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(189) Rapid and effective control of breakthrough pain (BTP) and tolerability in cancer patients treated with BEMA (BioErodible MucoAdhesive) fentanyl
Abstracts (188) Total freedom from cancer pain at a tertiary cancer centre in India—A retrospective analysis of 3238 patients S Bhatnagar; All India Institute of Medical Sciences, New Delhi, India Effective pain control is essential for the management of patients with cancer. About 70-80% of patients with cancer present in an advanced stage of disease. Patients with advanced cancer frequently experience intractable pain with diverse symptoms that can make daily living impossible and affect the quality of life. This paper reports the management of 3238 patients with cancer pain over a period of five years. Nearly 89.6% patients had good pain relief, with VAS less than 3. These promising results were achieved by careful patient assessment, close liaison with clinicians from other specialties and by using a variety of analgesic regimen including oral analgesics, anaesthetic procedures, psychological interventions and supportive care. However, the main stay of treatment was oral analgesics, according to the principles of WHO analgesic ladder.
P23 (190) The safety of BEMA (BioErodible MucoAdhesive) fentanyl use for breakthrough pain (BTP) in cancer patients N Slatkin, W Hill, A Finn; City of Hope, Department of Supportive Care, Pain and Palliative Medicine, Duarte, CA The BEMA drug delivery system was designed to improve oral transmucosal dosing reliability, tolerability, and patient acceptance. The mucoadhesive polymers adhere and deliver fentanyl across the capillary rich mucosa. Two-hundred twenty (220) adult opioid-tolerant patients with chronic cancer pain who experienced one to four daily episodes of BTP while on stable opioid doses (i.e., a daily dose equal in analgesic activity to at least 60 mg of oral morphine) received BEMA fentanyl in an openlabel, multicenter study. Patients were titrated to an effective dose and then continued with dosage adjustment as required. The initial effective dose was ⱕ1200 g in 94.3% of subjects entering the Open-label Period. Administration of the initial 200 g dose of BEMA fentanyl to 97/220 subjects was monitored by study personnel; none of the subjects experienced AEs. Patients received, on average, 2.9 doses per day for 111.9 days (maximum exposure duration of 531 days). The most frequently reported AEs attributed to study drug were nausea (8.6%), dizziness (5.5%), constipation (5.0%), and somnolence (4.5%); these four AEs were also the only AEs that appeared to be dose-related (during the Titration Period only). Although more than 56,000 episodes of BTP were treated with BEMA fentanyl in this study, only one case of respiratory depression was reported, an event not attributed to study drug. There were no deaths attributed to study drug. There was no relationship between the incidence of AEs and age, gender or race. Three (1.4%) subjects experienced mild stomatitis that was possibly related to BEMA fentanyl; none resulted in study drug discontinuation. The AE profile of BEMA fentanyl was consistent with the use of an opioid in patients with cancer and chronic pain. Research supported by BioDelivery Sciences International.
(189) Rapid and effective control of breakthrough pain (BTP) and tolerability in cancer patients treated with BEMA (BioErodible MucoAdhesive) fentanyl
(191) Dose linearity and absolute bioavailability of BEMA (BioErodible MucoAdhesive) fentanyl in healthy volunteers
J North, R Kapoor, J Bull, W Reid, A Finn; Carolinas Pain Institute, WinstonSalem, NC Transmucosal delivery of fentanyl can provide prompt control of BTP in patients taking stable doses of opioids for chronic pain.1,2 The BEMA drug delivery system was designed to improve transmucosal dosing reliability, tolerability, and patient acceptance. BEMA Fentanyl consists of a small unit that is placed against the oral mucosa. The mucoadhesive polymers adhere to the membrane and deliver fentanyl across the capillary rich mucosa. Eighty adult cancer patients on stable opioid doses who achieved adequate control of BTP with BEMA fentanyl (200 to 1200 g) in an open-label titration phase were treated for up to 9 BTP episodes with the previously determined BEMA fentanyl dose (6 episodes) and placebo (3 episodes) in a double-blind random sequence. Subjects recorded pain intensity (PI; 11-point scale) at the time of treatment, and at 5, 10, 15, 30, 45, and 60 minutes after treatment. The primary outcome measure was the sum of PI differences (SPID) at 30 minutes. A total of 394 BTP episodes were treated with BEMA fentanyl and 197 with placebo. Of the patients who entered the study, only 3.3% of patients withdrew for lack of effective pain relief in the titration phase. SPID values for BEMA fentanyl-treated episodes were statistically significantly greater than placebo-treated episodes at 15 minutes (12.7⫾0.88 vs. 10.6⫾1.06; p⫽0.047), 30 minutes (49.1⫾2.40 vs. 39.0⫾2.95, p⫽0.004), and through 60 minutes. The most commonly reported treatment-related adverse events were somnolence (6.0%), nausea (5.3%), dizziness (4.6%), and vomiting (4.0%), which are commonly associated with opioid use. There were no reports of treatment-related mucositis or respiratory depression during the study. BEMA fentanyl provided patients with a rapid, effective, and convenient means to control cancer BTP with a favorable tolerability profile. Research supported by BioDelivery Sciences International (1. Farrar, JNCI,1998; 2. Portenoy, Clin J Pain, 2006.)
