P.027 Efficacy and Safety of Eptinezumab Initiated During a Migraine
                        Attack: Results from the RELIEF Study

Background: Eptinezumab is approved for migraine prevention, with demonstrated rapid onset of preventive benefit. RELIEF evaluated the efficacy and safety of eptinezumab initiated during a migraine attack. Methods: RELIEF (NCT04152083; parallel-group, double-blind, placebo-controlled) randomized adults with migraine (4-15d/mo in 3mo prior to screening) to eptinezumab 100mg or placebo, administered IV within 1-6h of qualifying migraine onset. Co-primary efficacy endpoints were time to headache pain freedom and time to absence of most bothersome symptom (MBS). Results: Eptinezumab (n=238) compared with placebo (n=242) achieved significantly faster headache pain freedom (median 4h vs 9h; hazard ratio=1.54, P=0.0006) and absence of MBS (2h vs 3h; 1.75, P<0.0001). At 2h, 23.5% and 12.0% (P=0.0009) of eptinezumab-treated and placebo patients, respectively, reported headache pain freedom, and 55.5% and 35.8% (P<0.0001) reported absence of MBS. Significantly fewer eptinezumab-treated patients used rescue medication within 24h (31.5% vs 59.9%; P<0.0001). Treatment-emergent adverse events occurred in 10.9% eptinezumab-treated and 10.3% placebo patients; no serious adverse events occurred. Conclusions: Infusion of the preventive migraine treatment, eptinezumab, during a migraine resulted in rapid and sustained freedom from headache pain and MBS vs placebo, starting 2h post-infusion, decreasing need for acute medication within 24h post-infusion. No notable safety findings were identified.

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Sumatriptan nasal spray for the acute treatment of migraine

Neurology ◽

10.1212/wnl.49.5.1225 ◽

1997 ◽

Vol 49 (5) ◽

pp. 1225-1230 ◽

Cited By ~ 79

Author(s):

R. Ryan ◽

A. Elkind ◽

C. C. Baker ◽

W. Mullican ◽

S. DeBussey ◽

...

Keyword(s):

Adverse Events ◽

Migraine Attack ◽

Nasal Spray ◽

Acute Treatment ◽

International Headache Society ◽

Migraine Treatment ◽

Multicenter Studies ◽

Double Blind ◽

Treatment Groups ◽

Migraine Medication

Background: Sumatriptan nasal spray may be particularly useful for patients whose nausea and vomiting preclude them from using oral migraine medication or for patients who prefer not to use an injectable migraine medication. The objective of this study was to evaluate in two clinical studies the efficacy and tolerability of the intranasal form of sumatriptan in the acute treatment of a single migraine attack. International Headache Society-diagnosed adult migraineurs in two randomized, double-blind, parallel-group, multicenter studies (n = 409 and 436) used sumatriptan nasal spray 20 mg, 10 mg, or placebo (2:1:1) for the acute treatment of a single migraine attack at home. Predose and at predetermined postdose intervals, patients recorded headache severity (none, mild, moderate, severe); time to meaningful relief; clinical disability (none, mildly impaired, severely impaired, bed rest required); presence/absence of nausea, photophobia, and phonophobia; and the occurrence of adverse events. Two hours postdose in the two studies, moderate or severe baseline pain was reduced to mild or none in 62 to 63% of patients treated with sumatriptan 20 mg, 43 to 54% of patients treated with sumatriptan 10 mg, and 29 to 35% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies and 10 mg versus placebo for study 1). Onset of relief relative to placebo began as early as 15 minutes postdose(sumatriptan 20 mg, study 2). Clinical disability at 2 hours postdose was reported as mildly impaired or normal in 72 to 74% of patients treated with sumatriptan 20 mg, 56 to 68% of patients treated with sumatriptan 10 mg, and 47 to 58% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. The most common adverse event in the active treatment groups was disturbance of taste (bad, bitter, or unpleasant taste). Aside from this event, the pattern and incidence of adverse events did not differ among treatment groups. From these results we determined that sumatriptan nasal spray is a rapidly effective, well-tolerated migraine treatment. The 20-mg dose was effective in treating the entire migraine symptom complex, and the 10-mg dose was less consistently effective.

