Long-term tolerability of fentanyl effervescent buccal tablets: Interim analysis in patients with cancer-related breakthrough pain

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8567-8567
Author(s):  
N. Slatkin ◽  
V. Charu ◽  
G. Niebler ◽  
R. Rauck
Keyword(s):  
Interim Analysis ◽  
Breakthrough Pain ◽  
Safety Data ◽  
Dose Titration ◽  
Open Label ◽  
Patients With Cancer ◽  
Titration Phase ◽  
Term Tolerability ◽  
Buccal Tablets

8567 Background: Fentanyl effervescent buccal tablets (FEBT) are designed to enhance the rate and efficiency of fentanyl absorption through the buccal mucosa. Results reported here represent a pre-specified interim analysis of an open-label safety and efficacy study of FEBT in opioid-tolerant patients with cancer-related breakthrough pain (BTP). Methods: Patients with cancer-related BTP receiving around-the-clock and supplemental opioids were eligible to enroll. Patients who had participated in a previous dose-titration study of FEBT enrolled directly into the 1-year phase; new patients entered a titration phase to determine an effective FEBT dose before entering the 1-year phase. An effective FEBT dose was defined as the dose needed to provide adequate analgesia for BTP. By October 3, 2005, 170 patients (aged 24 to 95 years) received FEBT (100–800 μg) and had documented safety data. Results: Of the 112 new patients, 70.5% identified an effective FEBT dose and were eligible for enrollment. In the long-term phase, patients received FEBT for a mean of 109.8 days; 8% at 100 μg, 15% at 200 μg, 23% at 400 μg, 25% at 600 μg, and 29% at 800 μg. The FEBT dose remained reasonably stable during the long-term phase, but 43 patients had a dose increase and 6 had a dose decrease at the discretion of the investigator. Only 2 patients required a change in the FEBT dose because of tolerability. The most common adverse events (AEs) are given in the table. The incidence of AEs did not correlate with the effective FEBT dose. The 42 patient deaths that occurred were all attributed to cancer-related pathology or the progression of cancer. Conclusions: Overall, FEBT was well tolerated in opioid-tolerant patients with cancer-related BTP. [Table: see text] [Table: see text]

scholarly journals P219 Long-term safety of filgotinib in patients with PsA: week 52 safety data from a Phase 2 open-label extension study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Laura Coates ◽  
Philip Mease ◽  
Dafna Gladman ◽  
Filip Van den Bosch ◽  
Anna Rychlewska-Hanczewska ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Safety Data ◽  
Janus Kinase ◽  
Controlled Study ◽  
Stock Ownership ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

Abstract Background Filgotinib (FIL) is an orally administered, selective janus kinase 1 (JAK1) inhibitor in development for psoriatic arthritis (PsA). Efficacy and safety of FIL in patients with active PsA were evaluated in a 16-week phase 2 study (EQUATOR, NCT03101670). After 16 weeks, patients could roll-over to an Open Label Extension (OLE) Study (EQUATOR2, NCT03320876) for the purpose of evaluating long-term safety and efficacy. The aim of this analysis was to assess safety and efficacy through 52 weeks of exposure to filgotinib. Methods Patients who completed the randomised, double-blind, placebo-controlled study were eligible for participation in the OLE, during which all patients received once daily (qd) open-label FIL 200mg. In this interim analysis of OLE, for the safety analysis, all data were included from the screening in the core study up to the data cut of 18 April 2019 in the OLE. For the efficacy analysis, all data until OLE Week 52 visit for each patient were included (observed case analysis). Results Of the 131 patients randomised and dosed in EQUATOR, 124 (95%) completed the study and 122 (93%) enrolled in EQUATOR2; 50% were female and mean age was 50. At this interim analysis, 106/122 (87%) remained in the OLE (premature discontinuations during OLE due to: 4 for safety, 11 withdrew consent, and 1 for other reasons). Cumulative patient years of exposure (PYE) on FIL were 160, median time on FIL was 66 weeks. Key safety data are summarised in Table 1. Key ≥Grade 2 treatment-emergent laboratory abnormalities seen with FIL arm (N = 128) compared with PBO (N = 66) were lymphocyte decrease 11.1% vs 4.5%, neutrophil decrease 5.5% vs 0%, ALT increase 1.6% vs 1.5% and creatinine increase 0.8% vs 0%, respectively. At week 52, 34% of the patients fulfilled criteria for minimal disease activity and 81%, 55%, and 33% of patients, respectively, achieved ACR20/50/70 responses. Conclusion FIL 200mg qd was generally well tolerated and the safety profile in PsA was comparable to that observed in the FIL rheumatoid arthritis studies. The data from this interim analysis suggest that further improvement of the patient condition can be expected beyond 16 weeks of treatment. Disclosures L. Coates: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Lilly, Novartis, Pfizer, Prothena, Sun pharma, and UCB. P. Mease: Other; Received support from Abbvie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN, and UCB. D. Gladman: Other; Received support from Abbvie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB, BMS, and Galapagos. F. Van den Bosch: Other; Received support from Abbvie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, and UCB. A. Rychlewska-Hanczewska: Other; Received support from Galapagos and Gilead Sciences. C. Tasset: Corporate appointments; Employee of Galapagos NV. L. Meuleners: Corporate appointments; Employee of Galapagos NV. M. Trivedi: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc... Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. R. Besuyen: Other; Employee of Galapagos NV. P. Helliwell: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Novartis, Pfizer, and UCB.

