A Phase II Study Of Aprepitant As Anti-Emetic Prophylaxis In Patients Receiving Induction Chemotherapy For AML

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5035-5035
Author(s):  
Joseph Brandwein ◽  
Karen W.L. WL Yee ◽  
Andre C Schuh ◽  
Vikas Gupta ◽  
Jack T Seki
Keyword(s):  
Induction Chemotherapy ◽  
Phase Ii ◽  
Cumulative Incidence ◽  
Retrospective Cohort ◽  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Open Label Study ◽  
Secondary Endpoints ◽  
Additional Therapy

Abstract Background Standard AML induction chemotherapy includes an anthracycline plus cytarabine (3+7); the former is considered moderately emetogenic. Such patients typically received anti-emetic prophylaxis using a 5-HT3 antagonist; however, many patients continue to experience chemotherapy-induced nausea and vomiting (CINV) requiring additional therapy. Aprepitant is a neurokinin inhibitor with documented efficacy against CINV, but has not been evaluated to date in the setting of AML induction therapy. Patients and Methods Patients with previously untreated AML, receiving induction chemotherapy with daunorubicin 60 mg/m2 IV daily on Days 1-3 plus cytarabine 200 mg/m2 IV daily (100 mg/m2 for patients age 60 and over) as a continuous IV infusion x 7 days, were enrolled in a Phase II single arm open label study. All patients received 5-HT3 antagonist prophylaxis using either granisetron 1 mg IV daily or ondansetron 8 mg IV q12h on the 3 daunorubicin dosing days. In addition, patients received aprepitant 125 mg PO on Day 1 followed by 80 mg PO daily on Days 2-5. No corticosteroids were used. Additional anti-emetic therapy was given as needed, at the discretion of the medical staff, for any nausea or vomiting. The primary endpoint was any vomiting or retching, while secondary endpoints included nausea requiring supplemental anti-emetics. Results were compared to a retrospective cohort of 40 patients who had received the same AML induction chemotherapy and 5-HT3 antagonist prophylaxis, but without aprepitant. Results At a pre-planned interim analysis, 27 patients receiving aprepitant on study were evaluated. By the end of Day 5, 3/27 patients (11%) had experienced at least one episode of vomiting or retching, while by the end of Day 8 four additional patients had experienced vomiting/retching, for a cumulative incidence of 26%. In comparison, the cumulative incidence of vomiting or retching by the end of Day 5 in the retrospective cohort was 50% (20/40), and 53% by Day 8. The proportion of patients experiencing vomiting was below 8% per day on aprepitant dosing days, but increased to11% on Day 6.  The cumulative incidence of nausea and/or vomiting in the aprepitant group was 52% by the end of Day 5 and 60% at the end of Day 8, as compared to 78% at both time points in the retrospective cohort. There were no toxicities attributable to aprepitant. Conclusion The results indicate that aprepitant is highly effective, when combined with a 5-HT3 antagonist, in preventing vomiting in patients receiving AML induction chemotherapy with 3+7. The combination appears less effective in controlling nausea. The results warrant further evaluation in a Phase III randomized placebo controlled study. Disclosures: Brandwein: Merck: Honoraria, Research Funding. Off Label Use: Aprepitant as anti-emetic prophylaxis for AML induction. Seki:Merck: Honoraria.

Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5506-5506 ◽  
Author(s):  
Richard T. Penson ◽  
Ricardo Villalobos Valencia ◽  
David Cibula ◽  
Nicoletta Colombo ◽  
Charles A. Leath ◽  
...  
Keyword(s):  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Platinum Sensitive ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Platinum Chemotherapy

