Vardenafil demonstrates first-dose success and reliability of penetration and maintenance of erection in men with erectile dysfunction — RELY-II

Objective: Vardenafil has been shown to be efficacious in patients with erectile dysfunction (ED). We evaluated first-dose and repeat-dose response to vardenafil 20 mg.Methods: This randomized, placebo-controlled study consisted of a 4-week, treatment-free run-in phase; a 1-week, open-label challenge phase; and a 12-week, double-blind treatment phase. Primary efficacy was assessed in terms of reliability of insertion based on dose as measured by the Sexual Encounter Profile question 2 (SEP2). We assessed safety by evaluating adverse events (AEs).Results: Baseline patient characteristics in the 2 treatment groups were similar. The most common comorbidities were hypertension (41%), dyslipidemia (28%) and diabetes mellitus (24%). Of the 573 patients receiving the 20-mg vardenafil challenge dose, 464 (81%) achieved first-time successful penetration (SEP2), and 401 (70%) reported successful erection maintenance (SEP3). Patients receiving vardenafil 20 mg had statistically (p < 0.001) and clinically superior SEP2 rates (85%) through weeks 0–12, compared with patients receiving placebo (45%). The increase in reliability of insertion was seen within the first 4 weeks of treatment. Vardenafil therapy was statistically (p < 0.001) and clinically superior to placebo for all secondary efficacy end points as well. Most AEs associated with vardenafil were mild to moderate, with headache, flushing and nasal congestion most frequently reported.Conclusion: Vardenafil 20 mg had a high first-dose success rate for both SEP2 (81%) and SEP3 (70%); this was maintained through to the study end point (85% for SEP2 and 78% for SEP3). These findings were achieved in men with frequentlyassociated comorbidities including hypertension, dyslipidemia and diabetes.

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From clinical guidelines to practice. Clinical experience in treatment of patients with allergic rhinitis

Medical Council ◽

10.21518/2079-701x-2021-18-62-67 ◽

2021 ◽

pp. 62-67

Author(s):

A. Y. Ovchinnikov ◽

N. A. Miroshnichenko ◽

E. M. Khon ◽

N. P. Jimsheleishvili ◽

V. A. Simsovа ◽

...

Keyword(s):

Allergic Rhinitis ◽

Seasonal Allergic Rhinitis ◽

Inflammatory Diseases ◽

Nasal Congestion ◽

Controlled Study ◽

Double Blind ◽

Entire Treatment Period ◽

Treatment Groups ◽

Histamine H1 Receptors ◽

To Receive

Introduction. Antihistamines are the most commonly prescribed class of medications for the treatment of allergic rhinitis (AR). However, they are also widely used in the treatment of inflammatory diseases of the ENT organs. One such drug is levocytirizine, (R) an enantiomer of cetirizine, which is a selective antagonist of peripheral histamine H1-receptors. This article analyzes the properties of levocytirizine in terms of safety and efficacy in allergic rhinitis.Aim of the study is to assess the efficacy of levocetirizine in patients with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) versus placebo, and safety for patients with allergic rhinitis.Materials and methods. In this, double-blind, placebo-controlled study, 52 patients with year-round allergic rhinitis and 28 patients with seasonal allergic rhinitis were randomized to receive levocetirizine 5 mg/day once or placebo. Mean overall measures of five symptoms (nasal congestion, nasal itching, itchy eyes, rhinorrhea, and sneezing) were compared between treatment groups at 1, 2, and 4 weeks. All individual symptom scores were also examined.Results. Levocetirizine showed a significant improvement in the condition of patients with CAR and SAR over the entire treatment period compared to placebo. Assessment of individual symptoms showed statistically significant differences in favor of levocetirizine. Conclusion. Levocetirizine is an effective, safe, and well-tolerated drug for the treatment of allergic rhinitis.

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Co-Administration of Iron and a Bioavailable Curcumin Supplement Increases Serum BDNF Levels in Healthy Adults

Antioxidants ◽

10.3390/antiox9080645 ◽

2020 ◽

Vol 9 (8) ◽

pp. 645 ◽

Cited By ~ 1

Author(s):

Helena Tiekou Lorinczova ◽

Owen Fitzsimons ◽

Leah Mursaleen ◽

Derek Renshaw ◽

Gulshanara Begum ◽

...

