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S609 PRELIMINARY GERMAN DATA FROM A EUROPEAN OPEN-LABEL MULTICENTRE STUDY IN BREAKTHROUGH CANCER PAIN PATIENTS TREATED WITH FENTANYL BUCCAL TABLET (FBT)
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POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
Results: Optimal anaesthesia and analgesia for foot and ankle surgery were obtained in all patients. No complications were reported. Conclusions: The results achieved have been encouraging, leading us to propose this new point as an efficient approach in foot surgery or an alternative to other techniques. Disclosure: None declared
S609 PRELIMINARY GERMAN DATA FROM A EUROPEAN OPEN-LABEL MULTICENTRE STUDY IN BREAKTHROUGH CANCER PAIN PATIENTS TREATED WITH FENTANYL BUCCAL TABLET (FBT) W. Meissner1 *, A. Schwittay2 , E. Lux3 , U.R. Kleeberg4 , H. Schneid5 . 1 Friedrich-Schiller-University, Jena, 2 Praxis Dr. Andreas Schwittay, B¨ ohlen, 3 Klinikum St.-Marien-Hospital, L¨ unen, 4 H¨ ametologischOnkologische Praxis Altona (HOPA), Hamburg, Germany; 5 Cephalon, Maisons-Alfort, France Background: FBT treats adult patients with breakthrough cancer pain (BTcP) receiving opioid maintenance therapy and should be titrated to a successful dose. This study compares FBT effective dose starting titration at 100 mg vs 200 mg. Secondary objectives evaluates efficacy and safety. Here are German preliminary data. Methods: After the screening period, patients were enrolled in an open-label randomized titration period (100 or 200 mg) up to a successful dose (100, 200, 400, 600, 800 mg), followed by an openlabel treatment period (8 BTcP episodes). The inclusion criteria followed FBT SmPC. This analysis provides baseline characteristics and patients’ assessment. Results: Patients enrolled (n = 90) were mainly out-patients (70%, 63/90). Breast cancer was the most frequent primary tumour (26.7%). Maintenance opioid therapy was: transdermal fentanyl 43.5%, hydromorphone 20.7%, oxycodone 20.7%, oral morphine 10.9%, other opioid 10.9%, and with a mean overall pain intensity = 5.4±2.4, 0–10 NS. At baseline 71.8% (56/78) of the patients reported 1–3 episodes per day. The average time from onset to peak intensity was within 10 minutes for 48.7% of the patients (38/78), 10–30 for 38.5% (30/78) and >30 minutes for 12.8% (10/78). After titration, the 200 mg strength was the most common successful FBT dose (42%). FBT was assessed as very easy-easy for treating BTcP (72.7%, 32/44). The patient satisfaction was in favour of FBT. Conclusions: These preliminary data on BTcP episodes characterization are consistent with previous published studies. The majority of the patients found FBT convenient to use. Further results will provide information in clinical practice from several European countries. Disclosure: 5 HSchneid Cephalon employers
S610 SINGLE-DOSE AND MULTI-DOSE DELIVERY SYSTEMS FOR INTRANASAL FENTANYL SPRAY ARE BIOEQUIVALENT R. Nave1 *, S. Lophaven2 , L. Popper2 , G. Lahu1 , H. Schmitt1 . 1 Nycomed, Konstanz, Germany; 2 Nycomed, Roskilde, Denmark Background and Aims: Intranasal fentanyl spray (INFS) was developed to treat patients with Breakthrough Cancer Pain. INFS is delivered via a multi-dose delivery system (MDS) that is available in dose strengths of 50, 100 and 200 mg. The aim of this study was to demonstrate the pharmacokinetic bioequivalence of INFS single dose delivery system (SDS) in relation to the currently marketed MDS device. Methods: In a randomised, single-centre, single-dose, open label, comparative, four-period, two-sequence, replicate cross-over study 48 healthy subjects (24 males, 24 females, mean age 28.1 years) received 200 mg/100 ml fentanyl administered via SDS and via MDS in one of two alternating treatment sequences. Naltrexone was given to prevent potential adverse reactions from fentanyl administration. Frequent plasma samples were taken and analysed
by LC-MS/MS. Primary pharmacokinetic parameters were AUC0−inf and Cmax , which were analysed using a linear mixed effect model applied to the natural log-transformed data. Results: Healthy subjects showed very similar plasma concentration over time profiles for both delivery systems. The mean fentanyl Cmax and AUC0−inf values for SDS and MDS were 948 pg/ml, 949 pg/ml and 4439 pg×h/ml, 4489 pg×h/ml. respectively. Point estimates (90% confidence intervals) for AUC and Cmax were 0.97 (0.93–1.02) and 1.00 (0.92–1.09) and therefore in the bioequivalence range of 0.80–1.25. Conclusions: Results of this study show that SDS and MDS met the pre-defined regulatory criteria for bioequivalence. Safety profiles were consistent between both devices and INFS administered in combination with naltrexone was well tolerated. Disclosure: All authors are employees of Nycomed involved in the development of Instanyl
