scholarly journals Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma

2014 ◽  
Vol 4 (2) ◽  
pp. e182-e182 ◽  
Author(s):  
D S Siegel ◽  
P Richardson ◽  
M Dimopoulos ◽  
P Moreau ◽  
C Mitsiades ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Study Drug ◽  
Maximum Tolerated Dose ◽  
Laboratory Studies ◽  
Open Label ◽  
Adverse Experiences ◽  
Previously Treated ◽  
Dose Escalating

Abstract The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1–7 and 15–21, 25 mg lenalidomide on days 1–21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed.

scholarly journals Phase 1 Study of High-Specific-Activity I-131 MIBG for Metastatic and/or Recurrent Pheochromocytoma or Paraganglioma

2017 ◽  
Vol 103 (1) ◽  
pp. 213-220 ◽  
Author(s):  
Richard B Noto ◽  
Daniel A Pryma ◽  
Jessica Jensen ◽  
Tess Lin ◽  
Nancy Stambler ◽  
...  
Keyword(s):  
Partial Response ◽  
Adverse Events ◽  
Specific Activity ◽  
Phase 1 ◽  
High Specific Activity ◽  
Absorbed Dose ◽  
Study Drug ◽  
The United States ◽  
Maximum Tolerated Dose ◽  
Open Label

Abstract Context No therapies are approved for the treatment of metastatic and/or recurrent pheochromocytoma or paraganglioma (PPGL) in the United States. Objective To determine the maximum tolerated dose (MTD) of high-specific-activity I-131 meta-iodobenzylguanidine (MIBG) for the treatment of metastatic and/or recurrent PPGL. Design Phase 1, dose-escalating study to determine the MTD via a standard 3 + 3 design, escalating by 37 MBq/kg starting at 222 MBq/kg. Setting Three centers. Patients Twenty-one patients were eligible, received study drug, and were evaluable for MTD, response, and toxicity. Intervention Open-label use of high-specific-activity I-131 MIBG therapy. Main Outcome Measures Dose-limiting toxicities, adverse events, radiation absorbed dose estimates, radiographic tumor response, biochemical response, and survival. Results The MTD was determined to be 296 MBq/kg on the basis of two observed dose-limiting toxicities at the next dose level. The highest mean radiation absorbed dose estimates were in the thyroid and lower large intestinal wall (each 1.2 mGy/MBq). Response was evaluated by total administered activity: four patients (19%), all of whom received >18.5 GBq of study drug, had radiographic tumor responses of partial response by Response Evaluation Criteria in Solid Tumors. Best biochemical responses (complete or partial response) for serum chromogranin A and total metanephrines were observed in 80% and 64% of patients, respectively. Overall survival was 85.7% at 1 year and 61.9% at 2 years after treatment. The majority (84%) of adverse events were considered mild or moderate in severity. Conclusions These findings support further development of high-specific-activity I-131 MIBG for the treatment of metastatic and/or recurrent PPGL at an MTD of 296 MBq/kg.

scholarly journals Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study

Blood ◽  
2012 ◽  
Vol 119 (20) ◽  
pp. 4608-4613 ◽  
Author(s):  
Suzanne Lentzsch ◽  
Amy O'Sullivan ◽  
Ryan C. Kennedy ◽  
Mohammad Abbas ◽  
Lijun Dai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Response Rate ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Open Label ◽  
Dose Escalation Study ◽  
Refractory Multiple Myeloma ◽  
One Year

Abstract This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m2 (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704.

Combination of Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) in Relapsed/Refractory Multiple Myeloma: Results of a Multicenter Phase II Clinical Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 868-868 ◽  
Author(s):  
Antonio Palumbo ◽  
Patrizia Falco ◽  
Grazia Sanpaolo ◽  
Antonietta Falcone ◽  
Vincenzo Ferderico ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Drug Combination ◽  
Response Rate ◽  
Oral Prednisone ◽  
Cell Transplant ◽  
Second Line ◽  
Open Label ◽  
Grade 3