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Sertraline in the treatment of panic disorder

The British Journal of Psychiatry ◽

10.1192/bjp.173.1.54 ◽

1998 ◽

Vol 173 (1) ◽

pp. 54-60 ◽

Cited By ~ 87

Author(s):

Peter D. Londborg ◽

Robert Wolkow ◽

Ward T. Smith ◽

Eugene Duboff ◽

Donald England ◽

...

Keyword(s):

Panic Disorder ◽

Adverse Events ◽

Drop Out ◽

Panic Attacks ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Hamilton Anxiety Scale ◽

Higher Doses ◽

Clinical Global Impression Improvement

BackgroundThis study compared the efficacy and safety of sertraline to placebo in treating panic disorder.Method178 out-patients with panic disorder who exhibited at least four panic attacks during the four weeks prior to screening and three during the two weeks of lead-in were randomly assigned to 12 weeks of double-blind treatment with sertraline (50, 100 or 200 mg) or placebo.ResultsSertraline was superior to placebo in reducing the number of panic attacks, situational attacks, unexpected attacks, limited symptom attacks, and time spent worrying (all P < 0.01) and the Hamilton Anxiety Scale (P < 0.05), although Clinical Global Impression (Improvement) did not significantly differentiate groups at 12 weeks and at end-point. No serious adverse events were associated with sertraline. No dose relationship was found for adverse events; overall drop-out rates were not different for sertraline or placebo, although more sertraline-treated subjects discontinued for adverse events, typically early in the study. Only dry mouth and ejaculation failure (primarily ejaculation delay) were associated significantly with sertraline. Conclusions Sertraline was effective and safe in reducing panic attacks. Higher doses were no more effective than the 50 mg dose.

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Duloxetine in the Treatment of Stress Urinary Incontinence

Women s Health ◽

10.2217/17455057.1.3.345 ◽

2005 ◽

Vol 1 (3) ◽

pp. 345-358 ◽

Cited By ~ 6

Author(s):

Martin C Michel ◽

Matthias Oelke

Keyword(s):

Urinary Incontinence ◽

Stress Urinary Incontinence ◽

Adverse Events ◽

Striated Muscle ◽

Bladder Capacity ◽

Efficacy And Safety ◽

Cytochrome P450 1A2 ◽

Serious Adverse Events ◽

Double Blind ◽

Urethral Striated Muscle

This manuscript reviews the pharmacodynamics and pharmacokinetics of duloxetine and its efficacy and safety in women with stress urinary incontinence. Duloxetine is a selective inhibitor of neuronal serotonin and norepinephrine uptake which increases urethral striated muscle activity and bladder capacity. Duloxetine is readily absorbed and extensively metabolized; cytochrome P450 1A2 (CYP1A2) inhibiting drugs can markedly increase duloxetine exposure. The clinical efficacy of duloxetine has consistently been demonstrated in several randomized, double-blind studies in women with moderate-to-severe stress urinary incontinence, but the additional benefit relative to placebo was moderate. Duloxetine treatment is frequently associated with adverse events such as nausea, dry mouth, fatigue, insomnia and constipation, but serious adverse events are rare. Therefore, duloxetine appears suitable for the treatment of stress urinary incontinence.

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Efficacy and safety of lipegfilgrastim compared with pegfilgrastim in patients with breast cancer who are receiving chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e19587 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e19587-e19587

Author(s):

Igor Bondarenko ◽

Oleg Gladkov ◽

Reiner Elaesser ◽

Anton Buchner ◽

Peter Bias

Keyword(s):