Long-term use of fentanyl pectin nasal spray in patients with breakthrough pain in cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9563-9563
Author(s):  
Donald Taylor ◽  
Lukas Radbruch ◽  
Julia Revnic ◽  
Luis M. Torres ◽  
John E Ellershaw ◽  
...  
Keyword(s):  
Nasal Spray ◽  
Breakthrough Pain ◽  
Controlled Trial ◽  
Oral Morphine ◽  
Opioid Therapy ◽  
Term Treatment ◽  
Open Label ◽  
Patients With Cancer ◽  
Long Term Treatment

9563 Background: Given that patients with cancer are living longer, there is a need to ensure that treatments used for palliative care are well tolerated and effective during long-term use. The objective of this study was to investigate the use of fentanyl pectin nasal spray (FPNS) for the treatment of breakthrough pain in cancer (BTPc) in patients taking regular opioid therapy. Methods: A total of 401 adult patients, taking at least 60 mg/day oral morphine or equivalent, with an average of 1 to 4 episodes of BTPc per day, who were either newly enrolled or had completed a randomized controlled trial with FPNS, entered into an open-label assessment study (NCT00458510). Of these, 171 patients, continued into an extension period. Up to 4 episodes of BTPc per day were treated with FPNS at titrated doses between 100 µg and 800 µg. Patients returned to the clinic at 4-week intervals for assessment and reporting of any adverse events (AEs). Results: There were 163 patients with documented FPNS use. The mean duration of use was 325 days; 46 patients used FPNS for more than 1 year, while the maximum duration was 3 years and 8 months. In total, 2% of patients withdrew from the study due to lack of efficacy. Seventy-four percent of patients did not change their FPNS dose. The most common AEs, aside from disease progression, were: insomnia, 9.9%; nausea, 9.4%; vomiting, 9.4%; and peripheral edema, 9.4%. The overall incidence of treatment-related AEs was 11.1%, the most common being constipation (4.1%), with no apparent dose relationship. Ten patients (5.8%) experienced treatment-related nasal AEs, which, with the exception of 1 severe event, were all mild or moderate. Conclusions: FPNS appeared to provide a sustained benefit and was well tolerated during the long-term treatment of BTPc. Clinical trial information: NCT00458510.

Finding an appropriate dose of fentanyl effervescent buccal tablets for relief of cancer-related breakthrough pain

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8564-8564
Author(s):  
J. K. Weick ◽  
L. Tremmel ◽  
J. Messina ◽  
R. K. Portenoy
Keyword(s):  
Statistical Power ◽  
Breakthrough Pain ◽  
Transdermal Fentanyl ◽  
Open Label ◽  
Double Blind ◽  
Opioid Dose ◽  
Patients With Cancer ◽  
Supplemental Dose ◽  
Dosing Strategy ◽  
Buccal Tablets