Abstract Background: In newly diagnosed multiple myeloma (MM) patients the addition of lenalidomide or thalidomide or bortezomib to the standard oral melphalan and prednisone (MP) combination significantly increased response rate and event-free survival. In advanced MM, the 4 drug combination VMPT further improves response rate. In this multicenter open label phase I/II trial the safety/efficacy profile of the 4 drug combination, lenalidomide, melphalan, prednisone and thalidomide (RMPT) was evaluated in patients with relapsed/refractory myeloma. Methods: Oral lenalidomide was administered at 10 mg/day on days 1–21, oral melphalan at 0.18 mg/kg on days 1–4, oral prednisone at 2 mg/kg on days 1–4. Thalidomide was administered at 50 mg/day (Arm A) or 100 mg/day (Arm B) on days 1–28. Each course was repeated every 28 days for a total of 6 courses. Aspirin 100 mg/day was given as a prophylaxis for thrombosis. Maintenance therapy included lenalidomide alone at 10 mg/day on days 1–21. Results: Forthy-four patients, median age 69 years (range 47–80), with relapsed or refractory MM were enrolled. Twenty-six patients received RMPT as second line of therapy, 18 as third line. Twenty patients received prior autologous transplant, 10 thalidomide-based regimen, 9 bortezomib-based regimen and 3 allogeneic stem cell transplant. After a median of 2 courses, 75.8% of patients achieved at least a partial response (PR), including 30% very good partial response (VGPR). Among patients who received RMPT as second line therapy the PR rate was 81.8%, including VGPR 36.4%.Among patients who received thalidomide 100 mg, the PR rate was 93.3% (including VGPR 46.7%) compared to 64.7% of thalidomide 50 mg. The 1-year-progressionfree survival was 48.6% and the 1-year survival from study entry was 90%. Grade 3–4 hematologic adverse events included: neutropenia (66.6%), thrombocytopenia (36.3%) and anemia (30.2%). Grade 3–4 non hematologic adverse events included: infections (21.2%), neurological toxicity (6%) and fatigue (9%). No thromboembolic events were reported. Conclusion: Initial results showed that RMPT is an effective salvage therapy with a high proportion of responses. Toxicities were manageable. No thromboembolic complications were reported.

Melphalan, Prednisone, and Lenalidomide Treatment for Newly Diagnosed Myeloma: A Report From the GIMEMA—Italian Multiple Myeloma Network

2007 ◽  
Vol 25 (28) ◽  
pp. 4459-4465 ◽  
Author(s):  
Antonio Palumbo ◽  
Patrizia Falco ◽  
Paolo Corradini ◽  
Antonietta Falcone ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Survival Rates ◽  
Standard Of Care ◽  
Maximum Tolerated Dose ◽  
Treatment Schedule ◽  
Newly Diagnosed ◽  
Low Incidence ◽  
Grade 3

PurposeLenalidomide has shown significant antimyeloma activity in clinical studies. Oral melphalan, prednisone, and thalidomide have been regarded as the standard of care in elderly multiple myeloma patients. We assessed dosing, efficacy, and safety of melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed elderly myeloma patients.Patients and MethodsOral melphalan was administered in doses ranging from 0.18 to 0.25 mg/kg on days 1 to 4, prednisone at a 2-mg/kg dose on days 1 to 4, and lenalidomide at doses ranging from 5 to 10 mg on days 1 to 21, every 28 days for nine cycles, followed by maintenance therapy with lenalidomide alone. Aspirin was given as a prophylaxis for thrombosis.ResultsFifty-four patients were enrolled and evaluated after completing the assigned treatment schedule. The maximum tolerated dose was defined as 0.18 mg/kg melphalan and 10 mg lenalidomide. With these doses, 81% of patients achieved at least a partial response, 47.6% achieved a very good partial response, and 23.8% achieved a complete immunofixation-negative response. In all patients, 1-year event-free and overall survival rates were 92% and 100%, respectively. At the maximum tolerated dose, grade 3 adverse events included neutropenia (38.1%), thrombocytopenia (14.2%), febrile neutropenia (9.5%), vasculitis (9.5%), and thromboembolism (4.8%); grade 4 adverse events were neutropenia (14.2%) and thrombocytopenia (9.5%).ConclusionOral MPR therapy is a promising first-line treatment for elderly myeloma patients. Hematologic adverse events were frequent but manageable. A low incidence of nonhematologic adverse events was noted. Aspirin appears to provide adequate antithrombosis prophylaxis.