Breast Cancer ◽

Febrile Neutropenia ◽

Adverse Events ◽

Stage Ii ◽

Severe Neutropenia ◽

Study Medication ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Increased Risk

e19587 Background: Cancer chemotherapy frequently causes neutropenia, leading to an increased risk of infections and delays in subsequent chemotherapy treatments. Pegfilgrastim is a pegylated recombinant form of granulocyte colony stimulating factor (G-CSF) that extends the half-life and requires less frequent dosing than nonpegylated G-CSF. Lipegfilgrastim is a glycosylated and pegylated G-CSF. The objective of this study was to compare the efficacy and safety of lipegfilgrastim and pegfilgrastim in chemotherapy-naïve patients with breast cancer who are candidates to receive docetaxel/doxorubicin. Methods: In this double-blind, randomized, active-controlled, noninferiority trial, patients with high-risk stage II, III, or IV breast cancer and an absolute neutrophil count ≥1.5x109 cells/L were randomly assigned to lipegfilgrastim 6 mg (n=101) or pegfilgrastim 6 mg (n=101). Study medication was injected subcutaneously on day 2 of the chemotherapy cycle (4 cycles maximum). Primary efficacy endpoint was the duration of severe neutropenia (days with an absolute neutropenia count <0.5x109 cells/L) during cycle 1. Secondary endpoints included the incidence of febrile neutropenia. Efficacy analysis population included patients who were randomized but did not have major protocol violations. Results: Overall, 37%, 46%, and 17% of patients had stage II, III, and IV breast cancer, respectively. The mean duration of severe neutropenia in cycle 1 was 0.7 days in the lipegfilgrastim group and 0.8 days in the pegfilgrastim group (poisson regression least squares mean [95% CI] -0.218 [-0.498 to 0.062]). 56% and 49%, respectively, did not experience severe neutropenia in cycle 1. Three patients experienced febrile neutropenia; all were in the pegfilgrastim group during cycle 1. 28% of patients in the lipegfilgrastim group and 26% in the pegfilgrastim group had adverse events that the investigator considered to be related to study medication. Three and 7 patients, respectively had serious adverse events. Conclusions: The results of this study confirm that the efficacy of lipegfilgrastim is comparable with pegfilgrastim. No unexpected safety events were observed.

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Lasmiditan is an effective acute treatment for migraine

Neurology ◽

10.1212/wnl.0000000000006641 ◽

2018 ◽

Vol 91 (24) ◽

pp. e2222-e2232 ◽

Cited By ~ 92

Author(s):

Bernice Kuca ◽

Stephen D. Silberstein ◽

Linda Wietecha ◽

Paul H. Berg ◽

Gregory Dozier ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Migraine Attack ◽

Acute Treatment ◽

Adult Patients ◽

Electronic Diary ◽

Double Blind ◽

Bothersome Symptom ◽

Headache Pain

ObjectiveTo assess the efficacy and safety of lasmiditan in the acute treatment of migraine.MethodsAdult patients with migraine were randomized (1:1:1) to a double-blind dose of oral lasmiditan 200 mg, lasmiditan 100 mg, or placebo and were asked to treat their next migraine attack within 4 hours of onset. Over 48 hours after dosing, patients used an electronic diary to record headache pain and the presence of nausea, phonophobia, and photophobia, one of which was designated their most bothersome symptom (MBS).ResultsOf the 1,856 patients who treated an attack, 77.9% had ≥1 cardiovascular risk factors in addition to migraine. Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0–3.6, p< 0.001), similar to those dosed with lasmiditan 100 mg (28.2%; OR 2.2, 95% CI 1.6–3.0, p< 0.001). Furthermore, compared with those dosed with placebo, more patients dosed with lasmiditan 200 mg (40.7% vs 29.5%; OR 1.6, 95% CI 1.3–2.1, p< 0.001) and lasmiditan 100 mg (40.9%; OR 1.7, 95% CI, 1.3–2.2, p< 0.001) were free of their MBS at 2 hours after dosing. Adverse events were mostly mild or moderate in intensity.ConclusionsLasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors.ClinicalTrials.gov identifierNCT02439320.Classification of evidenceThis study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack.

