjusted means, 2.36 vs 1.10; adjusted difference, 1.26 [greater than the clinically relevant difference of 0.5]; P < 0.001). Additional analysis revealed that the mean response rate with all 3 doses of INFS was 51.1% versus 20.9% with placebo. The prevalence of AEs was 22/111 (19.8%) during the efficacy period, during which the most frequently reported AEs were nausea (5 [4.5%]) and vertigo (2 [1.8%]). No serious AEs were considered related to the study drugs. In all, 108 patients entered the extension period, with a mean duration of exposure to INFS of 134.9 days. Progression of underlying malignant disease was the most common AE reported during this period (55 [50.9%]); this event was not considered treatment related. Conclusions: In these opioid-tolerant patients with cancer, INFS at doses of 50, 100, and 200 μg was associated with an onset of activity at 10 minutes and effective treatment of breakthrough pain compared with placebo. All doses were generally well tolerated and clinically efficacious.