scholarly journals A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma

Blood ◽  
2012 ◽  
Vol 120 (3) ◽  
pp. 552-559 ◽  
Author(s):  
Jeffrey A. Zonder ◽  
Ann F. Mohrbacher ◽  
Seema Singhal ◽  
Frits van Rhee ◽  
William I. Bensinger ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Stable Disease ◽  
Plasma Cells ◽  
Phase 1 ◽  
Human Study ◽  
Maximum Tolerated Dose ◽  
Open Label ◽  
Dose Escalation Study ◽  
Label Dose

Abstract This multicenter, first-in-human study evaluated the safety, tolerability, and pharmacokinetic and pharmacodynamic properties of the anti-CS1 monoclonal antibody elotuzumab. A standard 3 + 3 design was used to determine maximum tolerated dose; dose-limiting toxicities were assessed during cycle 1. Thirty-five patients with relapsed/refractory multiple myeloma were treated with intravenous elotuzumab at doses ranging from 0.5 to 20 mg/kg every 2 weeks. Patients who achieved at least stable disease after 4 treatments could receive another 4 treatments. No maximum tolerated dose was identified up to the maximum planned dose of 20 mg/kg. The most common adverse events, regardless of attribution, were cough, headache, back pain, fever, and chills. Adverse events were generally mild to moderate in severity, and adverse events attributed to study medication were primarily infusion-related. Plasma elotuzumab levels and terminal half-life increased with dose whereas clearance decreased, suggesting target-mediated clearance. CS1 on bone marrow–derived plasma cells was reliably saturated (≥ 95%) at the 10-mg/kg and 20-mg/kg dose levels. Using the European Group for Bone and Marrow Transplantation myeloma response criteria, 9 patients (26.5%) had stable disease. In summary, elotuzumab was generally well tolerated in this population, justifying further exploration of this agent in combination regimens.

Anlotinib plus TQB2450 in patients with advanced refractory biliary tract cancer (BTC): An open-label, dose-escalating, and dose-expansion cohort of phase Ib trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 292-292
Author(s):  
Jun Zhou ◽  
Jifang Gong ◽  
Yanshuo Cao ◽  
Zhi Peng ◽  
Jiajia Yuan ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Safety Profile ◽  
Kinase Inhibitor ◽  
Maximum Tolerated Dose ◽  
Study Cohort ◽  
Open Label ◽  
Extrahepatic Cholangiocarcinoma ◽  
Cell Counts ◽  
Previously Treated ◽  
Dose Escalating

292 Background: Anti-angiogenic agents have been clinically investigated in combination with anti-PD-1/L1 mAbs due to their immuno-modulatory effects. Anlotinib (A), a potent oral multi-target tyrosine kinase inhibitor, has anti-angiogenic properties and anti-tumor efficacy with a favorable toxicity profile. The combination of A and TQB2450 (T), an anti-PD-L1 mAb, exhibited superior tumor growth suppression compared to either monotherapy in murine models. This ongoing phase 1b study cohort is aimed to assess the safety and efficacy of A+T in pts with advanced BTC. Methods: In this study cohort, patients (pts) with previously treated, advanced BTC were enrolled. A 3+3 dose escalation was used to determine the maximum tolerated dose (MTD) and a recommended phase 2 dose (RP2D) in a dose-escalating stage. Additional pts were enrolled in a dose-expansion stage to further establish the safety and determine the preliminary efficacy. Oral A of 10 and 12 mg was administered once daily for 14 days on / 7 days off with intravenous T of 1200 mg every 3 weeks. The primary endpoint was dose-limiting toxicity (DLT) during first cycle (first 3 weeks) to estimate the MTD, RP2D and overall response rate (ORR). Tumor response was assessed according to RECIST version 1.1 and iRECIST. The Secondary endpoints were progression-free survival (PFS), disease control rate (DCR) and safety. Results:25 pts were enrolled (8 with intrahepatic cholangiocarcinoma [IHCC]; 8 with extrahepatic cholangiocarcinoma [EHCC]; 9 with gall bladder cancer [GBC]) until August 2020. Median number of prior lines of therapy was 1 (range 1-5). During dose-escalation, no DLT was observed and 12 mg anlotinib was determined as RP2D for expansion. Among 24 evaluable pts (with at least once tumor assessment), 3 had achieved complete response (CR) and 7 had partial response (PR), which were all treated by 12 mg anlotinib plus TQB2450, 8 had stable disease (SD) and 6 had progression disease (PD). ORR was 41.67% and DCR was 75%. 10 pts were still on treatment. The median PFS was 240 days (95% CI, 83~NR).Treatment-related adverse events (TRAEs) occurred in 83.3% of pts (G3/4 in 16.7% [4/24], and leading to treatment discontinuation in 4.2% [1/24]). The most common TRAEs were hypertension (33.3%), decreased white blood cell counts (25.0%), increased TBIL (20.8%), decreased neutrophil counts (20.8%), increased DBIL (12.5%), and increased IBIL (12.5%). Conclusions: A+T had a manageable safety profile and encouraging antitumor efficacy in pts with previously treated, advanced BTC. No unexpected AEs were identified beyond the established safety profile for each agent. Clinical trial information: NCT03996408.