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Five-year Efficacy and Safety of Tocilizumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Methotrexate- and Biologic-naive or Free of Methotrexate for 6 Months: the AMBITION Study

The Journal of Rheumatology ◽

10.3899/jrheum.160287 ◽

2016 ◽

Vol 44 (2) ◽

pp. 142-146 ◽

Cited By ~ 11

Author(s):

Graeme Jones ◽

Thomas Wallace ◽

Matthew J. McIntosh ◽

Laura Brockwell ◽

Juan J. Gómez-Reino ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Link Type ◽

Serious Infection ◽

Tocilizumab Monotherapy ◽

Safety Signals

Objective.To report on the 5-year efficacy and safety results of the AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) monotherapy study (ClinicalTrials.gov: NCT00109408, NCT00720798).Methods.Patients with rheumatoid arthritis for whom biologics had not failed or who did not discontinue methotrexate because of lack of efficacy or tolerability were followed up for 5 years to assess the efficacy and serious adverse events (SAE) of tocilizumab (TCZ) monotherapy.Results.Longterm efficacy results showed that efficacy was maintained or improved for up to 264 weeks in patients receiving TCZ monotherapy. Serious infection was the most frequent SAE; no new safety signals were reported.Conclusion.Longterm monotherapy with TCZ demonstrated continuing efficacy and safety.

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Efficacy and safety of short-term therapy with indigo naturalis for ulcerative colitis: An investigator-initiated multicenter double-blind clinical trial

PLoS ONE ◽

10.1371/journal.pone.0241337 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0241337

Author(s):

Kan Uchiyama ◽

Shinichiro Takami ◽

Hideo Suzuki ◽

Kiyotaka Umeki ◽

Satoshi Mochizuki ◽

...

Keyword(s):

Ulcerative Colitis ◽

Placebo Group ◽

Adverse Events ◽

Efficacy And Safety ◽

Short Term ◽

Serious Adverse Events ◽

Double Blind ◽

Multicenter Randomized Controlled Trial ◽

Highly Effective ◽

Indigo Naturalis

Introduction Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. Objective We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. Methods A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5–10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. Results The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. Conclusions Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.

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Efficacy and safety of balugrastim compared with pegfilgrastim in patients with breast cancer who are receiving chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9125 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9125-9125 ◽

Cited By ~ 1

Author(s):

Constantin D. Volovat ◽

Oleg Gladkov ◽

Igor Bondarenko ◽

Steven Barash ◽

Anton Buchner ◽

...

Keyword(s):

Breast Cancer ◽

Febrile Neutropenia ◽

Adverse Events ◽

Severe Neutropenia ◽

Comparable Efficacy ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Increased Risk ◽

Long Acting

9125 Background: Patients receiving cancer chemotherapy are at an increased risk of neutropenia. Recombinant granulocyte colony stimulating factors (G-CSFs) have been developed to stimulate proliferation and differentiation of neutrophils. Pegfilgrastim is a pegylated recombinant G-CSF that allows for once-per-cycle dosing. Balugrastim is a long-acting G-CSF composed of a genetic fusion between recombinant human serum albumin and G-CSF. The objective of this study was to compare the efficacy and safety of balugrastim and pegfilgrastim in patients with histologically or cytologically confirmed breast cancer who were scheduled to receive doxorubicin and docetaxel. Methods: In this double-blind, randomized, active-comparator, noninferiority trial, patients with ≥1.5x109 neutrophils/L, and ≥100x109 platelets/L were randomly assigned to subcutaneous injections of balugrastim 40 mg (n=153) or pegfilgrastim 6 mg (n=151) with stratifications for weight, prior chemotherapy exposure, and global location. The primary efficacy endpoint was the duration of severe neutropenia (days with an absolute neutrophil count <0.5x109 cells/L) during the cycle 1 for the population of patients who did not have major protocol violations. Results: Mean duration of severe neutropenia in cycle 1 was 1.1 days in the balugrastim group and 1.0 days in the pegfilgrastim group (95% CI for difference between groups -0.13 to 0.37). Fifty-eight percent of patients in the balugrastim group and 59% in the pegfilgrastim group had severe neutropenia during cycle 1 (95% CI for difference between groups -11.98% to 10.41%). Two and 4 patients, respectively, had febrile neutropenia during cycle 1; no patients in either group had febrile neutropenia during cycles 2-4. Twenty percent of patients in the balugrastim group and 19% in the pegfilgrastim group had adverse events that the investigator considered to be related to study medication. Six and 7 patients, respectively, had serious adverse events. Conclusions: The results of this study support the noninferiority of balugrastim versus pegfilgrastim, demonstrating that both compounds have comparable efficacy. There were no unexpected safety events.

