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Lanreotide Autogel® (lanreotide Depot in the USA) has demonstrated anti-tumor activity and control of the symptoms associated with hormone hypersecretion in patients with neuroendocrine tumors. The objectives of this study were to describe the pharmacokinetics of lanreotide Autogel® administered 4-weekly by deep subcutaneous injections of 60, 90, or 120 mg in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), to quantify the magnitude of inter-patient variability (IPV), and to identify those patient characteristics that impact on pharmacokinetics. Analyses were based on pooled data from clinical trials. A total of 1541 serum concentrations from 290 patients were analyzed simultaneously by the population approach using NONMEM® version 7.2. Covariates evaluated included demographics, renal and hepatic function markers, and disease-related parameters. Serum profiles were described by a one-compartment disposition model in which the absorption process was characterized by two parallel pathways following first- and zero-order kinetics. The estimated apparent volume of distribution was 18.3 L. The estimated apparent total serum clearance for a typical 74 kg patient was 513 L/day, representing a substantial difference in clearance in this population of patients with respect to healthy volunteers that could not be explained by any of the covariates tested. Body weight was the only covariate to show a statistically significant effect on the pharmacokinetic profile, but due to the overlap between the pharmacokinetic profiles of patients with lower or higher body weights the effect of body weight on clearance was not considered clinically relevant. The IPV was low for clearance (27 %) and moderate to high for volume of distribution (150 %) and the absorption constant (61 %). Using two mechanisms of absorption, the pharmacokinetics of lanreotide Autogel® were well-described in patients with GEP-NET. None of the patient characteristics tested were of clinical relevance to potential dose adjustment in clinical practice.

To evaluate the efficacy and safety of lanreotide depot/autogel 120 mg for the control of carcinoid syndrome (CS) symptoms in patients with neuroendocrine tumors (NETs).This was a 16-week, randomized, double-blind, phase 3 trial (Clinicaltrials.gov: NCT00774930). Patients with/without prior somatostatin analog (SSA) use were randomized to lanreotide depot/autogel 120 mg or placebo every 4 weeks, with access to short-acting octreotide as rescue medication. The primary endpoint was the percentage of days in which short-acting octreotide was used, which was assessed from daily diaries using an analysis of covariance including the stratification variables baseline short-acting octreotide use and frequency of diarrhea/flushing. The proportions of patients experiencing treatment success was a supportive analysis. Adverse events were recorded at all visits.A total of 115 patients were enrolled (lanreotide, n = 59; placebo, n = 56). The adjusted mean (95% confidence interval [CI]) percentage of days with rescue octreotide use (primary endpoint) was significantly lower in the lanreotide (33.7%; 95% CI, 25.0%-42.4%) versus the placebo group (48.5%; 95% CI, 39.6%-57.4%), representing an absolute difference of -14.8% (95% CI, -26.8% to -2.8%; P = .017). The odds ratio of full/partial treatment success (≤3 days short-acting octreotide use weeks 12 to 15) was significantly greater with lanreotide than placebo (2.4; 95% CI, 1.1-5.3; P = .036). No new safety concerns were identified, and lanreotide was well tolerated.Lanreotide depot/autogel is effective for the control of CS symptoms in patients (SSA-naïve or experienced) with NETs.AE = adverse event BMI = body mass index CS = carcinoid syndrome ELECT = Evaluating Lanreotide Efficacy and safety as a Carcinoid-syndrome Treatment HRQoL = health-related quality of life LTOLE = long-term open-label extension NET = neuroendocrine tumor OL = open label SSA = somatostatin analog.

In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n=101) or placebo (n=103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n=41; placebo, n=47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs.

Edda Gomez-Panzani,1 Stephen Chang,1 Joaquim Ramis,2 Michelle M Landolfi,1 Bert Bakker11Ipsen Biopharmaceuticals, Inc, Basking Ridge, New Jersey, USA; 2Ipsen Innovation SAS, Pharmacokinetic and Drug Metabolism, Les Ulis, FranceObjective: Lanreotide depot is a long-acting somatostatin receptor ligand injected deep subcutaneously every 4 weeks for the treatment of acromegaly. The aim of the presented studies was to establish whether lanreotide depot, administered to patients with acromegaly at an extended dosing interval of 6 or 8 weeks, is effective in maintaining appropriate serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, with acceptable tolerability.Methods: Two studies were conducted. Study B1 compared lanreotide depot 120 mg (every 4, 6, or 8 weeks) with lanreotide microparticle formulation 30 mg (every 7, 10, or 14 days) in 98 patients who had a GH level of ≤2.5 ng/mL and normalized IGF-1. Study B2 evaluated lanreotide depot 120 mg administered to 64 patients every 8 weeks, after which the dosing interval was adjusted based on GH levels.Results: Mean lanreotide trough serum concentrations at steady state for all dosing intervals were >1.13 ng/mL, shown to achieve a GH level of ≤2.5 ng/mL. In Study B1, following treatment with lanreotide depot given every 6 or 8 weeks, 87.5% and 93.9% of patients, respectively, had normalized GH, whereas 83.3% and 88.5% of patients, respectively, had both normalized GH and IGF-1. In Study B2, 88.9% had normalized GH and 42.9% of patients had normalized GH and IGF-1 following lanreotide depot every 8 weeks. Gastrointestinal disorders, generally mild/moderate in severity, were the most common adverse events.Conclusion: In the studies presented, lanreotide depot 120 mg every 4, 6, or 8 weeks provided effective hormonal control with acceptable safety. An extended dosing interval is a feasible approach for patients adequately controlled with lanreotide depot 60 or 90 mg every 4 weeks.Keywords: growth hormone, insulin-like growth factor-1, pharmacokinetics, pharmacodynamics

Publisher Summary The United States Regulations on Food and Drug Administration is explained in this chapter. In the USA, one of the first attempts to regulate foods was an Act passed in Massachusetts on March 8, 1785. The origin of the Food and Drug Administration (FDA) dates to 1862 when a single chemist, Dr Charles M. Wetherill, was appointed to the US Department of Agriculture. In April 2008, the FDA published a regulatory change ending the need for clinical trials conducted outside the USA to comply with the Declaration of Helsinki. In September 2009, the FDA and the European Medicines Agency (EMA) entered into the agreement known as the EMA-FDA GCP Initiative. The initiative is a confidentiality arrangement in effect through 2010 that allows the sharing of advance drafts of legislation and/or regulatory guidance documents, information related to the authorization and supervision of medicinal products, information, including inspection reports, about GCP inspections for specific products. The FDA also committed to trending data to determine whether there is a difference in data integrity and human subject protection between domestic and foreign clinical trial sites. With respect to expanding its oversight of foreign clinical trials, if the agreement with the EMA proves to be successful, it would indeed leverage this partnership with other regulatory bodies. These recommendations and the FDA's response mean that sponsors can expect more FDA oversight of foreign clinical trial.

Publisher Summary This chapter discusses clinical study conduct and monitoring. Regarding harmonization, good clinical practice (GCP) was established in the USA in 1978 and has evolved constantly ever since. Around the same time GCP was instituted, the European Community increased its focus on harmonization of regulatory requirements for pharmaceuticals. As a result of this harmonization, and to ensure that only good quality, safe, and effective drugs are developed, GCP has most recently been redefined as the International Conference on Harmonization (ICH). The IRB (called the IEC in the EU) is composed of a group of at least five members (and a few alternatives) that ensures that the rights and welfare of humans participating as subjects in a research study are maintained throughout the subjects' participation. Before initiating a clinical study, an investigator meeting is scheduled to ensure that the clinical study sites or institutions that will be responsible for conducting the study have an in-depth understanding of GCPs, the investigational drug, administration and accountability. The CRAs/CSMs should be qualified and experienced individuals responsible for the training of the study site as well as for managing the conduct of the study. According to the FDA, the most common sponsor deficiencies are: inadequate monitoring, failure to secure investigator compliance, failure to submit progress reports. Sponsor deficiencies could also delay the NDA review and approval process, or even result in a non-approval of the NDA.

e15180 Background: CLARINET showed LAN 120 mg significantly increased PFS vs PBO (hazard ratio [HR] for progressive disease [PD]/death 0.47 [95% CI: 0.30, 0.73]) in metastatic intestinal and pancre...

e15181 Background: CLARINET was a large 96-week phase 3 study showing that LAN 120 mg significantly improved progression-free survival vs PBO in patients with intestinal and pancreatic NETs. Here, ...