A phase I study of an IDO inhibitor (SHR9146) plus camrelizumab and in combination with/without apatinib in patients with advanced solid tumors: Safety and efficacy analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3101-3101
Author(s):  
Ying Cheng ◽  
Ying Liu ◽  
Jinhua Xu ◽  
Jing Zhu ◽  
Ying Wang ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase I ◽  
Solid Tumors ◽  
Renal Cancer ◽  
Phase I Study ◽  
Angiogenesis Inhibitor ◽  
Maximum Tolerated Dose ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Safety And Efficacy

3101 Background: IDO is an enzyme of interest in immuno-oncology because of the immunosuppressive effects that result from its role in tryptophan catabolism. Clinical trials of IDO inhibitors with immunotherapy are under active investigation. The addition of angiogenesis inhibitor may further enhance the anti-tumor immune responses. Here we report the safety and efficacy results of SHR9146 (IDO inhibitor) plus camrelizumab (PD-1 antibody) with/without apatinib (VEGFR-2 inhibitor) in patients (pts) with advanced solid cancers who failed standard antitumor therapies. Methods: This was an open-label, phase I study. Eligible puts would receive SHR9146 (escalated dose) plus camrelizumab (200 mg IV, q2w) alone (Cohort A) or in combination with apatinib (250 mg p.o. qd) (Cohort B). Each cohort was conducted according to a 3+3 dose escalation design. The starting dose of SHR9146 was 100mg bid, followed by 200, 400, 600 mg bid. The two primary endpoints were Dose-limiting Toxicity (DLT) and Maximum Tolerated Dose (MDT). The secondary objective was to analysis the incidence of Adverse Events (AEs) and efficacy. Results: As of Oct 31, 2020, 23 pts have been enrolled (Cohort A:14, Cohort B: 9; median age: 54 years; median prior therapies: 2 lines;). Cohort A was escalating at 600mg, and Cohort B was escalating at 400mg. Two pts experienced DLTs: one DLT (G4 hypercalcemia) was observed at 600mg in Cohort A; the other DLT (G3 rash) was observed at 400mg in Cohort B. MDT was not reached and the study was still ongoing. In Cohort A, ORR and DCR in evaluable pts were 21.4% (3/14, all confirmed) and 42.9% (6/14). Partial response was observed in 3 pts with liver cancer (1/3), renal cancer (1/3), and cervix cancer (1/3). In Cohort B, ORR and DCR in evaluable pts were 33.3%(3/9, all confirmed) and 77.8%(7/9). Partial response was observed in 3 pts with SCLC (1/3), prostate cancer (1/3) and renal cancer (1/3). The incidence of pts with TRAEs and grade>=3 TRAEs were 91.3% (21/23) and 39.1% (9/23) respectively. The most common grade>=3 TRAEs were hypercalcemia (26.1%, 6/23), fatigue (17.4%, 4/23) and nausea (13.0%, 3/23). No fatal AEs were observed. G3 nausea, G3 lipase increased and G2 GGT increased resulted in SHR9146 dose reduction in 3 pts (Cohort A). Conclusions: SHR9146 plus camrelizumab in combination with/without apatinib demonstrated promising anti-tumor activity with acceptable safety in pts with advanced solid tumors. Further study is needed to validate the efficacy and safety. Clinical trial information: NCT03491631.