N Vasisht, J Stark, A Finn; BioDelivery Sciences International, Raleigh, NC Oral transmucosal delivery of fentanyl is a rapid and proven route of administration for the management of breakthrough pain in cancer patients.1,2 The BEMA drug delivery system was designed to improve oral transmucosal dosing reliability, tolerability and patient acceptance. This bilayer polymer delivery system can control the mucosal surface application area and time in contact with the mucosa, optimizing delivery and pharmacokinetics of buccally delivered fentanyl. The linearity of plasma fentanyl concentrations across a range of doses and the absolute bioavailability of fentanyl were explored in two Phase 1 pharmacokinetic studies. Single doses of BEMA fentanyl (200, 600, 1200 g) were administered buccally to 12 healthy volunteers 72 hours apart in an open-label, randomized, single-dose, 3-period, crossover study. In a second randomized, single-dose, 4-period, crossover study, 12 healthy volunteers received single fentanyl doses (200 g intravenously, 800 g orally, single 800 g BEMA fentanyl, and four 200 g BEMA fentanyl) 72 hours apart. All subjects were premedicated with naltrexone and monitored for safety. Serial blood samples were collected over a 48-hour period after each dose and measured for plasma fentanyl. In the dose linearity study, mean Cmax values for the 200, 600, and 1200 g BEMA fentanyl doses were 0.38, 1.16, and 2.19 ng/mL, respectively. The corresponding values for mean AUCinf were 3.46, 11.72, and 20.43 ng*hr/mL, respectively. The absolute bioavailability of fentanyl was ⬎70% for both a single and multi-unit (4x200 g) regimen, of which 51% was absorbed through the buccal mucosa. BEMA fentanyl demonstrates linear dos‘eexposure and multi-unit predictability in mean peak plasma concentrations and systemic exposure of fentanyl. The BEMA system delivers a high percentage of the fentanyl dose through the buccal mucosa, which results in an absolute fentanyl bioavailability of ⬎70%. Research supported by BioDelivery Sciences International. (1. Farrar, JNCI, 1998; 2. Portenoy, Clin J Pain, 2006.)
P23 (190) The safety of BEMA (BioErodible MucoAdhesive) fentanyl use for breakthrough pain (BTP) in cancer patients N Slatkin, W Hill, A Finn; City of Hope, Department of Supportive Care, Pain and Palliative Medicine, Duarte, CA The BEMA drug delivery system was designed to improve oral transmucosal dosing reliability, tolerability, and patient acceptance. The mucoadhesive polymers adhere and deliver fentanyl across the capillary rich mucosa. Two-hundred twenty (220) adult opioid-tolerant patients with chronic cancer pain who experienced one to four daily episodes of BTP while on stable opioid doses (i.e., a daily dose equal in analgesic activity to at least 60 mg of oral morphine) received BEMA fentanyl in an openlabel, multicenter study. Patients were titrated to an effective dose and then continued with dosage adjustment as required. The initial effective dose was ⱕ1200 g in 94.3% of subjects entering the Open-label Period. Administration of the initial 200 g dose of BEMA fentanyl to 97/220 subjects was monitored by study personnel; none of the subjects experienced AEs. Patients received, on average, 2.9 doses per day for 111.9 days (maximum exposure duration of 531 days). The most frequently reported AEs attributed to study drug were nausea (8.6%), dizziness (5.5%), constipation (5.0%), and somnolence (4.5%); these four AEs were also the only AEs that appeared to be dose-related (during the Titration Period only). Although more than 56,000 episodes of BTP were treated with BEMA fentanyl in this study, only one case of respiratory depression was reported, an event not attributed to study drug. There were no deaths attributed to study drug. There was no relationship between the incidence of AEs and age, gender or race. Three (1.4%) subjects experienced mild stomatitis that was possibly related to BEMA fentanyl; none resulted in study drug discontinuation. The AE profile of BEMA fentanyl was consistent with the use of an opioid in patients with cancer and chronic pain. Research supported by BioDelivery Sciences International.