4104 Background: In CLARINET, progression-free survival (PFS) was significantly prolonged with the somatostatin analog LAN 120 mg vs. placebo in patients with metastatic grade 1 or 2 (Ki-67

e15177 Background: The somatostatin analog LAN 120 mg significantly prolonged progression-free survival (PFS) vs. placebo (PBO) in patients with metastatic grade 1 or 2 (Ki-67

e15182 Background: CLARINET showed antitumor effects with LAN 120 mg in metastatic intestinal/pancreatic NETs. Here, we characterize treatment effects within subgroups defined post hoc by baseline ...

4103 Background: ELECT, a large phase 3 study of the long-acting somatostatin analog (SSA) LAN for symptomatic control of CS in NET patients showed significant improvement over PBO in % days with s...

233 Background: The prognosis for patients with metastatic pNETs is generally poor and current treatment options can be complicated by safety considerations. In CLARINET, progression-free survival (PFS) was significantly prolonged with the somatostatin analog LAN 120 mg vs. placebo (PBO) in patients with metastatic grade 1 or 2 (Ki-67 25%, 95% had stable disease, 77% had received no previous treatment, and 38% had had previous surgery on the tumor. Median PFS in the pNET subgroup was not reached at study end with LAN vs. 12.1 months [95% CI: 9.4, 18.3] with PBO (HR for PD/death: 0.58 [0.32, 1.04]). (Median PFS for LAN at first planned analysis in the open-label extension study was 29.7 months [12.0, 32.4].) The incidence of adverse events (AEs) in the core study was 88% with both LAN and PBO, and the most common AE was diarrhea (LAN, 43%; PBO, 37%). Treatment-related AEs occurred in 55% of the LAN group and 24% of the PBO group. Serious AEs (SAEs) occurred in 29% vs. 43%, respectively; only three of these patients had treatment-related SAEs (two with LAN, one with PBO). Two patients in each group had AEs leading to withdrawal. Conclusions: The evidence in the pNET subgroup suggesting antitumor effects with LAN together with the favorable long-term safety profile support a positive benefit:risk profile for LAN as a first-line treatment for pNETs. Clinical trial information: NCT00353496.

397 Background: Lanreotide Autogel (Depot in US) has been shown in clinical trials to have antitumor effects and control symptoms associated with hormone hypersecretion in GEP NET patients. Objectives: To describe the PK of Lanreotide 60, 90, or 120 mg SC injections every 4 weeks in GEP NET patients, to quantify inter-patient variability (IPV) and to identify PK impacting patient characteristics. Methods: 1,541 serum concentrations were obtained from 290 patients and analysed simultaneously using the population approach with the software NONMEM version 7.2. The covariates evaluated included demographics, renal and hepatic function markers, and disease related information. Results: Serum profiles were described with a one-compartment disposition model and with an absorption process characterized by two parallel absorption pathways following first and zero order kinetics. The estimated apparent volume of distribution was 18.3 L. The estimated apparent total serum clearance for a typical 74 kg patient was 513 L/day. No covariate tested showed a statistically significant effect on the PK profile except body weight, which showed a moderate effect on clearance (clearance increased by 25% as weight increased by 30%). However, when comparing a subject with low weight (51 kg) to a subject with high weight (104 kg), their PK profiles were similar with a great degree of overlapping. Therefore, this weight effect on clearance was not considered clinically relevant. The magnitude of IPV was low for clearance (27%) and moderate for absorption constant (61%). However due to the lack of PK timepoints around the Cmax, a higher IPV was observed for volume of distribution (150%). Mean (SD) derived parameters AUC and Cmaxat steady-state were respectively 239 (64.8) ng.day/mL and 13.9 (7.44) ng/mL, showing moderate IPV in the PK profile. Conclusions: The PK of lanreotide Autogel/Depot was well characterized in GEP NET patients using two mechanisms of absorption. The IPVof the PK of lanreotide was moderate. Among all the patients characteristics tested, none were found clinically relevant to a potential dose adjustment in clinical practice.