S611 NO APPARENT DIFFERENCES IN PHARMACOKINETICS OF INTRANASAL FENTANYL SPRAY INVESTIGATING NASAL-DRIPPING AFTER ADMINISTRATING UP TO 400 mL PER NOSTRIL R. Nave1 *, L. Popper2 , G. Lahu1 , H. Schmitt1 . 1 Nycomed, Konstanz, Germany; 2 Nycomed, Roskilde, Denmark Background and Aims: Intranasal Fentanyl Spray (INFS) was developed in different dose strengths for the treatment of breakthrough pain in cancer patients. The primary objective was to assess a potential volume effect when exceeding the recommended spray volume per nostril on pharmacokinetic profiles of INFS in healthy subjects. Methods: In a randomised, single-centre, open-label, 4-way crossover pharmacokinetic study, 12 healthy subjects (mean age 24.4 years, mean BMI 23.8 kg/m2 ) pre-emptively treated with naltrexone, received 1, 2, 3, or 4 doses of INFS 50 mg/100 ml via a single-dose delivery system in one nostril. Frequent plasma samples were taken up to 72 hours and analysed by LC-MS/MS. Primary pharmacokinetic parameters were AUC0−inf and Cmax . Results: Fentanyl was absorbed rapidly following administration of INFS. Dose-dependent increases of Cmax and AUC were observed with increasing total doses and volumes of 50 mg/100 ml INFS (100, 200, 300, and 400 ml respectively). After careful visual inspection some nasal dripping from the nostril was observed in 7 of the 12 subjects, and was mostly observed after administration of INFS 400 ml. However, mean Cmax and AUC still demonstrated a dosedependent increase with increasing volume. Conclusions: In summary, there was no apparent volume effect across the investigated INFS doses and volumes on dose-normalized AUC0−inf and Cmax results. A favorable nasal tolerability profile was observed. Although some nasal dripping was present at higher volumes, there was no effect on the overall systemic exposure of fentanyl. The INFS/naltrexone combination showed a tolerable safety profile. Disclosure: All authors are employees of Nycomed involved in the development of Instanyl.
S612 UTILITY AND APPLICATION OF INSTANYL® POPULATION PHARMACOKINETIC METAANALYSIS FOR RATIONAL MANAGEMENT OF BREAKTHROUGH CANCER PAIN N. Kaessner, R. Nave *, S. Roepcke, A. Facius, G. Lahu. Nycomed, Konstanz, Germany Background and Aims: Intranasal fentanyl spray (Instanyl® ) was developed to treat patients with breakthrough cancer pain. Pharmacokinetic (PK) investigations with Instanyl® in cancer patients are limited. The objective of the investigation was to develop a population (Pop) PK model on all available PK data to provide a sound PK knowledge basis for cancer patients.
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
Results: Optimal anaesthesia and analgesia for foot and ankle surgery were obtained in all patients. No complications were reported. Conclusions: The results achieved have been encouraging, leading us to propose this new point as an efficient approach in foot surgery or an alternative to other techniques. Disclosure: None declared
S609 PRELIMINARY GERMAN DATA FROM A EUROPEAN OPEN-LABEL MULTICENTRE STUDY IN BREAKTHROUGH CANCER PAIN PATIENTS TREATED WITH FENTANYL BUCCAL TABLET (FBT) W. Meissner1 *, A. Schwittay2 , E. Lux3 , U.R. Kleeberg4 , H. Schneid5 . 1 Friedrich-Schiller-University, Jena, 2 Praxis Dr. Andreas Schwittay, B¨ ohlen, 3 Klinikum St.-Marien-Hospital, L¨ unen, 4 H¨ ametologischOnkologische Praxis Altona (HOPA), Hamburg, Germany; 5 Cephalon, Maisons-Alfort, France Background: FBT treats adult patients with breakthrough cancer pain (BTcP) receiving opioid maintenance therapy and should be titrated to a successful dose. This study compares FBT effective dose starting titration at 100 mg vs 200 mg. Secondary objectives evaluates efficacy and safety. Here are German preliminary data. Methods: After the screening period, patients were enrolled in an open-label randomized titration period (100 or 200 mg) up to a successful dose (100, 200, 400, 600, 800 mg), followed by an openlabel treatment period (8 BTcP episodes). The inclusion criteria followed FBT SmPC. This analysis provides baseline characteristics and patients’ assessment. Results: Patients enrolled (n = 90) were mainly out-patients (70%, 63/90). Breast cancer was the most frequent primary tumour (26.7%). Maintenance opioid therapy was: transdermal fentanyl 43.5%, hydromorphone 20.7%, oxycodone 20.7%, oral morphine 10.9%, other opioid 10.9%, and with a mean overall pain intensity = 5.4±2.4, 0–10 NS. At baseline 71.8% (56/78) of the patients reported 1–3 episodes per day. The average time from onset to peak intensity was within 10 minutes for 48.7% of the patients (38/78), 10–30 for 38.5% (30/78) and >30 minutes for 12.8% (10/78). After titration, the 200 mg strength was the most common successful FBT dose (42%). FBT was assessed as very easy-easy for treating BTcP (72.7%, 32/44). The patient satisfaction was in favour of FBT. Conclusions: These preliminary data on BTcP episodes characterization are consistent with previous published studies. The majority of the patients found FBT convenient to use. Further results will provide information in clinical practice from several European countries. Disclosure: 5 HSchneid Cephalon employers
