Eli Lilly and Company

About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.

The efficacy and safety of tadalafil: an update

Abstract: OBJECTIVE To provide an update on the efficacy and safety of tadalafil, a phosphodiesterase-5 inhibitor, in the treatment of erectile dysfunction (ED). PATIENTS AND METHODS In all, 2102 men (mean age 56 years) with mild-to-severe ED of various causes were randomized to placebo or tadalafil, taken as needed with no food restrictions, at fixed ‘on-demand’ doses of 10 or 20 mg in 11 randomized, double-blind, placebo-controlled trials lasting 12 weeks. The three co-primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function (IIEF) and the proportion of ‘yes’ responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). Additional efficacy instruments included a Global Assessment Question (GAQ). RESULTS Compared with placebo, tadalafil gave significantly better outcomes. Patients receiving either dose of tadalafil had a significant mean improvement of 6.5 and 8.6, respectively, in the IIEF erectile function domain score from baseline (P < 0.001 vs placebo). At both doses the mean success rate for intercourse attempts (SEP-Q3) was 58% and 68%, respectively, compared with 31% in the placebo group (P < 0.001), and 71% and 84% reported improved erections at the endpoint (GAQ), vs 33% on placebo (P < 0.001). Tadalafil was effective up to 36 h after dosing and was effective regardless of disease severity and causes, and in patients of all ages. The most frequent adverse events were headache, dyspepsia, back pain and myalgia. CONCLUSION Tadalafil was an effective and well-tolerated treatment for ED.

Pergolide versus levodopa monotherapy in early Parkinson's disease patients: The PELMOPET study

Abstract: Dopamine agonists are used as initial treatment in patients with Parkinson's disease (PD) to reduce incidence and severity of motor complications. This paradigm is based on long-term studies, allowing "rescue" therapy with levodopa. The present strict monotherapy study (PELMOPET, the acronym for the pergolide-versus-L-dopa-monotherapy-and-positron-emission-tomography trial) evaluated the efficacy and safety of pergolide versus levodopa without levodopa "rescue" medication. This multicenter, double-blind, randomized, 3-year trial compared pergolide monotherapy (n=148) with levodopa monotherapy (n=146) in dopamine-naive patients with early PD (Hoehn and Yahr stage 1-2.5). Primary efficacy measures were clinical efficacy, severity and time to onset of motor complications, and disease progression. During the 3 years, severity of motor complications was significantly lower and time to onset of dyskinesia was significantly delayed in the group receiving pergolide (3.23 mg/day) compared with those receiving levodopa (504 mg/day). However, time to onset of motor complications was not longer in patients receiving pergolide after 3 years. Symptomatic relief (assessed by Unified Parkinson's Disease Rating Scale [UPDRS], UPDRS II, and III, Clinical Global Impressions [CGI] severity, and CGI and Patient Global Impressions [PGI] improvement) was significantly greater in patients receiving levodopa. Adverse events led to discontinuation of therapy in 17.6% of pergolide patients and 9.6% of levodopa patients. This is the first study comparing strict monotherapy with a dopamine agonist versus levodopa in previously untreated early PD. In principle, both levodopa and a dopamine agonist such as pergolide seem to be suitable options as initial PD therapy. The choice remains with the treating physician based on the different efficacy and adverse event profiles.

Plasma ghrelin concentration and energy balance: overfeeding and negative energy balance studies in twins.

Abstract: Central (intracerebral ventral) and peripheral (subcutaneous and intraperitoneal) administration of ghrelin causes obesity in rodents by increasing food intake and decreasing fat oxidation. Recent studies in humans have shown that plasma ghrelin concentration was inversely related to body fat and was lower in Pima Indians, a population susceptible to obesity. Whether ghrelin plays a role in the etiology of obesity in humans is unknown. We, therefore, measured plasma ghrelin concentration before and after two interventions in monozygotic twins previously studied at Laval University, Quebec City. Twelve pairs of monozygotic twins were overfed by 84,000 kcal over a 100-day period, whereas another seven pairs of monozygotic twins were submitted to a 53,000 kcal negative energy balance induced by exercise over a 93-day period. At baseline, for all the subjects, plasma ghrelin concentration was negatively correlated with body mass and body fatness (r varying from 0.36 to 0.45). The intraclass coefficient for the twin resemblance (r(I) = 0.75; p = 0.006) indicated that plasma ghrelin concentration is a familial trait. In response to the 100-day intervention, plasma ghrelin exhibited a non-significant decrease of 61 +/- 30 fmol/l (p = 0.18) with overfeeding and a non-significant increase of 58 +/- 34 fmol/l (p = 0.17) with negative energy balance. However, there was no relationship between baseline plasma ghrelin concentration and the magnitude of body weight change in both interventions. These first experimental data under "clamped energy balance conditions" do not provide evidence that plasma ghrelin is involved in the etiology of human obesity. However, studies in free-living individuals are needed to clarify this question.

Efficacy and safety of subcutaneous tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus erythematosus: results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study

Abstract: Objectives To evaluate the efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that neutralises membrane and soluble B-cell activating factor (BAFF). Methods This randomised, placebo-controlled study enrolled 1124 patients with moderate-to-severe systemic lupus erythematosus (SLE) (Safety of Estrogens in Lupus Erythematosus National Assessment- SLE Disease Activity Index ≥6 at baseline). Patients received standard of care plus subcutaneous study drug, starting with a loading dose (240 mg) at week 0 and followed by 120 mg every 2 weeks (120 Q2W), 120 mg every 4 weeks (120 Q4W) or placebo. Primary endpoint was proportion achieving SLE Responder Index 5 (SRI-5) improvement at week 52. Results Clinical characteristics were balanced across groups. The primary endpoint was met with 120 Q2W (38.4% vs 27.7%, placebo; p=0.002), but not with the less frequent 120 Q4W regimen (34.8%, p=0.051). Although key secondary endpoints (time to severe flare, corticosteroid sparing and fatigue) were not met, patients treated with tabalumab had greater SRI-5 response rates in a serologically active subset and improvements in more stringent SRI cut-offs, SELENA-SLEDAI, Physician9s Global Assessment, anti-double-stranded DNA antibodies, complement, total B cells and immunoglobulins. The incidences of deaths, serious adverse events (AEs), and treatment-emergent AEs were similar in the 120 Q2W, 120 Q4W and placebo groups, but depression and suicidal ideation, albeit rare events, were more commonly reported with tabalumab. Conclusion SRI-5 was met with 120 Q2W and although key secondary endpoints were not met, numerous other secondary endpoints significantly improved in addition to pharmacodynamic evidence of BAFF pathway blockade. The safety profile for tabalumab was similar to placebo, except for depression and suicidality, which were uncommon. Trial registration number NCT01205438.