Aim: QoL is an important consideration for CS treatment. This analysis evaluated QoL in GEP-NET patients treated for CS in the ELECT study. Methods: ELECT was a 16-week, randomised, double-blind (DB) phase III study (NCT00774930). Patients with GEP-NETs and a history of CS were treated with LAN 120 mg (n = 59) or placebo (n = 56) every 4 weeks. It was followed by 32-week and ≥2-year open-label extensions (OLEs). The primary endpoint was % of days of rescue medication use (SC octreotide) during DB study. Safety evaluations focused on adverse events (AEs). QoL was assessed using the EORTC QLQ-C30 and the EORTC QLQ-GI.NET21. Scores for global health status score (QLQ-C30) and endocrine and gastrointestinal subscales (QLQ-GI.NET21) were secondary endpoints; other scores were exploratory. Results: Mean [95% CI] % of days of rescue medication use was significantly lower with LAN (34% [25, 42%]) than placebo (49% [40, 57%]); difference –15% [–27, –3%], p = 0.02. Treatment-related AEs occurred in 15 (26%) LAN vs. 11 (19%) placebo patients: most common AEs were gastrointestinal. The global health status score (QLQ-C30) remained similar after 12 weeks of DB treatment with LAN and placebo. Treatment differences in endocrine and gastrointestinal subscale scores are shown in the table. For all functional scales of the QLQ-C30, scores remained stable/slightly improved in the LAN group, while there were small deteriorations in the placebo group; however CIs were wide. For the other subscales of the QLQ-GI.NET21, changes in scores were similar in both treatment groups. Conclusions: LAN 120 mg treatment for CS symptoms was not associated with a deterioration in QoL in GEP-NET patients. In fact, despite the relatively short duration of the study, there was evidence of initial improvements in some aspects of QoL. Results of QoL scores in OLE may provides more information. Table: Effect of LAN on QoL secondary endpoints. Values are mean (SD) unless otherwise stated. P-value tested at a significance level of 0.05. A hierarchical testing procedure was applied for secondary endpoints. Data shown are for the transformed scores, which can range from 0 to 100. A higher transformed score for global health status represents a better QoL. A higher transformed score for Endocrine and GI symptoms represents a higher level of symptomatology/problems Lanreotide Autogel Placebo LS mean treatment difference in change from baseline [95% CI] p-value QLQ-C30 Global health status/QoL Baseline 59.89 (20.15) [n = 59] 62.58 (20.28) [n = 55] 4.05 [–2.09, 10.20] 0.1931 Week 12 64.93 (19.37) [n = 48] 61.19 (18.07) [n = 35] 4.05 [–2.09, 10.20] 0.1931 QLQ-GI.NET21 Endocrine symptoms Baseline 25.89 (22.83) [n = 59] 33.54 (23.92) [n = 53] –7.04 [–14.80, 0.73] 0.0750 Week 12 18.06 (20.06) [n = 48] 29.84 (22.51) [n = 35] –7.04 [–14.80, 0.73] 0.0750 QLQ-GI.NET21 Gastrointestinal symptoms Baseline 22.40 (16.95) [n = 59] 24.84 (20.09) [n = 53] –4.68 [–9.63, 0.26] 0.0632 Week 12 17.64 (14.32) [n = 48] 23.62 (15.45) [n = 35] –4.68 [–9.63, 0.26] 0.0632 Disclosure: E. Gomez-Panzani: Ipsen: employee; A.I. Vinik: Ipsen: Research grant, advisory board member; E.M. Wolin: Research grant from Ipsen. Advisory board member for Ipsen, Novartis and Celgene; H. Audry: Received consulting fee (contract statistician) from Ipsen.

Aim: QoL in patients with gastroenteropancreatic-NETs can be affected by the symptom burden, but also treatment efficacy and safety. To better evaluate this, the EORTC developed a NET-specific QoL questionnaire (QLQ-GI.NET21), to be used in combination with its more generic questionnaire, EORTC QLQ-C30. Here, we examine the impact of LAN vs. placebo on QoL from the CLARINET study. Methods: CLARINET was a 96-week randomized double-blind phase III study, in which patients with well/moderately differentiated, non-functioning EP-NETs were treated with LAN 120 mg (n = 101) or placebo (n = 103) deep SC injections every 4 weeks (NCT00353496). The primary endpoint was progression-free survival (PFS). Safety was a key secondary endpoint. QoL (also a secondary endpoint) was assessed at each study visit using the EORTC QLQ-C30 and the EORTC QLQ-GI.NET21. Results: LAN significantly prolonged PFS vs. placebo (stratified log rank, p = 0.0002; hazard ratio 0.47 [95% CI: 0.30, 0.73]). Treatment-related adverse events (AEs) occurred in 50% of patients in the LAN group vs. 28% in the placebo group. Gastrointestinal disorders were the most common AEs (37% vs. 19%). The QLQ-C30 global health status scores and the QLQ-GI.NET21 endocrine and gastrointestinal subscale scores were similar in the two treatment groups at baseline and throughout treatment, though inter-individual variation was high (Table). Results for the other subscale scores of the QLQ-C30 and QLQ-GI.NET21 questionnaires were also similar between LAN and placebo. Conclusions: Overall, patients on LAN 120 mg had a significantly improved PFS and a good safety/tolerability profile that did not compromise patients' QoL vs. placebo. Further analyses are ongoing to evaluate QoL based on patient characteristics and treatment response. Table: Effect of LAN treatment on patients' QoL. Values are mean (SD); LVA, last post-baseline value available Data shown are for the transformed scores, which can range from 0 to 100. A higher transformed score for global health status represents a better QoL. A higher transformed score for Endocrine and GI symptoms represents a higher level of symptomatology/problems Baseline Week 48 Week 96 LVA QLQ-C30 Global health status/QoL LAN 70.2 (19.9) [n = 98] 70.9 (17.3) [n = 71] 66.4 (22.1) [n = 57] 64.5 (23.2) [n = 98] Placebo 73.6 (19.6) [n = 99] 72.0 (14.9) [n = 59] 70.1 (22.2) [n = 34] 67.0 (22.4) [n = 102] QLQ-GI.NET21 Endocrine symptoms LAN 10.9 (15.0) [n = 98] 11.0 (15.5) [n = 71] 11.1 (15.1) [n = 56] 11.7 (14.9) [n = 97] Placebo 12.0 (16.9) [n = 98] 13.2 (18.0 [n = 48] 11.8 (11.3) [n = 34] 13.9 (19.0) [n = 102] QLQ-GI.NET21 Gastrointestinal symptoms LAN 17.1 (16.4) [n = 98] 19.9 (17.6) [n = 71] 15.3 (13.8) [n = 56] 18.2 (16.5) [n = 97] Placebo 18.3 (18.0) [n = 98] 16.0 (14.3) [n = 58] 17.4 (17.3) [n = 34] 19.8 (18.5) [n = 102] Disclosure: P. Ruszniewski: Ipsen: Consultant/advisory role; honoraria; research funding; partner is Ipsen employee. Novartis: honoraria and research funding; M. Caplin: IPSEN: honoraria for consultant/advisory role. NOVARTIS: Consulting fee, Advisory Committees or Review Panels; LEXICON: Consulting fee, Advisory Committees or Review Panel; M. Pavel: Ipsen: Consulting & Speaker role fee. Pfizer, Inc.: Consulting & Speaker role fee. Novartis Pharmaceuticals: Consulting & Speaker role fee, research funding. Lexicon Pharmaceuticals, Inc.: Consulting & Speaker role fee; J. Cwikla: Ipsen: Research Funding; A. Phan: Ipsen: Research Funding; M. Raderer: Speaker fee from: Ipsen, Novartis Pharmaceuticals, Roche Pharmaceuticals, Pfizer, Inc., Bayer, Inc., Celgene; G. Cadiot: Ipsen: Consultant and Speaker fee. Novartis Pharmaceuticals: Consultant and Speaker fee. Keocyt: Consultant and Speaker fee; G. Rindi: Ipsen: Consultant and Speaker fee. Novartis Pharmaceuticals: Consultant and Speaker fee. Pfizer, Inc.: Consultant and Speaker fee. Advanced Accelerator Applications: Consultant fee; A. Langley: Ipsen: Consultant fee; J. Blumberg: Ipsen: employee; E. Gomez-Panzani: Ipsen: employee. All other authors have declared no conflicts of interest.