scholarly journals Carfilzomib Thalidomide and Dexamethasone Is Safe and Effective in the Treatment of Relapsed/Refractory Multiple Myeloma: An Open Label Phase II Australasian Leukaemia and Lymphoma Group (ALLG) MM 018/ Asian Myeloma Network (AMN) 002 Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Hang Quach ◽  
Simon J Harrison ◽  
Je-Jung Lee ◽  
Nichloas Murphy ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Board Of Directors ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Research Funding ◽  
Open Label ◽  
Advisory Committees ◽  
Open Label Phase ◽  
Grade 3

Background: The combination of carfilzomib with immunomodulatory drugs (IMiDs) and dexamethasone is active in multiple myeloma (MM). Carfilzomib, thalidomide, and dexamethasone (KTd) has been studied in upfront MM treatment but has not been studied in the setting of relapsed/refractory myeloma (RRMM). The ALLG MM018/ AMN002 is an open-label phase II study of KTd in patients with RRMM. This study was conducted across 16 sites across Australia, New-Zealand, Singapore, South Korea and Taiwan. Method: Patients with RRMM with 1-3 prior lines of treatment were given carfilzomib [K: 20mg/m2 IV cycle 1 days 1 and 2, 56mg/m2 (36mg/m2 for patients age ≥75 years) from cycle 1 day 8 onwards], thalidomide (T: 100mg po nocte) and dexamethasone [dex: 40mg (20mg for patients age ≥75 years) po weekly], in a 28-day cycle. After 12 cycles, T was omitted, and K was given on days 1,2,15,16 and dex days 1,15 every 28-day cycles for a further six cycles. The primary endpoint was PFS. Secondary endpoints were ORR, overall survival, adverse events, and quality of life (QoL). The study had an 80% power to detect a ≥70% PFS at 6.5 months compared to historical ≤50% PFS at 6.5 months expected with Td (Kropff, M. et al. Haematologica 2012), at a significance level of 0.05. Results: This study has completed accrual. Eighty-three patients [median age of 66 years (42-85)] were enrolled with a median follow up of 15.9 (0.9-26) months. ORR rates were 86.4% (≥VGPR 70.2%). Median PFS was 20m (95% CI 15.9-26m). PFS at 6.5 months was 76.2% (95% CI 73.6-84.9%). Median OS has not been reached, and was 75% at 20 months. The most common grade ≥3/4 AEs were peripheral neuropathy (16%), upper respiratory tract infections (12%), dyspnoea (14%), and hypertension (10%). Grade ≥3/4 cardiac AEs occurred in 6%. The median carfilzomib dose that was delivered was 70.7% (32.8-92.6%) of the target dose. Thus far, 41% of patients have completed the intended 18 cycles of treatment. 21% of patients ceased therapy early. The most common reason for early treatment cessation was disease progression (30%) and adverse events (15%). Fifteen patients (18%) have died, 11 were due to MM, two from infection, one from an ischaemic cardiac event, and one from a traffic accident. QoL, as measured by the EQ-5D-5L instrument, remained stable throughout treatment. Conclusion: The ALLG MM018/AMN 002 study has met its primary endpoint. The KTd schedule as outlined in this study is efficacious in patients with RRMM, resulting in a prolonged PFS and a safety profile in line with previous reports for each of carfilzomib and thalidomide. KTd is an active option in jurisdictions where the cost of other IMiDs prohibits regulatory funding. Comparisons of efficacy and adverse events between the Caucasian and Asian populations will be presented at the meeting. Disclosures Quach: Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Sanofi: Consultancy, Research Funding. Harrison:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; CRISPR Therapeutics: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: wrt panobinostat; Haemalogix: Consultancy. Augustson:Roche: Other: Support of parent study and funding of editorial support. Campbell:Amgen, Novartis, Roche, Janssen, Celgene (BMS): Research Funding; AstraZeneca, Janssen, Roche, Amgen, CSL Behring, Novartis: Consultancy. Soo:Hanmi: Research Funding. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.

scholarly journals Effect of Tipranavir-Ritonavir on Pharmacokinetics of Raltegravir

