Maintenance of response to oral octreotide compared with injectable somatostatin receptor ligands in patients with acromegaly: a phase 3, multicentre, randomised controlled trial

Fleseriu, Maria; Dreval, Alexander; Bondar, Irina; Vagapova, Gulnar; Macut, Djuro; Pokramovich, Yulia; Molitch, Mark E.; Leonova, Nina; Raverot, Gérald; Grineva, Elena; Poteshkin, Yury; Gilgun-Sherki, Yossi; Ludlam, W.H.; Patou, Gary; Haviv, Asi; Gordon, Murray B.; Biermasz, Nienke R.; Melmed, Shlomo; Strasburger, Christian J.

doi:10.1016/s2213-8587(21)00296-5

Cited by 33 publications

(23 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mean IGF-I levels in patients treated with OOC were maintained below the ULN after 36 weeks in the DPC period, and the safety profile of OOC capsules was similar to that observed in prior clinical trials of OOC and to the known profile of injectable octreotide and lanreotide, but with no injection-related AE (12,13). Recently, results of the randomized, openlabel MPOWERED (Maintenance of acromegaly Patients with Octreotide capsules compared With injections-Evaluation of REsponse Durability; NCT02685709) study showed that maintenance of biochemical response to OOC was noninferior to injectable SRLs during the 36week randomized treatment phase (14).…”

Section: Introductionsupporting

confidence: 68%

Durable biochemical response and safety with oral octreotide capsules in acromegaly

Samson

Nachtigall

Fleseriu

et al. 2022

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Objective: To report results from the open-label extension (OLE) of the OPTIMAL trial of oral octreotide capsules (OOC) in adults with acromegaly, evaluating long-term durability of therapeutic response. Design: OLE of a double-blind placebo-controlled (DPC) trial. Methods: Patients completing the 36-week DPC period on study drug (OOC or placebo) or meeting predefined withdrawal criteria were eligible for OLE enrollment at 60 mg/d OOC dose, with the option to titrate to 40 or 80 mg/d. The OLE is ongoing; week 48 results are reported. Results: Forty patients enrolled in the OLE, 20 each having received OOC or placebo, with 14 and 5 patients completing the DPC period as responders, respectively. Ninety percent of patients completing the DPC period on OOC and 70% of those completing on placebo completed 48 weeks of the OLE. Maintenance of response in the OLE (i.e., insulin-like growth factor I [IGF-I] ≤1.0 × upper limit of normal [ULN]), was achieved by 92.6% of patients who responded to OOC during the DPC period. Mean IGF-I levels were maintained between the end of the DPC period (0.91 × ULN; 95% CI, 0.784, 1.045) and week 48 of the OLE (0.90 × ULN; 95% CI, 0.750, 1.044) for those completing the DPC period on OOC. OOC safety was consistent with previous findings, with no increased adverse events (AEs) associated with the higher dose and improved gastrointestinal tolerability observed over time. Conclusions: Patients with acromegaly maintained long-term biochemical response while receiving OOC, with no new AEs observed with prolonged OOC exposure.

show abstract

Section: Introductionsupporting

confidence: 68%

Durable biochemical response and safety with oral octreotide capsules in acromegaly

Samson

Nachtigall

Fleseriu

et al. 2022

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Confirming that Octreotide LAR may also limit the acquaretic effects of Tolvaptan would also have major implications because massive polyuria and nocturia are major limitations to patient compliance to chronic Tolvaptan therapy. Availability of orally active Octreotide (Mycapssa) 92 would also facilitate the finalization of long-term clinical trials and the treatment of ADPKD patients in everyday clinical practice with fixed oral combinations of Octreotide LAR and Tolvaptan.…”

Section: Discussionmentioning

confidence: 99%

Octreotide Lar in Patients with Autosomal Dominant Polycystic Kidney Disease: From Bench to A Novel Perspective of Therapy