8564 Background: The recommended dose of a short-acting oral opioid used to treat cancer-related breakthrough pain (BTP) is 5%-15% of the equianalgesic around-the-clock (ATC) opioid dose used to control persistent pain; however, this dosing strategy may not be successful when oral transmucosal fentanyl citrate is used. The applicability of this strategy to fentanyl effervescent buccal tablets (FEBT) use was assessed as part of a multicenter study in opioid-treated patients with cancer BTP. Methods: This double-blind, randomized, placebo-controlled, crossover study required 63 evaluable patients for adequate statistical power. Eligible adults were to receive ≥60 mg/day morphine or equivalent for chronic cancer pain and to have experienced 1–4 BTP episodes daily. After open-label titration to an effective FEBT dose, patients were randomized to 1 of 18 predefined sequences of 10 tablets (7 FEBT, 3 placebo). Pain was assessed repeatedly after each dose; the primary efficacy variable was the sum of pain intensity differences at 30 minutes postdose (SPID30). Results: Of 123 enrolled patients, 77 found an effective FEBT dose (100–800 μg) and continued in the double-blind period; 72 were evaluable for efficacy. The SPID30 was 3.0±0.12 (mean±SE) for FEBT vs 1.8±0.18 for placebo (P<.0001). Ratios of the effective FEBT dose to ATC opioid or prior supplemental opioid dose showed no consistent trend (table). An effective FEBT dose showed no meaningful correlation with prior supplemental dose (r2=.094; Pearson’s coefficient=.3066), with ATC dose in patients using oral opioids (r2=.0609; Pearson’s coefficient=.2468), or with ATC dose in patients using transdermal fentanyl or combinations (r2=.1842; Pearson’s coefficient=.4292). Conclusions: There was no relationship between the effective FEBT dose and either ATC opioids or prior supplemental drugs. Therefore, titration, rather than use of a percentage of the ATC dose, is likely to be important in establishing an effective FEBT dose for each patient. [Table: see text] [Table: see text]

Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended-Release in Adolescents With ADHD

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S15) ◽  
pp. 22-30 ◽  
Author(s):  
Timothy E. Wilens ◽  
Thomas J. Spencer ◽  
Joseph Biederman
Keyword(s):  
Extended Release ◽  
Cardiovascular Effects ◽  
Dose Titration ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Open Label Extension ◽  
Short And Long Term ◽  
Clinically Significant

AbstractObjectiveAssess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).MethodsBlood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR(10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study.FindingsChanges in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and pulse (4.4 bpm; P<.0001) were statistically, but not clinically, significant diastolic BP was not significantly changed (0.6 mm Hg) A decrease in QTcB interval (-4.6±19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events.ConclusionCardiovascular effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.

scholarly journals DOP59 Maintenance of remission with tofacitinib in patients with ulcerative colitis: Updated results of a subpopulation analysis from an open-label, long-term extension study, OCTAVE Open

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S098-S099
Author(s):  
J F Colombel ◽  
M T Osterman ◽  
P Ibanez ◽  
A J Thorpe ◽  
H Zhang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Opportunistic Infections ◽  
Safety Data ◽  
Similar Efficacy ◽  
Major Adverse Cardiovascular Events ◽  
Open Label ◽  
Phase 3 ◽  
Vein Thrombosis ◽  
Mayo Score

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety were demonstrated in 3 Phase 3, randomised, placebo-controlled studies in patients with moderate to severe UC.1 An ongoing, Phase 3, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) included patients from OCTAVE Induction 1 and 2 and OCTAVE Sustain. Methods We present data (as of May 2019) from the ‘maintenance remission’ subpopulation in the OLE study who were in remission (total Mayo score ≤2, no individual subscore &gt;1, rectal bleeding subscore of 0) at Week 52 of OCTAVE Sustain (having received tofacitinib 5 or 10 mg twice daily [BID]). These patients received tofacitinib 5 mg BID as per protocol in the OLE study. Efficacy data up to Month 36 of the OLE study (as observed and with non-responder and last observation carried forward imputation [NRI-LOCF]) are presented for this subpopulation. Safety data are reported for all patients who received tofacitinib 5 mg BID in the OLE study. Results Of 944 patients receiving ≥1 dose of tofacitinib in the OLE study, 163 were in remission at Week 52 of OCTAVE Sustain (mean age 45 years; 46.0% female). Of these, 66 (40.5%) and 76 (46.6%) received tofacitinib 5 and 10 mg BID, respectively, in OCTAVE Sustain, and 21 (12.9%) received a placebo. In total, 67/163 (41.1%) patients discontinued the OLE study, 16 (9.8%) due to adverse events (AEs) excl. worsening UC and 15 (9.2%) due to insufficient clinical response. Among patients that continued, efficacy (Table) was maintained over 36 months and was similar irrespective of the dose received in OCTAVE Sustain. Of 175 patients who received tofacitinib 5 mg BID (incl. 163 from the maintenance remission subpopulation), 152 (86.9%), 33 (18.9%) and 20 (11.4%) had AEs, serious AEs and severe AEs, respectively. The most frequent treatment-emergent AEs (TEAEs) were worsening UC (41 patients, 23.4%) and nasopharyngitis (38 patients, 21.7%). Six (3.4%) patients receiving tofacitinib 5 mg BID had serious infections, 11 (6.3%) had herpes zoster (non-serious and serious), 4 (2.3%) had opportunistic infections, 2 (1.1%) had major adverse cardiovascular events and 5 (2.9%) had malignancy (excl. non-melanoma skin cancer). No deep vein thrombosis, pulmonary embolism or deaths were reported in patients receiving tofacitinib 5 mg BID. Conclusion Most patients in remission at Week 52 of OCTAVE Sustain maintained efficacy with tofacitinib 5 mg BID over 36 months in the OLE study. Similar efficacy was observed for patients whose dose was reduced from tofacitinib 10 mg BID in OCTAVE Sustain to 5 mg BID in the OLE study, vs. those who received 5 mg BID throughout both OCTAVE Sustain and the OLE study. No new safety risks were identified. Reference

