Dataset Information

Control of IGF-I levels with titrated dosing of lanreotide Autogel over 48 weeks in patients with acromegaly.

ABSTRACT: An essential criterion for control of acromegaly is normalization of IGF-I levels. Somatostatin analogues act to suppress IGF-I and GH levels.To assess the efficacy and safety of 48 weeks titrated dosing of lanreotide Autogel.Open-label, multicentre, phase III, 48-week trial.Patients with active acromegaly (IGF-I levels > 1.3 times upper limit of age-adjusted normal range) were recruited. Twelve injections of lanreotide Autogel were given at 28-day intervals: during the 16-week fixed-dose phase, patients received 90 mg; in the 32-week dose-titration phase, patients received 60, 90 or 120 mg according to GH and IGF-I levels. Intention-to-treat analysis was performed to determine the proportion of patients with normalized age-adjusted IGF-I levels at study end. Secondary evaluations included GH levels, clinical acromegaly signs and safety.Fifty-seven of 63 patients completed the study. Lanreotide Autogel resulted in normalized age-adjusted IGF-I levels in 27 patients (43%, 95% CI 31-55). Mean GH levels decreased from 6.2 to 1.5 microg/l at study end, with 53 of 62 patients (85%) having GH levels < or = 2.5 microg/l (95% CI 76.7-94.3) and 28 of 62 patients (45%) with levels < 1 microg/l (95% CI 32.8-57.6). Twenty-four (38%) had both normal IGF-I levels and GH levels < or = 2.5 microg/l. Acromegaly symptoms reduced significantly in most patients throughout the study. The most common adverse events were gastrointestinal, as expected for somatostatin analogues.Using IGF-I as primary end-point, 48 weeks lanreotide Autogel treatment, titrated for optimal hormonal control, controlled IGF-I and GH levels effectively, reduced acromegaly symptoms and was well tolerated.

SUBMITTER: Chanson P

PROVIDER: S-EPMC2610402 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Control of IGF-I levels with titrated dosing of lanreotide Autogel over 48 weeks in patients with acromegaly.

Chanson Philippe P Borson-Chazot Françoise F Kuhn Jean-Marc JM Blumberg Joëlle J Maisonobe Pascal P Delemer Brigitte B

Clinical endocrinology 20080131 2

<h4>Background</h4>An essential criterion for control of acromegaly is normalization of IGF-I levels. Somatostatin analogues act to suppress IGF-I and GH levels.<h4>Objective</h4>To assess the efficacy and safety of 48 weeks titrated dosing of lanreotide Autogel.<h4>Design</h4>Open-label, multicentre, phase III, 48-week trial.<h4>Methods</h4>Patients with active acromegaly (IGF-I levels > 1.3 times upper limit of age-adjusted normal range) were recruited. Twelve injections of lanreotide Autogel ...[more]

PMID: 18248639

Similar Datasets

Project description:ContextMethodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation.ObjectiveThe aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas.DesignPRIMARYS was a 48-week, multicenter, open-label, single-arm study.SettingThe study was conducted at specialist endocrine centers.PatientsTreatment-naïve acromegalic patients with GH-secreting macroadenomas participated in the study.InterventionLanreotide Autogel 120 mg was administered sc every 28 days (without dose titration).Outcome measuresThe primary endpoint was the proportion of patients with clinically significant (≥20%) tumor volume reduction (TVR) at week 48/last post-baseline value available using central assessments from three readers. The null hypothesis (H0) for the primary endpoint was that the proportion with TVR was ≤55%. Secondary endpoints included: TVR at other time points, GH and IGF-1, acromegalic symptoms, quality of life (QoL), and safety.ResultsSixty-four of 90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/last post-baseline value available was achieved by 62.9% (95% confidence interval, 52.0, 72.9) of 89 patients in the primary analysis (intention-to-treat population; H0 not rejected) and 71.9-75.3% in sensitivity (n = 89) and secondary analyses (n = 63) (H0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance.ConclusionsPrimary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor volume, GH and IGF-1, and acromegalic symptoms, and improves QoL.

Project description:INTRODUCTION:Although the previous lanreotide autogel/depot syringe had been well received, feedback indicated that improvements could be made to make it more user-friendly. Additionally, the view that patients should have greater involvement in the research and development process is echoed by the International Neuroendocrine Cancer Alliance. A series of studies aimed to develop and validate a new syringe that works better for patients, caregivers and healthcare professionals (HCPs) by involving these groups at key stages in the development and testing process. METHODS:The multicentre, international, human factor studies, consisted of four formative studies and one validation study. The formative studies collected patient, caregiver and HCP feedback on the lanreotide autogel/depot syringe on the market at the time, and on newly designed prototypes. The validation study was conducted to evaluate the final syringe to confirm that it can be used effectively and safely in the intended environment, by the intended user, for the intended purpose. RESULTS:Overall, 213 individuals participated in the studies; 145 contributed to the formative studies and 68 to the validation study. The validated new-generation syringe included several important updates compared with the lanreotide autogel/depot syringe currently on the market, including the flanges, which are now larger and have a better grip; the overcap, which is white, ridged, opaque and bigger; the plunger supports and the thermoformed tray. No participant hurt themselves or others during the validation study (although several misuses were reported), and all participants succeeded in delivering a complete dose and activating the safety system. CONCLUSION:With collaboration, a new syringe was developed to meet the needs of patients, caregivers and HCPs, whilst ensuring lanreotide was delivered effectively and safely. These studies highlight the importance of involving patients, caregivers and HCPs in clinical evaluation studies to develop medical products that address their concerns and meet their needs. FUNDING:Ipsen. Plain language summary available for this article.