Ruggenenti

Perna

Caroli

et al. 2022

MRAJ

View full text Add to dashboard Cite

Polycystins 1 or 2 congenital defects result in impaired Ca2+ inflow through the tubular cell membrane with reduced intracellular Ca2+ concentration and secondary adenylcyclase over-activation with increased intracellular cAMP. This activates chloride-driven fluid secretion and tubular cell proliferation and de-differentiation with cyst formation and growth. Thus, medications, such as the somatostatin analogue Octreotide LAR or the vasopressin antagonist Tolvaptan, that reduce intracellular cAMP, have been tested to inhibit cAMP-mediated chloride secretion and cell proliferation in experimental and human polycystic kidney disease. Seminal studies conducted in the early ‘80s by Franklin Epstein showed that in the shark rectal gland chloride secretion is markedly inhibited by somatostatin in a way suggesting inhibition of adenylcyclase. Evidence that specific receptors for somatostatin, in particular the sst2 subtype, are present in tubular cell membranes suggested that Octreotide LAR binding to its specific renal receptors could exert similar effects in ADPKD cells. In a pilot, cross-over safety study we found that 6-month Octreotide LAR therapy was safe and well tolerated in 12 patients with ADPKD and significantly decreased total kidney volume growth as compared to placebo. Then, the ALADIN and ALADIN II academic, prospective, randomized, placebo-controlled clinical trials found that 3-year Octreotide LAR treatment significantly slowed total kidney and cyst volume growth. In ALADIN treatment slowed chronic decline of directly measured GFR in 79 patients with estimated GFR ≥ 40 ml/min/1.73 m2. In ALADIN II treatment slowed progression to doubling of serum creatinine or ESKD in 100 patients with stage 3b-4 CKD. Treatment was equally safe and well tolerated in both studies. Sub-studies also showed that 3-year Octreotide LAR therapy reduced total liver volume in 27 ADPKD patients with associated polycystic livers and improved left ventricular twisting and untwisting function in 34 ADPKD patients assessed by speckled-tracked echocardiography. Future trials should confirm the long-term benefits of Octreotide LAR in larger populations of ADPKD patients. Moreover, recent studies found that somatostatin analogues and Tolvaptan have additional beneficial effects in experimental polycystic kidney disease. Thus, clinical trials should also explore whether Octreotide LAR and Tolvaptan in combined therapy may have an additional beneficial effect even in human disease.

show abstract

“…The main limitation of the study was the inclusion in the treatment phase only of patients already responsive to oral octreotide, despite demonstrating the efficacy and safety of the oral formulation. Moreover, despite the presence of substantially overlapping side effects between the two formulations, the satisfaction in patients undergoing oral treatment proved to be significantly superior to injective formulation, as measured with AcroTSQ [19]. Oral octreotide may, therefore, represent an interesting therapeutic strategy in patients with a well-controlled disease under injective FG-SRLS, who have difficulty or are reluctant to parenteral administration.…”

Section: Octreotide and Lanreotide: Old Drugs New Perspectivesmentioning

confidence: 98%

Clinical Management of Acromegaly: Therapeutic Frontiers and New Perspectives for Somatostatin Receptor Ligands (SRLs)

et al. 2022

View full text Add to dashboard Cite

Somatostatin receptor ligands (SRLs) represent a true milestone in the medical therapy for acromegaly. The first-generation SRLs (FG-SRLs), octreotide and lanreotide, have demonstrated good efficacy in disease control and tumor shrinkage, and are still considered first-line medical therapies. The development of long-acting release (LAR) formulations has certainly improved the therapeutic tolerability of these drugs, although many patients still experience therapy-related burden. As such, new formulations have recently been developed to improve adherence and therapeutic efficacy and more solutions are on the way. In the case of FG-SRL-resistant disease, pasireotide, the only second generation SRL currently available, demonstrated superiority in disease control and tumor shrinkage compared to FG-SRLs. However, its use in clinical practice is still limited due to concern for impairment in glucose homeostasis. In this review, we discuss the news about the present and future role of SRLs in acromegaly, exploring the therapeutical frontiers of this drug class. Moreover, we provide practical guidance on the use of pasireotide, based on the data in the literature and our clinical experience.

show abstract

Maintenance of response to oral octreotide compared with injectable somatostatin receptor ligands in patients with acromegaly: a phase 3, multicentre, randomised controlled trial

Cited by 33 publications

References 33 publications

Durable biochemical response and safety with oral octreotide capsules in acromegaly

Durable biochemical response and safety with oral octreotide capsules in acromegaly

Octreotide Lar in Patients with Autosomal Dominant Polycystic Kidney Disease: From Bench to A Novel Perspective of Therapy

Clinical Management of Acromegaly: Therapeutic Frontiers and New Perspectives for Somatostatin Receptor Ligands (SRLs)

Contact Info

Product

Resources

About