Keyword(s):

Iron Supplementation ◽

Energy Homeostasis ◽

Low Dose ◽

Controlled Study ◽

High Dose ◽

Double Blind ◽

Treatment Groups ◽

Novel Approach ◽

First Time ◽

Serum Bdnf

Brain-derived neurotrophic factor (BDNF) is key for the maintenance of normal neuronal function and energy homeostasis and has been suggested to improve cognitive function, including learning and memory. Iron and the antioxidant curcumin have been shown to influence BDNF homeostasis. This 6-week, double blind, randomized, placebo-controlled study examined the effects of oral iron supplementation at low (18 mg) and high (65 mg) ferrous (FS) iron dosages, compared to a combination of these iron doses with a bioavailable formulated form of curcumin (HydroCurcTM; 500 mg) on BDNF levels in a healthy adult cohort of 155 male (26.42 years ± 0.55) and female (25.82 years ± 0.54) participants. Participants were randomly allocated to five different treatment groups: both iron and curcumin placebo (FS0+Plac), low dose iron and curcumin placebo (FS18+Plac), low dose iron and curcumin (FS18+Curc), high dose iron and curcumin placebo (FS65+Plac) and high dose iron and curcumin (FS65+Curc). Results showed a significant increase in BDNF over time (26%) in the FS18+Curc group (p = 0.024), and at end-point between FS18+Curc and FS18+Plac groups (35%, p = 0.042), demonstrating for the first time that the combination with curcumin, rather than iron supplementation alone, results in increased serum BDNF. The addition of curcumin to iron supplementation may therefore provide a novel approach to further enhance the benefits associated with increased BDNF levels.

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A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2021-000680 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000680

Author(s):

Kathy Weisel ◽

Nicola Scott ◽

Scott Berger ◽

Susanne Wang ◽

Kurt Brown ◽

...

Keyword(s):

Quality Of Life ◽

Ulcerative Colitis ◽

Disease Activity ◽

Controlled Study ◽

Experimental Medicine ◽

Open Label ◽

Double Blind ◽

Treatment Groups ◽

To Receive

ObjectiveTumour necrosis factor signalling via the receptor-interacting protein kinase 1 (RIPK1) pathway regulates colonic inflammation suggesting that RIPK1 inhibition may be a potential therapeutic target in ulcerative colitis (UC). This phase IIa, randomised, double-blind experimental medicine study investigated the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of the RIPK1 inhibitor GSK2982772 in patients with active UC.DesignIn part A, prior to a protocol amendment, one patient was randomised to receive GSK2982772 60 mg twice daily for 42 days. After the amendment, patients were randomised 2:1 to receive GSK2982772 60 mg or placebo three times daily for 42 days. In part B, all patients switched to open-label GSK2982772 60 mg three times daily for 42 days. Safety, PK, PD biomarkers, histological disease activity, clinical efficacy and quality of life were assessed at days 43 and 85.ResultsThirty-six patients were randomised (n=12, placebo/open-label GSK2982772; n=24, GSK2982772/open-label GSK2982772). Most adverse events were mild, with headache reported the most frequently across groups (placebo/open-label GSK2982772, n=2 (17%); GSK2982772/open-label GSK2982772, n=8 (33%)). GSK2982772 was well distributed into colonic tissue, with generally higher concentrations in colonic biopsy samples versus plasma. No apparent differences between treatment groups were observed for PD, histological disease activity, clinical disease activity or quality-of-life measures. At screening, all patients had Mayo endoscopic scores of 2 or 3. At day 43, no patients in the placebo/open-label GSK2982772 group achieved Mayo endoscopic scores of 0 or 1 vs 3/24 (13%) for GSK2982772/open-label GSK2982772. At day 85, 1/9 (11%) achieved scores of 0 or one for placebo/open-label GSK2982772 vs 3/22 (14%) for GSK2982772/open-label GSK2982772.ConclusionGSK2982772 was generally well tolerated, with no treatment-related safety concerns identified. However, no significant differences in efficacy were observed between treatment groups, suggesting that GSK2982772 as monotherapy is not a promising treatment for patients with active UC.Trial registration numberNCT02903966.

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Design of the Tocilizumab in Giant Cell Arteritis Trial

International Journal of Rheumatology ◽

10.1155/2013/912562 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 62

Author(s):

Sebastian H. Unizony ◽

Bhaskar Dasgupta ◽

Elena Fisheleva ◽

Lucy Rowell ◽

Georg Schett ◽

...