Project description:BACKGROUND:Lanreotide autogel is a somatostatin analog (SSA) approved for the treatment of acromegaly in 73 countries worldwide; however, it is not yet approved in China. The aim of this study was to evaluate the efficacy and safety of lanreotide autogel compared with lanreotide 40?mg prolonged release (PR) in Chinese patients with active acromegaly. METHODS:LANTERN was a phase 3, randomized, open-label, non-inferiority study. Patients with active acromegaly who had undergone surgery ?3?months prior, or were unlikely or unable to undergo surgery, were treated with lanreotide autogel 60/90/120?mg (monthly deep subcutaneous injection) or lanreotide 40?mg PR (intramuscular injection every 7, 10, or 14?days) for 32?weeks. Primary endpoint was mean change-from-baseline in age-adjusted insulin-like growth factor-1 (IGF-1) standard deviation scores (SDS) at the end-of-study. Secondary endpoints included: growth hormone (GH) levels ?2.5??g/L or???1.0??g/L, ?20% reduction in tumor volume (TV) and safety. RESULTS:In total, 128 patients were randomized and received study treatment. Lanreotide autogel was non-inferior to lanreotide 40?mg PR: treatment difference (95% CI) for IGF-1 SDS between groups was -?0.32 (-?0.74, 0.11; per protocol population) and?-?0.27 (-?0.63, 0.09; intention-to-treat [ITT] population), respectively. Reductions in IGF-1 (-?6.453 vs -?7.003) and GH levels (-?9.548??g/L vs -?13.182??g/L), and the proportion of patients with ?1 acromegaly symptom (-?20.3% vs -?32.5%) were observed from baseline to end-of-study in lanreotide autogel and lanreotide 40?mg PR groups, respectively. In the lanreotide autogel group, 45.5% (25/55) patients achieved ?20% reduction in TV compared with 50.9% (25/53) in lanreotide 40?mg PR group (ITT). Safety profiles were similar in both treatment groups. CONCLUSIONS:Lanreotide autogel was non-inferior to lanreotide 40?mg PR in Chinese patients with active acromegaly after 32?weeks of treatment. TRIAL REGISTRATION:Retrospectively registered on ClinicalTrials.gov: NCT02493517 (9 July 2015); prospectively registered on chinadrugtrials.org.cn: CTR20140698 (24 October 2014).

Project description:PurposeTo investigate the characteristics of difficult intubation and identify novel efficient predictors in patients with acromegaly.MethodsPatients with either untreated acromegaly or non-functional pituitary adenomas were enrolled. Patients with acromegaly underwent hormone assays, upper airway computed tomography and magnetic resonance imaging examinations and preoperative overnight polysomnography. The modified Mallampati classification, mouth opening, neck circumference, and neck extension were assessed, and the Cormack-Lehane grades and the time of tracheal intubation were recorded.ResultsPatients with acromegaly had a higher incidence of difficult intubation (62.5%). The time of tracheal intubation was prolonged, the neck circumference was enlarged, and the neck extension was confined. In patients with acromegaly and difficult intubation, the insulin-like growth factor 1 levels and apnea/hypoxia index were significantly higher compared to patients without difficult intubation (1115.40?±?253.73 vs. 791.67?±?206.62 ng/ml, P?=?0.020; 22.17?±?23.25 vs. 2.47?±?2.84, P?=?0.026, respectively). The bilateral regression analysis revealed that high levels of insulin-like growth factor 1 were an independent risk factor for developing difficult intubation (p?=?0.042, Exp B?=?1.006). The modified Mallampati classification was positively correlated with apnea/hypoxia index and could be calculated using the following logarithmic equation: MMC?=?0.2982 * ln (AHI)?+?2.1836.ConclusionsIn patients with acromegaly, neck movement is confined, the time of tracheal intubation is prolonged, and the neck circumference is enlarged, and these patients suffer from an increased incidence of difficult intubation (62.5%) during anesthesia induction. The apnea/hypoxia index and insulin-like growth factor 1 levels are both increased in acromegalic patients with difficult intubation, and elevated insulin-like growth factor 1 levels are an independent risk factor of difficult intubation in acromegalic patients.

Dataset Information

Control of IGF-I levels with titrated dosing of lanreotide Autogel over 48 weeks in patients with acromegaly.

Publications

Control of IGF-I levels with titrated dosing of lanreotide Autogel over 48 weeks in patients with acromegaly.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets