Safety and tolerability of pasireotide long-acting release in acromegaly-results from the acromegaly, open-label, multicenter, safety monitoring program for treating patients who have a need to receive medical therapy (ACCESS) study

Maria Fleseriu, Elisha Rusch, Eliza B Geer, ACCESS Study Investigators, Maria Fleseriu, Elisha Rusch, Eliza B Geer, ACCESS Study Investigators

Abstract

Purpose: Pasireotide long-acting release is a somatostatin analog that is indicated for treatment of patients with acromegaly. This analysis documents the safety of pasireotide long-acting release in patients with acromegaly enrolled in the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734).

Methods: ACCESS is an open-label, multicenter, single-arm, expanded-treatment protocol designed to provide patients access to pasireotide long-acting release pending regulatory approval. Patients received pasireotide long-acting release 40 mg administered intramuscularly every 28 days. The primary outcome was the proportion of patients having a treatment-emergent grade ≥3 or serious adverse event. Efficacy data were not collected.

Results: Forty-four adult patients with active acromegaly were enrolled in the study for an average of 37.6 weeks (range, 4-70 weeks). Twenty-five grade ≥3 treatment-emergent adverse events were reported in 11 patients (25.0 %), 3 of whom (27.3 %) experienced grade ≥3 hyperglycemia. In patients treated with pasireotide long-acting release for ≥3 months (n = 42), mean glycated hemoglobin and fasting plasma glucose levels increased significantly from 5.9 % and 100.4 mg/dL at baseline to 6.8 % and 135.9 mg/dL at 3 months, respectively. Ten patients (22.7 %) were treated with pasireotide long-acting release for ≥15 months, after which mean glycated hemoglobin and fasting plasma glucose levels were 6.3 % and 123 mg/dL, respectively. Twenty-one patients (48 %) initiated antidiabetic medication.

Conclusions: Grade ≥3 adverse events (primary outcome) were reported in 25.0 % of acromegaly patients treated with pasireotide long-acting release in a clinical setting. Hyperglycemia-related adverse events were reported in 45.5 % of patients, but were typically manageable, supporting the role of pasireotide long-acting release as a safe treatment option for acromegaly patients.

Keywords: Acromegaly; Expanded access trial; Fasting plasma glucose; Glycated hemoglobin; Hyperglycemia; Pasireotide LAR.

Conflict of interest statement

The authors declare that they have no competing interests. Ethical approval The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and implemented and reported in accordance with the International Conference on Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice. The study protocol and informed consent forms were approved by the institutional review board, independent ethics committee, and/or research ethics board of each study site. All patients provided written informed consent to participate in the trial. Informed consent Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Patient disposition
Fig. 2
Fig. 2
Frequency of patients with ≥1 instance of abnormal glycemic parameters after initiation of pasireotide LAR. a Analysis included 43 patients who had evaluable glycemic levels at baseline. b Normal ranges: FPG, 70–99 mg/dL; insulin, 5–15 µIU/mL; HbA1c, 0–6.4 %. No patients had values below the normal range for HbA1c, FPG, or insulin at baseline
Fig. 3
Fig. 3
Monthly assessments of a FPG and b HbA1c during the course of treatment with pasireotide LAR. Dotted lines represent the upper limit of the normal range (FPG, 99 mg/dL; HbA1c, 6.4 %). Markers represent the mean values, and the area of each marker is proportional to the number of patients assessed at each month. Error bars represent the standard deviation. Not all patients initiated treatment with pasireotide LAR at the same time, and the study had a fixed end point (when pasireotide LAR became commercially available and reimbursable). Accordingly, fewer patients being evaluated at latter visits occurred primarily because of the different treatment initiation times for individual patients. BL baseline

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