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Treatment Phase ◽

Controlled Study ◽

Sustained Remission ◽

Open Label ◽

Double Blind ◽

Open Label Extension ◽

Group A ◽

Group B

Overview. The GiACTA trial is a multicenter, randomized, double-blind, and placebo-controlled study designed to test the ability of tocilizumab (TCZ), an interleukin (IL)-6 receptor antagonist, to maintain disease remission in patients with giant cell arteritis (GCA).Design. Approximately 100 centers will enroll 250 patients with active disease. The trial consists of a 52-week blinded treatment phase followed by 104 weeks of open-label extension. Patients will be randomized into one of four groups. Group A (TCZ 162 mg weekly plus a 6-month prednisone-taper); group B (TCZ 162 mg every other week plus a 6-month prednisone-taper); group C (placebo plus a 6-month prednisone-taper); and group D (placebo plus a 12-month prednisone taper). We hypothesize that patients assigned to TCZ in addition to a 6-month prednisone course are more likely to achieve the primary efficacy endpoint of sustained remission (SR) at 52 weeks compared with those assigned to a 6-month prednisone course alone, thus potentially minimizing the long-term adverse effects of corticosteroids.Conclusion. GiACTA will test the hypothesis that interference with IL-6 signaling exerts a beneficial effect on patients with GCA. The objective of this paper is to describe the design of the trial and address major issues related to its development.

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Galcanezumab in chronic migraine

Neurology ◽

10.1212/wnl.0000000000006640 ◽

2018 ◽

Vol 91 (24) ◽

pp. e2211-e2221 ◽

Cited By ~ 120

Author(s):

Holland C. Detke ◽

Peter J. Goadsby ◽

Shufang Wang ◽

Deborah I. Friedman ◽

Katherine J. Selzler ◽

...

Keyword(s):

Injection Site ◽

Chronic Migraine ◽

Injection Site Reaction ◽

Treatment Phase ◽

Preventive Treatment ◽

Controlled Study ◽

Open Label ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo

ObjectiveTo evaluate the efficacy and safety of galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, in the preventive treatment of chronic migraine.MethodsA phase 3, randomized, double-blind, placebo-controlled study of LY2951742 in patients with chronic migraine (Evaluation of Galcanezumab in the Prevention of Chronic Migraine [REGAIN]) was a phase 3 study with a 3-month double-blind, placebo-controlled treatment phase and a 9-month open-label extension. Eligible patients 18 to 65 years of age with chronic migraine were randomized 2:1:1 to monthly subcutaneous injections of placebo (n = 558), galcanezumab 120 mg (with a 240-mg loading dose, n = 278), or galcanezumab 240 mg (n = 277). The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days (MHDs) during the 3-month double-blind treatment phase.ResultsMean number of monthly MHDs at baseline was 19.4 for the total sample. Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo −2.7, galcanezumab 120 mg −4.8, galcanezumab 240 mg −4.6) (p < 0.001 for each dose compared to placebo). There were no clinically meaningful differences between galcanezumab doses and placebo on any safety or tolerability outcome except for a higher incidence of treatment-emergent injection-site reaction (p < 0.01), injection-site erythema (p < 0.001), injection-site pruritus (p < 0.01), and sinusitis (p < 0.05) in the galcanezumab 240-mg group relative to placebo.ConclusionsBoth doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs. Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.ClinicalTrials.gov identifierNCT02614261.Classification of evidenceThis interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.

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An Evaluation of Nasal Response following Different Treatment Regimes of Oxymetazoline with Reference to Rebound Congestion

American Journal of Rhinology ◽

10.2500/105065897782537197 ◽

1997 ◽

Vol 11 (2) ◽

pp. 109-116 ◽

Cited By ~ 31

Author(s):

Sara Morris ◽

Ronald Eccles ◽

S. Jawad Martez ◽

Donald K. Riker ◽

Theodore J. Witek

Keyword(s):