5506 Background: Data from a randomized Phase II trial (NCT00628251) of olaparib (capsules, 200 or 400 mg bid, n=32 per arm) vs pegylated liposomal doxorubicin (PLD, n=33) in gBRCAm OC pts with recurrence ≤12 months after prior platinum therapy indicated efficacy for olaparib (Kaye et al. JCO 2012). However, the efficacy of PLD was higher than previously reported in this setting. We led a confirmatory Phase III, open-label study of olaparib vs non-platinum chemotherapy in gBRCAm PSR OC pts (NCT02282020). Methods: Pts were randomized (2:1) to olaparib tablets (300 mg bid) or chemotherapy treatment of physician’s choice (TPC) (paclitaxel [P; 80 mg/m2 on day 1 (D1), D8, D15, D22 every 4 weeks (q4w)], topotecan [T; 4 mg/m2 D1, D8, D15 q4w], gemcitabine [G; 1000 mg/m2 D1, D8, D15 q4w] or PLD [50 mg/m2 D1 q4w]) until progression, stratified by: TPC, prior lines of chemotherapy (2–3 vs ≥4) and platinum-free interval (6–12 vs >12 months). Primary endpoint: ORR (blinded independent central review [BICR]). Secondary endpoints included PFS and safety. Results: 266 gBRCAm PSR OC pts were randomized (olaparib, n=178; TPC, n=88 [ PLD, n=47; P, n=20; G, n=13; T, n=8]); 12 in the TPC arm withdrew before receiving study treatment. 223 pts (84%) had baseline BICR measurable disease (olaparib, n=151; TPC, n=72). ORR was 72% with olaparib vs 51% with TPC (OR 2.53, 95% CI 1.40–4.58; P=0.002). HR for PFS by BICR was 0.62 (95% CI 0.43–0.91; P=0.013; median 13.4 vs 9.2 months [olaparib vs TPC]) and by investigator assessment was 0.49 (95% CI 0.35–0.70; P<0.001; median 13.2 vs 8.5 months, respectively). Most common adverse events (AEs) with olaparib were nausea (65% vs 34% [TPC]) and anemia (50% vs 25%) and with TPC were palmar-plantar erythrodysesthesia (PPE; 36% vs 1% [olaparib]) and nausea. Most common grade ≥3 AEs in either arm were anemia (21% [olaparib] vs 0 [TPC]), PPE (0 vs 12%) and neutropenia (6% vs 11%). For olaparib vs TPC, serious AEs were reported by 24% vs 18% and AEs led to treatment discontinuation in 7% vs 20%. Conclusions: Pts with gBRCAm PSR OC receiving olaparib monotherapy had a significant, clinically relevant improvement in ORR and PFS vs TPC, with no new safety signals. Clinical trial information: NCT02282020.

Efficacy and Safety of Plastic Cannulae Compared with Metal Needles in the Initial Use of an Arteriovenous Fistulae in Incident Hemodialysis Patients: A Randomized Controlled Study

2021 ◽  
pp. 1-8
Author(s):  
Yong Seon Choi ◽  
Hyung Seok Lee ◽  
Narae Joo ◽  
Pyoungju Park ◽  
Seung Nam Cho ◽  
...  
Keyword(s):  
Controlled Study ◽  
Open Label ◽  
Open Label Study ◽  
Vessel Injury ◽  
Secondary Endpoints ◽  
Metal Group ◽  
A New Technique ◽  
Difficulty Score ◽  
Metal Needle

<b><i>Introduction:</i></b> Successful cannulation of an arteriovenous fistula (AVF) is important in patients starting hemodialysis (HD). Metal needles have been used for decades, but the usefulness of plastic cannulae has recently been demonstrated as a new technique. <b><i>Methods:</i></b> This was a prospective, randomized, open-label study of incident HD patients. Eligible patients were randomized into 2 groups in a 1:1 ratio (<i>n</i> = 45/group). Maturation of the AVF was confirmed using Doppler ultrasound prior to first needling, and 2 well-trained nurses implemented the AVF cannulation. The primary endpoint was the initial cannulation failure rate, defined as the failure of successful completion of 3 consecutive dialysis sessions. The secondary endpoints were time for hemostasis at the end of HD, degree of patients’ pain, degree of cannulation difficulty felt by the nursing staffs, and achieving optimal HD adequacy. <b><i>Results:</i></b> The mean elapsed time from AVF creation to the first cannulation was 48.1 ± 16.7 days. A total of 17 cases of cannulation failure occurred, and the failure risk tended to be higher in the metal needle group than the plastic cannula group (hazard ratio 2.6, 95% confidence interval 0.95–7.41) after adjusting for age, gender, comorbidities, and AVF location. The overall incidence of vessel injury was higher and time for hemostasis was significantly longer in the metal group than the plastic group. The use of plastic cannula was associated with a better HD adequacy compared to a metal needle. However, the patients’ pain score (<i>p</i> = 0.004) and nursing staff’s cannulation difficulty score (<i>p</i> = 0.084) were higher in the plastic group, emphasizing the great importance of practice using plastic cannulae. <b><i>Conclusion:</i></b> The vascular outcomes of plastic cannulae were much favorable compared to metal needles in incident HD patients. The use of plastic cannulae could be a new and innovative way to improve the quality of dialysis.