(189) Rapid and effective control of breakthrough pain (BTP) and tolerability in cancer patients treated with BEMA (BioErodible MucoAdhesive) fentanyl
(191) Dose linearity and absolute bioavailability of BEMA (BioErodible MucoAdhesive) fentanyl in healthy volunteers
J North, R Kapoor, J Bull, W Reid, A Finn; Carolinas Pain Institute, WinstonSalem, NC Transmucosal delivery of fentanyl can provide prompt control of BTP in patients taking stable doses of opioids for chronic pain.1,2 The BEMA drug delivery system was designed to improve transmucosal dosing reliability, tolerability, and patient acceptance. BEMA Fentanyl consists of a small unit that is placed against the oral mucosa. The mucoadhesive polymers adhere to the membrane and deliver fentanyl across the capillary rich mucosa. Eighty adult cancer patients on stable opioid doses who achieved adequate control of BTP with BEMA fentanyl (200 to 1200 g) in an open-label titration phase were treated for up to 9 BTP episodes with the previously determined BEMA fentanyl dose (6 episodes) and placebo (3 episodes) in a double-blind random sequence. Subjects recorded pain intensity (PI; 11-point scale) at the time of treatment, and at 5, 10, 15, 30, 45, and 60 minutes after treatment. The primary outcome measure was the sum of PI differences (SPID) at 30 minutes. A total of 394 BTP episodes were treated with BEMA fentanyl and 197 with placebo. Of the patients who entered the study, only 3.3% of patients withdrew for lack of effective pain relief in the titration phase. SPID values for BEMA fentanyl-treated episodes were statistically significantly greater than placebo-treated episodes at 15 minutes (12.7⫾0.88 vs. 10.6⫾1.06; p⫽0.047), 30 minutes (49.1⫾2.40 vs. 39.0⫾2.95, p⫽0.004), and through 60 minutes. The most commonly reported treatment-related adverse events were somnolence (6.0%), nausea (5.3%), dizziness (4.6%), and vomiting (4.0%), which are commonly associated with opioid use. There were no reports of treatment-related mucositis or respiratory depression during the study. BEMA fentanyl provided patients with a rapid, effective, and convenient means to control cancer BTP with a favorable tolerability profile. Research supported by BioDelivery Sciences International (1. Farrar, JNCI,1998; 2. Portenoy, Clin J Pain, 2006.)
N Vasisht, J Stark, A Finn; BioDelivery Sciences International, Raleigh, NC Oral transmucosal delivery of fentanyl is a rapid and proven route of administration for the management of breakthrough pain in cancer patients.1,2 The BEMA drug delivery system was designed to improve oral transmucosal dosing reliability, tolerability and patient acceptance. This bilayer polymer delivery system can control the mucosal surface application area and time in contact with the mucosa, optimizing delivery and pharmacokinetics of buccally delivered fentanyl. The linearity of plasma fentanyl concentrations across a range of doses and the absolute bioavailability of fentanyl were explored in two Phase 1 pharmacokinetic studies. Single doses of BEMA fentanyl (200, 600, 1200 g) were administered buccally to 12 healthy volunteers 72 hours apart in an open-label, randomized, single-dose, 3-period, crossover study. In a second randomized, single-dose, 4-period, crossover study, 12 healthy volunteers received single fentanyl doses (200 g intravenously, 800 g orally, single 800 g BEMA fentanyl, and four 200 g BEMA fentanyl) 72 hours apart. All subjects were premedicated with naltrexone and monitored for safety. Serial blood samples were collected over a 48-hour period after each dose and measured for plasma fentanyl. In the dose linearity study, mean Cmax values for the 200, 600, and 1200 g BEMA fentanyl doses were 0.38, 1.16, and 2.19 ng/mL, respectively. The corresponding values for mean AUCinf were 3.46, 11.72, and 20.43 ng*hr/mL, respectively. The absolute bioavailability of fentanyl was ⬎70% for both a single and multi-unit (4x200 g) regimen, of which 51% was absorbed through the buccal mucosa. BEMA fentanyl demonstrates linear dos‘eexposure and multi-unit predictability in mean peak plasma concentrations and systemic exposure of fentanyl. The BEMA system delivers a high percentage of the fentanyl dose through the buccal mucosa, which results in an absolute fentanyl bioavailability of ⬎70%. Research supported by BioDelivery Sciences International. (1. Farrar, JNCI, 1998; 2. Portenoy, Clin J Pain, 2006.)