Day Treatment ◽

Nasal Congestion ◽

Vehicle Group ◽

Controlled Study ◽

Nasal Airway ◽

Visual Examination ◽

Double Blind ◽

Treatment Groups ◽

Treatment Regimes ◽

Nasal Function

This was a randomized, double-blind vehicle controlled study aimed at investigating the effects on nasal function of 7 days treatment with the topical decongestant oxymetazoline (0.05% w/v). Fifty healthy volunteers took part in the study and these were randomly allocated to three treatment groups (i) daily oxymetazoline (b.i.d. 150 μl per nostril) (ii) intermittent oxymetazoline, with oxymetazoline being substituted for vehicle at the morning doses on days 1, 3, and 7; and (iii) daily vehicle (b.i.d. 150 μl per nostril). The nasal airway was assessed by measurement of nasal airway resistance (NAR) using posterior rhinomanometry, subjective scaling of nasal patency by means of a visual analogue scale (VAS), and clinical visual examination. On days 1, 2, 3, and 7, NAR and VAS measurements were obtained before the morning dose and up to 6 hours after dosing; clinical visual examinations were also performed before dosing on these days. NAR and VAS measurements were also made following withdrawal of treatment on Days 8 and 9. Nonparametric analysis of the results showed that therapeutic tolerance to oxymetazoline did not develop over the 7-day treatment period, and visual examination of the nasal mucosa failed to find significant evidence of rhinitis. Evidence of rebound nasal congestion was found following 3 days of oxymetazoline treatment, with baseline NAR within the daily and intermittent oxymetazoline groups being significantly greater on Day 3 compared to Day 1 (p < 0.05). However, there was a trend toward increasing baseline NAR in the vehicle group over the course of the study, suggesting that the vehicle may have contributed to the rebound congestion. Following the withdrawal of treatments, only the intermittent oxymetazoline group had significantly higher NAR on Days 8 and 9 compared to Day 1 (p < 0.05). Subjective VAS measurements generally followed trends in NAR.

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The PATCH trial: efficacy and safety of 5% lidocaine-medicated plaster for the treatment of patients with trigeminal neuralgia: a study protocol for a multicentric, double-blind, enriched enrolment randomised withdrawal, vehicle-controlled study

BMJ Open ◽

10.1136/bmjopen-2020-045493 ◽

2021 ◽

Vol 11 (8) ◽

pp. e045493

Author(s):

Chunmei Zhao ◽

Niti Shrestha ◽

Hongbing Liu ◽

Ying Shen ◽

Lan Meng ◽

...

Keyword(s):

Side Effects ◽

Trigeminal Neuralgia ◽

Study Protocol ◽

Controlled Trial ◽

Treatment Phase ◽

Treatment Method ◽

Controlled Study ◽

Open Label ◽

Double Blind ◽

Patch Trial

IntroductionTrigeminal neuralgia (TN) is characterised by a sudden, severe, electric shock like paroxysmal pain, which is almost always associated with triggers. Carbamazepine is the first-line medical management of TN. However, side effects are common. Currently, there is no ideal treatment for TN. Since there is a known abnormality of Na+ channels in the trigger zone, 5% lidocaine-medicated plaster (LMP), which can block the Na+ channels on Aδ and C fibres, is an effective treatment method in many chronic pain conditions. A case report has found the benefit of LMP for the treatment of TN without any side effects. Whether LMP is an option for the treatment of TN is worth exploring.Methods and analysisThe PATCH trial is a double-blind, enriched enrolment with randomised withdrawal, vehicle-controlled trial, aiming to explore the effects and safety of LMP in patients with TN. There is a 3-week initial open-label phase, followed by a 4-week double-blind treatment phase for responders. In the double-blind phase, patients will have to withdraw from this PATCH study if they meet one of the following criteria for treatment failure such as: >50% increase in pain intensity or paroxysms, lack of efficacy or side effects. The primary outcome will be the number of treatment failures. Adverse events will also be monitored throughout the study.Ethics and disseminationThis study protocol has been approved by the Institutional Review Board of Beijing Tiantan Hospital (approval number: KY 2020-102-02). The results will be disseminated in international academic meetings and published in peer-reviewed journals.Trial registration numberNCT04570293.

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

SLEEP ◽

10.1093/sleep/zsab072.484 ◽

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<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<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<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

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Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

Genetics in Medicine ◽

10.1038/s41436-021-01287-7 ◽

2021 ◽

Author(s):

Ravi Savarirayan ◽

Louise Tofts ◽

Melita Irving ◽

William R. Wilcox ◽

Carlos A. Bacino ◽

...

Keyword(s):

Growth Velocity ◽

Bone Growth ◽

Growth Factor Receptor ◽

Extension Study ◽

Controlled Study ◽

Open Label ◽

Phase 3 ◽

Double Blind ◽

Pathogenic Variants ◽

Growth Promoting

Abstract Purpose Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

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