Objectives: To explore and evaluate Alora placebo patch application and maintenance habits of women in order to identify the factors that influence adhesion success. Methods: This single-center, open-label, placebo, randomized, multiple-application, parallel-group study involved 99 healthy naive users of transdermal patches. Participants applied and wore an Alora placebo patch for ten consecutive applications of approximately 3.5 days each and evaluated adhesion of the patches twice-daily. Three subgroups comprising participants achieving low, moderate or high adhesion success took part in focus groups to discuss their wear habits, practices and attitudes regarding transdermal patches. Results: There was a significant behavioral component involved in patch adhesion. The habits, practices and attitudes of high achievers were clearly different from the other two subgroups. The three most important issues identified to improve adhesion were: mastering the removal of the patch liner, identifying the best site of application, and developing and implementing techniques to maintain patch adhesion. The Alora placebo patch was well tolerated throughout the study. Conclusion: The data showed that there is a learning curve involved in achieving maximal adhesion with a transdermal patch. During the study, a novel patch application method (‘press, fold and slide’) was demonstrated for the participants. This method was very well received by all participants and was more easily executed than the previous method. An adaptation of this method was incorporated into the Alora patient information leaflet, together with several other changes to help improve adhesion success.

268 Background: Somatostatin analogs (SSAs) are the mainstay treatment for carcinoid syndrome. LAN is a long-acting SSA approved for this indication in >50 countries, but not yet in the US. ELECT is a large multinational phase 3 study evaluating rescue therapy use as a novel alternate endpoint for carcinoid symptom control with LAN. Methods: Eligible patients were age ≥ 18 years with histologically-confirmed NET and a history of carcinoid syndrome, and naïve to SSA treatment or responsive to conventional doses of octreotide LAR (≤ 30 mg/4 weeks) or short acting (≤ 600 µg/day SC). Design: a 16-week, randomized (LAN 120 mg [n=59] vs placebo [n=56] every 4 weeks) double-blind phase, followed by a 32-week long-term open label phase on LAN. Patients had access to short acting octreotide as rescue for breakthrough symptoms throughout the study. Primary endpoint: % of days the patient used rescue octreotide during the double-blind phase. The study was designed to have 90% power to detect a treatment difference of 30%. NCT00774930. Results: Among thestudy population, 83 (72%) had symptoms for ≥ 1 year, and51 (44%)had no prior SSA therapy. Mean [95% CI] % of days with rescue medication use was statistically lower with LAN (34% [25, 42%]) vs placebo (49% [40, 57%]), absolute difference –15% [–27, –3%], p=0.02; however, the pre-defined difference was not met. Complete/partial success (≤3 days use) rather than failure (> 3 days use) was more likely with LAN than placebo (OR 2.4 [95% CI 1.1, 5.3]; p=0.04). Treatment emergent AEs: 15 (26%) LAN patients vs 11 (19%) placebo patients; few AEs were serious (2 [3%] vs 5 [9%]) or led to study withdrawal (1 [2%] vs 1 [2%]). Most frequent AEs were GI disorders, 9 (16%) on LAN vs 5 (9%) on placebo. Conclusions: In the ELECT study, LAN significantly reduced need for short acting SSA use with a favorable safety/tolerability profile. This confirms LAN’s positive benefit-risk profile, which is consistent with experience from previous trials and many years of clinical practice in many countries around the world. Clinical trial information: NCT00774930.