A phase II open-label study of aprepitant as anti-emetic prophylaxis in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy

2018 ◽  
Vol 27 (6) ◽  
pp. 2295-2300 ◽  
Author(s):  
Joseph M. Brandwein ◽  
Jack T. Seki ◽  
Eshetu G. Atenafu ◽  
Amr Rostom ◽  
Andrzej Lutynski ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Myeloid Leukemia ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Acute Myeloid

A phase II study of ziv-aflibercept (Z) + FOLFIRI in Japanese patients (pts) with metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 707-707 ◽  
Author(s):  
Taroh Satoh ◽  
Tadamichi Denda ◽  
Tetsuya Hamaguchi ◽  
Naotoshi Sugimoto ◽  
Takashi Ura ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Complete Response ◽  
Japanese Patients ◽  
Phase Iii ◽  
Open Label ◽  
Secondary Endpoints ◽  
Phase Iii Study

707 Background: VEGF promotes tumor angiogenesis and metastasis. Z blocks the activity of VEGF-A/-B, and placental growth factor and was shown in the VELOUR phase III study (NCT00561470) outside of Japan to significantly improve overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) in mCRC pts as a second-line treatment given with FOLFIRI. Goals of the current open-label, multicenter phase II study were to assess the efficacy and safety of Z + FOLFIRI in a post-oxaliplatin setting in mCRC pts in Japan. Methods: Pts received Z (4 mg/kg) + FOLFIRI (400 mg/m2 bolus 5-fluorouracil [FU]; 2400 mg/m2 continuous infusion 5-FU; 200 mg/m2 levofolinate; 180 mg/m2 irinotecan) every 2 weeks until progression, unacceptable toxicity, or study withdrawal. Primary endpoint: ORR (required 60 pts in order to obtain a 95% CI width of 16–20%, assuming an ORR of 10–20%). Secondary endpoints: PFS, OS, and safety. Tumors were assessed by independent reviewers every 6 ± 1 weeks until progression. Results: Study enrolled 62 pts; 50 pts (83.3%) had received prior bevacizumab. Of 60 pts evaluable for response, 5 had a partial response and none had a complete response, resulting in an ORR of 8.3% (95% CI: 1.3–15.3%). The median PFS was 5.42 months (95% CI: 4.140–6.702), and the median OS was 15.59 months (range 11.20–19.81). Forty-one pts (66.1%) died due to progression; none died due to study treatment. Pts underwent a median of 8 treatment cycles (range 1–31) lasting a median of 21.8 weeks (range 2–73). The median relative dose intensity was 0.99 (range 0.2–1.0) for Z, 0.87 (range 0.4–1.0) for irinotecan, and 0.96 (range 0.7–1.0) for 5-FU. All pts had ≥1 treatment emergent adverse event (TEAE; see table). Conclusions: The ORR was 8.3% (95% CI: 1.3–15.3%), and the median OS was 15.59 months. The safety profile was consistent with that reported previously. Registered as NCT01882868. Clinical trial information: NCT01882868. [Table: see text]

scholarly journals P131 Efficacy and safety of olokizumab in a phase III trial of patients with moderately to severely active RA inadequately controlled by methotrexate: placebo and active controlled study

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Eugen Feist ◽  
Saima Chohan ◽  
Saeed Fatenejad ◽  
Sergey Grishin ◽  
Elena Korneva ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomised Clinical Trial ◽  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Acr20 Response ◽  
Phase Iii Trial ◽  
Secondary Endpoints