2009 ◽  
Vol 53 (7) ◽  
pp. 2752-2755 ◽  
Author(s):  
William D. Hanley ◽  
Larissa A. Wenning ◽  
Allison Moreau ◽  
James T. Kost ◽  
Eric Mangin ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Study Drug ◽  
Integrase Inhibitor ◽  
Phase Iii ◽  
Open Label ◽  
Time Curve ◽  
Period 2 ◽  
Adverse Experiences ◽  
Immunodeficiency Virus

ABSTRACT Raltegravir (RAL) is a novel and potent human immunodeficiency virus type 1 integrase inhibitor that is predominantly metabolized via glucuronidation. The protease inhibitor combination tipranavir (TPV) at 500 mg and ritonavir (RTV) at 200 mg (TPV-RTV) has inhibitory and inductive effects on metabolic enzymes, which includes the potential to induce glucuronosyltransferase. Because RAL may be coadministered with TPV-RTV, there is the potential for the induction of RAL metabolism. Consequently, we assessed the effect of TPV-RTV on the pharmacokinetics of RAL and the safety and tolerability of this combination. Eighteen healthy adults were enrolled in this open-label study. The participants received RAL at 400 mg twice daily for 4 days (period 1) and TPV-RTV twice daily for 7 days (period 2), followed immediately by 400 mg RAL with TPV-RTV twice daily for 4 days (period 3). Under steady-state conditions, the RAL concentration at 12 h (C 12) was decreased when RAL was administered with TPV-RTV (geometric mean ratio [GMR], 0.45; 90% confidence interval [CI] 0.31, 0.66; P = 0.0021); however, the area under the concentration-time curve from time zero to 12 h (GMR, 0.76; 90% CI, 0.49, 1.19; P = 0.2997) and the maximum concentration in serum (GMR, 0.82; 90% CI, 0.46, 1.46; P = 0.5506) were not substantially affected. There were no serious adverse experiences or discontinuations due to study drug-related adverse experiences, and RAL coadministered with TPV-RTV was generally well tolerated. Although the RAL C 12 was decreased with TPV-RTV in this study, favorable efficacy data collected in phase III studies substantiate that TPV-RTV may be coadministered with RAL without dose adjustment.

Effectiveness and Safety of Rizatriptan Benzoate 10 mg in the Treatment of Migraine Headaches

2010 ◽  
Vol 2 ◽  
pp. CMT.S4670
Author(s):  
Michel Aubé ◽  
Fridon Chouha ◽  
Julie Vaillancourt ◽  
John Sampalis
Keyword(s):  
Adverse Events ◽  
Real Life ◽  
Study Drug ◽  
Pain Severity ◽  
Open Label ◽  
Serious Adverse Events ◽  
Over The Counter ◽  
Rizatriptan Benzoate ◽  
Migraine Headaches ◽  
Real Life Setting

Background Patients that do not achieve therapeutic response with over the counter non-triptan medications may benefit from triptan-based treatments. Objective Phase I V, open-label, multi-center, prospective cohort study assessing the effectiveness of rizatriptan in the management of migraines for patients that have not responded to non-triptan treatment. Methods Patients were treated with one rizatriptan (MAXALT RPD®) 10 mg wafer at the onset of each migraine attack and were assessed after a minimum of one and a maximum of two consecutive headache episodes. Outcome measures included self-reported assessments (severity and duration of migraine headache) and the Migraine ACT questionnaire. Results A total of 369 patients were enrolled, of which 291 and 215 reported one and two attacks, respectively. For the first and second attacks, 47.2% and 53.9% of patients reported complete resolution of pain while 73.6% and 77.0% reported pain severity reduction within two hours of onset. Mean (SD) pain severity score (four-point Likert scale) during the 488 migraine episodes was reduced significantly ( P < 0.001) from 2.56 (0.49) at onset to 1.91 (0.85) at 30, 1.31 (1.00) at 60 and 0.84 (1.00) at 120 minutes. Similar improvements were observed for changes in Migraine ACT questionnaire scores. No treatment-related serious adverse events were reported. The most frequently reported non-serious adverse events that were attributed to the study drug were dizziness (2.2%), chest discomfort (1.1%), nausea (1.1%), and somnolence (0.8%). Conclusion In a real-life setting, rizatriptan benzoate 10 mg is effective and safe in the treatment of acute migraine headaches in patients who do not respond to non-triptan treatment.

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