S610 SINGLE-DOSE AND MULTI-DOSE DELIVERY SYSTEMS FOR INTRANASAL FENTANYL SPRAY ARE BIOEQUIVALENT R. Nave1 *, S. Lophaven2 , L. Popper2 , G. Lahu1 , H. Schmitt1 . 1 Nycomed, Konstanz, Germany; 2 Nycomed, Roskilde, Denmark Background and Aims: Intranasal fentanyl spray (INFS) was developed to treat patients with Breakthrough Cancer Pain. INFS is delivered via a multi-dose delivery system (MDS) that is available in dose strengths of 50, 100 and 200 mg. The aim of this study was to demonstrate the pharmacokinetic bioequivalence of INFS single dose delivery system (SDS) in relation to the currently marketed MDS device. Methods: In a randomised, single-centre, single-dose, open label, comparative, four-period, two-sequence, replicate cross-over study 48 healthy subjects (24 males, 24 females, mean age 28.1 years) received 200 mg/100 ml fentanyl administered via SDS and via MDS in one of two alternating treatment sequences. Naltrexone was given to prevent potential adverse reactions from fentanyl administration. Frequent plasma samples were taken and analysed
by LC-MS/MS. Primary pharmacokinetic parameters were AUC0−inf and Cmax , which were analysed using a linear mixed effect model applied to the natural log-transformed data. Results: Healthy subjects showed very similar plasma concentration over time profiles for both delivery systems. The mean fentanyl Cmax and AUC0−inf values for SDS and MDS were 948 pg/ml, 949 pg/ml and 4439 pg×h/ml, 4489 pg×h/ml. respectively. Point estimates (90% confidence intervals) for AUC and Cmax were 0.97 (0.93–1.02) and 1.00 (0.92–1.09) and therefore in the bioequivalence range of 0.80–1.25. Conclusions: Results of this study show that SDS and MDS met the pre-defined regulatory criteria for bioequivalence. Safety profiles were consistent between both devices and INFS administered in combination with naltrexone was well tolerated. Disclosure: All authors are employees of Nycomed involved in the development of Instanyl
S611 NO APPARENT DIFFERENCES IN PHARMACOKINETICS OF INTRANASAL FENTANYL SPRAY INVESTIGATING NASAL-DRIPPING AFTER ADMINISTRATING UP TO 400 mL PER NOSTRIL R. Nave1 *, L. Popper2 , G. Lahu1 , H. Schmitt1 . 1 Nycomed, Konstanz, Germany; 2 Nycomed, Roskilde, Denmark Background and Aims: Intranasal Fentanyl Spray (INFS) was developed in different dose strengths for the treatment of breakthrough pain in cancer patients. The primary objective was to assess a potential volume effect when exceeding the recommended spray volume per nostril on pharmacokinetic profiles of INFS in healthy subjects. Methods: In a randomised, single-centre, open-label, 4-way crossover pharmacokinetic study, 12 healthy subjects (mean age 24.4 years, mean BMI 23.8 kg/m2 ) pre-emptively treated with naltrexone, received 1, 2, 3, or 4 doses of INFS 50 mg/100 ml via a single-dose delivery system in one nostril. Frequent plasma samples were taken up to 72 hours and analysed by LC-MS/MS. Primary pharmacokinetic parameters were AUC0−inf and Cmax . Results: Fentanyl was absorbed rapidly following administration of INFS. Dose-dependent increases of Cmax and AUC were observed with increasing total doses and volumes of 50 mg/100 ml INFS (100, 200, 300, and 400 ml respectively). After careful visual inspection some nasal dripping from the nostril was observed in 7 of the 12 subjects, and was mostly observed after administration of INFS 400 ml. However, mean Cmax and AUC still demonstrated a dosedependent increase with increasing volume. Conclusions: In summary, there was no apparent volume effect across the investigated INFS doses and volumes on dose-normalized AUC0−inf and Cmax results. A favorable nasal tolerability profile was observed. Although some nasal dripping was present at higher volumes, there was no effect on the overall systemic exposure of fentanyl. The INFS/naltrexone combination showed a tolerable safety profile. Disclosure: All authors are employees of Nycomed involved in the development of Instanyl.
S612 UTILITY AND APPLICATION OF INSTANYL® POPULATION PHARMACOKINETIC METAANALYSIS FOR RATIONAL MANAGEMENT OF BREAKTHROUGH CANCER PAIN N. Kaessner, R. Nave *, S. Roepcke, A. Facius, G. Lahu. Nycomed, Konstanz, Germany Background and Aims: Intranasal fentanyl spray (Instanyl® ) was developed to treat patients with breakthrough cancer pain. Pharmacokinetic (PK) investigations with Instanyl® in cancer patients are limited. The objective of the investigation was to develop a population (Pop) PK model on all available PK data to provide a sound PK knowledge basis for cancer patients.