Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study

Sheppard, M. C.; Bronstein, Marcello D.; Freda, Pamela U.; Serri, Omar; Marinis, Laura De; Naves, Luciana Ansaneli; Rozhinskaya, Ludmila; Reséndiz, Karina Hermosillo; Ruffin, Matthieu; Chen, YinMiao; Colao, Annamaria

doi:10.1007/s11102-014-0585-6

Cited by 70 publications

(76 citation statements)

References 19 publications

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“…Although there were differences between the current study design and the 2 multinational phase 3 studies, the response rates in the subgroups: SSA uncontrolled, n=20: ~10.0% to 20.0% and others/SSA naïve, n=13: ~15.4% to 30.8% (range based on values at different time points) were consistent with the response rates observed in these 2 phase 3 studies for patients with inadequately controlled acromegaly [16] and patients with treatment-naïve acromegaly [14], respectively. A more pronounced reduction of median percentage change from baseline in standardized IGF-1 was observed in others/SSA-naïve group when compared to SSA-uncontrolled group at month 12, whereas median percentage change from baseline in mean GH was similar in both the groups.…”

Section: Discussionsupporting

confidence: 77%

“…Somatostatin subtype receptors (SSTRs), especially 2 and 5, are found to be prevalent on GH-secreting pituitary adenomas [4]. Octreotide and lanreotide, the first-generation SSAs, which similar to other SSAs except for a higher frequency and degree of hyperglycemia [14][15][16]. Long-acting pasireotide is approved for the treatment of acromegaly by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) [17,18], and in many other countries based on results of these 2 pivotal trials.…”

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confidence: 99%

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Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study

et al. 2017

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ACROMEGALY AND PITUITARY GIGANTISM are rare conditions characterized by chronic hypersecretion of growth hormone (GH) from a pituitary adenoma leading to overproduction of insulin-like growth factor-1 (IGF-1) [1]. Elevated GH and IGF-1 levels lead to metabolic dysfunction and somatic overgrowth, resulting in significant morbidity and mortality. Therefore, the recommended treatment approach is to normalize GH and IGF-1 levels [2]. Abstract.A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levels<2.5μg/L and normalized insulin-like growth factor-1 [IGF-1]) at month 3. Thirty-three patients (acromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GH<2.5μg/L and IGF-1< lower limit of normal). Reductions in the median GH and IGF-1 levels observed at month 3 were maintained up to month 12; the median percent change from baseline to month 12 in GH and IGF-1 levels were −74.71% and −59.33%, respectively. Twenty-nine patients completed the 12-month core phase, 1 withdrew consent, and 3 discontinued treatment due to adverse events (AEs; diabetes mellitus, hyperglycemia, liver function abnormality, n=1 each). Almost all patients (97%; 32/33) experienced AEs; the most common AEs were nasopharyngitis (48.5%), hyperglycemia (42.4%), diabetes mellitus (24.2%), constipation (18.2%), and hypoglycemia (15.2%). Serious AEs were reported in 7 patients with the most common being hyperglycemia (n=2). Long-acting pasireotide demonstrated clinically relevant efficacy and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

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confidence: 77%

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confidence: 99%

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study

et al. 2017

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“…An increase in the dose of sitagliptin and metformin was needed to maintain glycemic control after 24 months of treatment. As was recently reported in the C2305 25-month extension study, metformin was the most commonly used antidiabetic medication for managing pasireotide-induced hyperglycemia (10). Thus, the patient in the current study was able to remain on therapy with sustained control of IGF-1 and clinical symptoms.…”

Section: Discussionsupporting

confidence: 61%

Management of Hyperglycemia in a Patient with Acromegaly Treated with Pasireotide LAR: A Case Study

Gordon¹,

Spiller²

2016

AACE Clinical Case Reports

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Objective: Pasireotide long-acting release (LAR) demonstrated superior efficacy versus octreotide LAR in a phase III study (C2305) in medically naive patients with acromegaly. Adverse events associated with pasireotide LAR were similar to those with octreotide LAR, except for a higher rate of hyperglycemia. The clinical outcomes and management of pasireotide-induced hyperglycemia in a patient from the C2305 study are reported here.Methods: C2305 was a prospective, double-blind study in medically naive patients randomized to receive pasireotide LAR 40 mg or octreotide LAR 20 mg every 28 days. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were measured at baseline and every 3 months thereafter. Glycemic parameters were assessed based on criteria established by the American Diabetes Association.Results: The patient was a 56-year-old woman with acromegaly who had elevated GH and baseline IGF-1 levels 2-fold greater than the upper limit of normal. After 24 months of pasireotide LAR, GH levels were reduced 4-fold from baseline, and IGF-1 was reduced to levels within the reference range. The patient was diagnosed with diabetes at month 3 and initiated treatment with antidiabetic medications, including glimepiride, sitagliptin, and metformin. Glycemic parameters improved at month 12 and remained stable through month 24, except for a slight increase in glycated hemoglobin that prompted antidiabetic dose modification.Conclusion: Pasireotide LAR improved clinical parameters in a patient with persistently elevated GH and IGF-1 levels after surgery. While hyperglycemia was observed during the course of treatment, proactive management with antidiabetic medications quickly led to sustained glycemic control. (AACE Clinical Case Rep. 2016;2:e302-e306) Abbreviations: BID = twice daily; DPP-4 = dipeptidyl peptidase-4; FPG = fasting plasma glucose; GH = growth hormone; GLP-1 = glucagon-like peptide 1; HbA 1c = glycated hemoglobin; IGF-1 = insulin-like growth factor 1; LAR = long-acting release; MRI = magnetic resonance imaging; SC = subcutaneous; SSA = somatostatin analog; sst = somatostatin receptor type

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“…7,8 A phase 3 core study by Sheppard et al found that more patients with normal fasting plasma glucose (FPG)(<100mg/dL) at baseline developed hyperglycemia at their final assessment on pasireotide compared with octreotide (69% vs 39%). 9 Treatment options have been proposed. A phase 1 study by Breitschaft et al, 8 co-administered pasireotide along with an anti-hyperglycemic to healthy volunteers.…”

Section: Discussionmentioning

confidence: 99%

Pasireotide-Induced Hyperglycemia

Kumar¹

2017

MOJCR

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Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study

Cited by 70 publications

References 19 publications

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study

Management of Hyperglycemia in a Patient with Acromegaly Treated with Pasireotide LAR: A Case Study

Pasireotide-Induced Hyperglycemia

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