Abstract Background/Aims  Olokizumab (OKZ) is a new humanised monoclonal antibody targeting IL-6 directly. Here we present the results of a global randomised clinical trial (RCT) in patients (pts) with RA. Methods  This double-blind, placebo (PBO) and active controlled, RCT in pts with moderately to severely active RA despite MTX (ClinicalTrials.gov Identifier NCT02760407, CREDO2) was carried out in 18 counties. Pts were randomized 2:2:2:1 to receive subcutaneous injections of OKZ 64 mg every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w), adalimumab (ADA) 40mg q2w or PBO for 24 weeks, plus MTX. After week 24, subjects either rolled over into an open-label study or entered the Safety Follow-Up Period for another 20 weeks. The primary endpoint was ACR 20% (ACR20) response rate at week 12. Secondary endpoints included: percentage of subjects with DAS28-CRP &lt;3.2 and improvement of HAQ-DI from baseline at week 12, ACR50 and percentage of subjects with remission (CDAI) ≤2.8 at week 24. Safety outcomes, including adverse events, serious adverse events and laboratory abnormalities were assessed. Results  1,648 subjects were randomised to OKZ 64mg q2w (n = 464), OKZ 64mg q4w (n = 479), ADA 40mg (n = 462) or PBO (n = 243). Baseline characteristics were comparable across treatment arms. The vast majority of the pts completed 24 weeks treatment period 421 (90.7%) in q2w, 437 (91.2%) in q4w, 413 (89.4%) in ADA and 208 (85.6%) in PBO arms and enrolled to open-label extension study: 410 (88.4%), 422 (88.1%), 397 (85.9%) and 199 (81.9%) pts, respectively. Both regimens of OKZ were significantly better than PBO in all primary and secondary endpoints. Furthermore, non-inferiority to ADA was demonstrated for the pre-defined endpoints of ACR20 and DAS28-CRP&lt;3.2 for both OKZ treatment groups. The efficacy outcomes were maintained throughout the 24-week period of the study. Overall incidence of treatment-emergent adverse events (TEAEs) was 70.0% in OKZ q2w arm; 70.9% in OKZ q4w arm, 65.4% in ADA arm and 63.4% in PBO, TEAEs leading to study treatment discontinuation were reported in 4.5%, 6.3%, 5.6% and 3.7% pts, respectively. The number of deaths were comparable among arms: 3 (0.6%; 2 infections, 1 cerebrovascular accident) in the OKZ q2w arm, 2 (0.4%; 1 infection, 1 myocardial ischemia) in OKZ q4w arm, 1 (0.2%; infection) in ADA arm and 1 (0.4%; sudden death) in PBO. The most common treatment-emergent serious adverse events (TESAEs) were infections. Conclusion  In this global Phase III trial, treatment with OKZ plus MTX in both regimes (OKZ 64 mg q2w and OKZ 64 mg q4w) was associated with significant improvements in the signs, symptoms and physical function of RA compared to PBO plus MTX and non-inferior to ADA plus MTX over a 24-week period. OKZ was well tolerated and no new safety signals were observed. Disclosure  E. Feist: Consultancies; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi. Honoraria; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Member of speakers’ bureau; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Grants/research support; Lilly, Novartis, Pfizer, Roche/Chugai. S. Chohan: None. S. Fatenejad: Consultancies; RPharm International. Shareholder/stock ownership; Pfizer. S. Grishin: Corporate appointments; Employed by R-Pharm. E. Korneva: Corporate appointments; Employed by R-Pharm. E.L. Nasonov: Honoraria; Lilly, Abbnie, Prizer, Biocad, R-Pharm. Member of speakers’ bureau; Lilly, Abbnie, Prizer, Biocad, R-Pharm. A. Rowińska-Osuch: Consultancies; R-Pharm. M. Samsonov: Corporate appointments; Employed by R-Pharm.

A Phase II Study of Low-Dose Pomalidomide (0.5mg/day) and Prednisone Combination Therapy in Patients with Myelofibrosis and Significant Anemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1728-1728
Author(s):  
Aditi Shastri ◽  
Jorge E. Cortes ◽  
Elias J. Jabbour ◽  
Lingsha Zhou ◽  
Kurt Schroeder ◽  
...  
Keyword(s):  
Phase Ii ◽  
Low Dose ◽  
Single Agent ◽  
Median Number ◽  
Jak2v617f Mutation ◽  
Phase Iii ◽  
Controlled Study ◽  
Delphi Consensus ◽  
Open Label ◽  
Rbc Transfusion

Abstract Abstract 1728 Introduction: Pomalidomide (POM) is an investigational immunomodulatory drug (IMID) that has shown efficacy in preliminary studies, with or without prednisone, as therapy for myelofibrosis (MF) with anemia, by eliminating the need for red blood cell (RBC) transfusions. In our experience, however, single agent low dose POM (0.5 mg/d) has very modest efficacy in achieving RBC transfusion independence in MF patients (Shastri A et al Blood 2011; 118). To further understand and define its activity, we have undertaken a single center phase II open label study to assess the efficacy of low dose POM in combination with prednisone therapy. In a prior study this combination resulted in a 36% response rate according to International Working Group for Myelofibrosis Research and Therapy (IWG-MRT) response criteria (Tefferi A, et al. JCO 2009; 27:4563). In the current study, benefit was assessed by the RAND-Delphi consensus criteria, which has been suggested as a better tool to evaluate RBC transfusion dependence/independence in clinical trials (Gale RP et al. Leuk Res 2011; 35:8) than IWG-MRT criteria. Patients were also evaluated for an increase in hemoglobin of at least 2g/dL for duration of 8 weeks, without transfusion support. Patients & Results: 21 patients, 14 male and 7 female, were enrolled in the study: 2 (10%) had post essential thrombocythemia MF, and 19 (90%) had primary MF. Median age was 69 years (range 48–85) and 15 (71%) were previously treated; 5 had been treated with other IMIDs previously. Four (19%) had splenomegaly; 1 had prior splenectomy. Seven (33%) had abnormal cytogenetics and 10 (48%) had JAK2V617F mutation. All patients had hemoglobin <10g/dL at study entry; patients with higher hemoglobin that were transfusion dependent were allowed to enroll if it was a result of a blood transfusion given just prior to enrollment. Median hemoglobin was 8.5 g/dL (range 7.3–11.1), WBC 4.7×109/L (1–20.7), and platelets 155×109/L (35–1191). The use of anagrelide during the study was allowed to control high platelets, if indicated; other concomitant therapies, including growth factors, were not allowed. Patients were administered POM 0.5mg continuously daily in 28-day cycles and prednisone was administered as 30mg daily for the first month, 15mg daily for second month, 15mg every other day for third month and then stopped. Thirteen (62%) patients were transfusion dependent by the RAND-Delphi consensus criteria. After a median follow up of 7.8 months (3.3–11.9), 6 (28%) patients were still on the therapy. The median number of cycles administered to patients was 6 (2–12). Fourteen patients were taken off the study for lack of response (N=12) or for loss of a response (N=2). One patient was taken off due to the development of grade 3 pneumonitis. Three died from unrelated causes. Three patients were noted to have RBC transfusion response per RAND-Delphi criteria. One of the responders had JAK2V617F mutation. Median time to response was 52.7 days (48 – 55 days). No patient had an increase in hemoglobin of at least 2g/dL for at least 8 weeks. This is an ongoing trial and updated results along with complete toxicity profile will be presented at the meeting. Conclusion: POM administered in combination with prednisone to patients with MF and significant anemia has modest efficacy, comparable to single agent POM. A Phase III blinded, placebo-controlled study is underway globally for MF patients with significant anemia and RBC transfusion dependency. Disclosures: Verstovsek: Celgene: Research Funding.

scholarly journals Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study

2020 ◽  
Vol 8 (1) ◽  
pp. e000773
Author(s):  
Carol H Wysham ◽  
Julio Rosenstock ◽  
Marion L Vetter ◽  
Hui Wang ◽  
Elise Hardy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Registration Number ◽  
Efficacy Measures ◽  
Design And Methods ◽  
To Receive

IntroductionInvestigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year.Research design and methodsIn this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight.ResultsIn total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28–52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of –1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of –1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks.ConclusionsSwitching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns.Trial registration numberNCT01652716.

485 Efficacy and Safety of Once- and Twice-Nightly Dosing of Lower-Sodium Oxybate in Adults With Idiopathic Hypersomnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A191-A192
Author(s):  
Isabelle Arnulf ◽  
Anne Marie Morse ◽  
Patricia Chandler ◽  
Rupa Parvataneni ◽  
Dan Chen ◽  
...  
Keyword(s):  
Sodium Oxybate ◽  
Mean Difference ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Patient Global Impression ◽  
Idiopathic Hypersomnia ◽  
Secondary Endpoints ◽  
Global Impression Of Change

Abstract Introduction Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder. In a randomized, controlled study of lower-sodium oxybate (LXB; Xywav™) in adults with IH (NCT03533114), significant differences for LXB compared with placebo were observed in Epworth Sleepiness Scale (ESS; primary efficacy endpoint), self-reported Patient Global Impression of Change (PGIc), and IH Severity Scale (IHSS; key secondary endpoints). In this clinical study, investigators were permitted to initiate LXB dosing on a once-nightly or twice-nightly regimen. Methods Eligible participants aged 18–75 years began LXB treatment, administered once or twice nightly during an open-label treatment/titration and optimization period (OLTTOP; 10–14 weeks); dose amount/regimen could be adjusted during this period. Participants next entered a 2-week, open-label, stable-dose period (SDP), then were randomized to placebo or to continue LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). P values are nominal for this exploratory analysis. Results Of 154 enrolled participants, 40 (26%) initiated LXB treatment on a once-nightly regimen. In the efficacy population (n=115), 27 participants were on a once-nightly regimen during SDP (48.1% of whom initiated treatment once nightly during OLTTOP) and 88 participants were on a twice-nightly regimen during SDP (86.4% of whom initiated treatment twice nightly during OLTTOP). During SDP, median (min, max) LXB total dose was 4.5 (2.5, 6) g/night (once-nightly group) and 7.5 (4.5, 9) g/night (twice-nightly group). ESS scores worsened in participants randomized to placebo vs those continuing LXB in the once-nightly group (n=11 and n=15, respectively; LS mean difference [95% CI]: −4.93 [−7.41, −2.46]; P=0.0004) and twice-nightly group (n=47 and n=41, respectively; LS mean difference [95% CI]: −7.44 [−9.15, −5.72]; P&lt;0.0001). Worsening was also observed in PGIc (once-nightly: 81.8% [placebo] vs 26.7% [LXB]; P=0.0077; twice-nightly: 89.4% [placebo] vs 19.5% [LXB]; P&lt;0.0001) and IHSS score (estimated median difference [95% CI], once-nightly: −9.00 [−16.0, −3.0]; P=0.0028; twice-nightly: −12.00 [−15.0, −8.0]; P&lt;0.0001). Common adverse events included nausea (21.4%), headache (16.2%), anxiety (14.9%), dizziness (11.7%), insomnia (11.7%), and vomiting (10.4%). Conclusion The efficacy and safety of LXB in IH were demonstrated for both once-nightly and twice-nightly regimens. The majority of participants initiated and remained on a twice-nightly regimen. Support (if any) Jazz Pharmaceuticals

scholarly journals A Pharmacological Batch of Mongersen that Downregulates Smad7 is Effective as Induction Therapy in Active Crohn’s Disease: A Phase II, Open-Label Study

BioDrugs ◽  
2021 ◽  
Vol 35 (3) ◽  
pp. 325-336
Author(s):  
Irene Marafini ◽  
Carmine Stolfi ◽  
Edoardo Troncone ◽  
Elisabetta Lolli ◽  
Sara Onali ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Phase Ii ◽  
Induction Therapy ◽  
Open Label ◽  
Open Label Study ◽  
Label Study
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