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Cardiovascular outcomes in adults with migraine treated with eptinezumab for migraine prevention: pooled data from four randomized, double-blind, placebo-controlled studies

The Journal of Headache and Pain ◽

10.1186/s10194-021-01360-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Timothy R. Smith ◽

Egilius L. H. Spierings ◽

Roger Cady ◽

Joe Hirman ◽

Anders Ettrup ◽

...

Keyword(s):

Blood Pressure ◽

Clinical Trials ◽

Adverse Events ◽

Vital Signs ◽

Primary Objective ◽

Cardiovascular Outcomes ◽

Migraine Treatment ◽

Serious Adverse Events ◽

Double Blind ◽

Link Type

Abstract Background Patients with migraine have an increased relative risk of cardio- and cerebrovascular events, and some migraine treatments may exacerbate this risk. The primary objective of this analysis was to determine whether the rate of cardiovascular adverse events was higher for patients with migraine treated with the migraine-preventive eptinezumab, compared with patients receiving placebo. Methods Cardiovascular outcomes in patients with migraine were pooled across four clinical trials (phase 1b, phase 2, and two phase 3 trials) for use of eptinezumab as a preventive migraine treatment for up to 1 year. In all studies, treatment-emergent adverse events (TEAEs) that occurred after the first dose of study treatment (eptinezumab 100 mg, 300 mg, 1000 mg, or placebo) and vital signs were recorded through study completion. Results Cardiovascular TEAEs were rare across all four clinical trials, and rates were similar between patients receiving eptinezumab and those receiving placebo. Cardiovascular TEAEs that did occur were mild or moderate in severity; there were no serious adverse events as per FDA definition. Vital signs (systolic blood pressure, diastolic blood pressure, and heart rate) were not meaningfully different across treatment groups over the course of 56 weeks, compared to placebo. Treatment with eptinezumab did not result in significant new or changed cardiovascular medications used concomitantly compared to placebo. Conclusions In this post hoc analysis of four clinical trials for eptinezumab, doses of 100 mg, 300 mg, and 1000 mg (more than 3 times the highest approved dose) were not associated with clinically relevant changes in vital signs or significant changes in concomitant cardiovascular medication usage, and had low incidences of cardiovascular TEAEs, comparable to placebo. Trial registration NCT01772524 (Study 2), 01/21/2013; NCT02275117 (Study 5), 10/27/2014; NCT02559895 (PROMISE-1), 09/25/2017; NCT02974153 (PROMISE-2), 11/28/2016

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Pilot Study of Droxidopa With Carbidopa in Adults With ADHD

Journal of Attention Disorders ◽

10.1177/1087054715580393 ◽

2015 ◽

Vol 23 (2) ◽

pp. 189-198 ◽

Cited By ~ 7

Author(s):

Lenard A. Adler ◽

Stephen W. Gorny

Keyword(s):

Pilot Study ◽

Adverse Events ◽

Adult Adhd ◽

Adhd Symptoms ◽

Efficacy And Safety ◽

Open Label ◽

Serious Adverse Events ◽

Double Blind ◽

Symptom Report ◽

Pilot Investigation

Objective: We conducted a two-period (open-label and double-blind) pilot investigation of droxidopa, with and without carbidopa, for ADHD. Method: Twenty adult ADHD patients received open-label droxidopa titrated from 200 to 600 mg 3 times per day (TID; Weeks 1-3), then open-label droxidopa plus carbidopa titrated from 25 or 50 mg TID (Weeks 4-6). In Weeks 7 to 8, patients were randomized to continued co-treatment or matching placebo substitution. Results: Improvements in mean total Adult ADHD Investigator Symptom Report Scale (AISRS) scores were seen at Week 1 ( p < .0001) and Week 3 ( p < .0001). Improvements were maintained but not increased with carbidopa. Thirteen of 20 patients completed open-label treatment. In the double-blind period, mean total AISRS scores were similar between the co-treatment ( n = 6) and placebo ( n = 5) groups. No serious adverse events were reported. Conclusion: These preliminary findings indicate that droxidopa can improve adult ADHD symptoms. Further studies are warranted to examine the efficacy and safety of droxidopa in ADHD.

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