scholarly journals DOP73 Efficacy and safety of escalation to tofacitinib 10 mg BID for patients with UC following loss of response on 5 mg BID maintenance therapy: Results from OCTAVE open-label, long-term extension study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S110-S111 ◽  
Author(s):  
B E Sands ◽  
A C Moss ◽  
A Armuzzi ◽  
J K Marshall ◽  
J O Lindsay ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Treatment Failure ◽  
Induction Therapy ◽  
Dose Escalation ◽  
Safety Data ◽  
Mucosal Healing ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Open Label

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib have been demonstrated in patients with moderate to severe UC in three Phase 3 studies (OCTAVE Induction 1 and 2 [NCT01465763; NCT01458951]; OCTAVE Sustain [NCT01458574]) [1]. Here, we present updated efficacy and safety data of tofacitinib dose escalation in patients with UC participating in an ongoing, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) [2]. Methods We present updated data from the dose-escalation subpopulation of the OLE study (as of May 2019; database not locked) comprising patients who achieved clinical response (CR) following 8 weeks of tofacitinib 10 mg twice daily (BID) induction therapy, entered OCTAVE Sustain receiving tofacitinib 5 mg BID, experienced treatment failure between Week 8 and Week 52, and subsequently entered OCTAVE Open with escalation to tofacitinib 10 mg BID. Treatment failure was defined as an increase of ≥3 points from maintenance study baseline total Mayo score, plus an increase of ≥1 point in both rectal bleeding subscore and centrally read endoscopic subscore (ES), and an absolute ES of ≥2 after ≥8 weeks of maintenance therapy. CR, mucosal healing (MH) and remission (R) were evaluated at Months 2, 12, 24 and 36 of OCTAVE Open (non-responder imputation and last observation carried forward [NRI-LOCF] and observed data). Safety was evaluated throughout the study. Results Of 944 patients enrolled in the OLE study, the dose escalation subpopulation comprised 59 patients. In these patients, CR, MH and R rates 36 months after dose escalation were, respectively, 40.7%, 39.0% and 30.5% for NRI-LOCF and 95.2%, 86.4% and 66.7% for observed data (Table). Of these 59 patients, 29 had prior tumour necrosis factor inhibitor (TNFi) failure; in these patients, CR, MH and R rates at Month 36 were, respectively, 51.7%, 51.7% and 41.4% for NRI-LOCF, and 100.0%, 92,3% and 75.0% for observed data. Incidence rates for safety events and pt-years’ exposure are reported in the table. Conclusion For most patients who lost initial CR to tofacitinib 10 mg BID induction therapy while on tofacitinib 5 mg BID maintenance therapy, including those with prior TNFi failure, dose-escalation back to 10 mg BID recaptured CR by Month 2 and was generally maintained over 3 years. The safety profile with tofacitinib 10 mg BID in the dose-escalation subpopulation was generally consistent with that in the overall study population, although there was a numerically higher rate of herpes zoster. These analyses are limited by low pt numbers and the absence of a comparator arm. References

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