Oral Octreotide Research Articles

Sustained response to treatment with oral octreotide capsules: Results from the phase 3, randomized, double blind, placebo-controlled optimal study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Impact of imputation method on efficacy results from the phase 3 optimal study of oral octreotide capsules in adult patients with acromegaly

Impact of imputation method on efficacy results from the phase 3 optimal study of oral octreotide capsules in adult patients with acromegaly

Patients receiving a range of doses of prior injectable somatostatin receptor ligands respond to oral octreotide in the treatment of acromegaly: Results from the phase 3 optimal study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Results from the phase 3, randomized, double-blind, placebo-controlled OPTIMAL study of oral octreotide capsules in adult patients with acromegaly

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Analysis of adverse events in adult patients with acromegaly receiving oral octreotide capsules: Results from the phase 3, randomized, double-blind, placebo-controlled optimal study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

MON-LB53 Prior Injectable Somatostatin Receptor Ligand Dose Does Not Predict Oral Octreotide Response In The Treatment Of Acromegaly: Results From The Phase 3 OPTIMAL Study

Background: Injectable somatostatin receptor ligands (SRLs) are the most widely used therapy to control acromegaly. Oral octreotide capsules have been formulated as a potential therapy for this disorder and the efficacy and safety was evaluated in the CHIASMA OPTIMAL prospective phase 3 study in patients with acromegaly who were controlled on injectable SRL treatment of varying doses (Samson et al. ENDO 2020). Methods: Patients with confirmed acromegaly, who had been receiving a stable dose of injectable SRL (≥3 months) up until study entry, were randomized to receive octreotide capsules (40 mg/day) or placebo for 36 weeks. Patients were dose titrated to 60 or 80 mg of oral octreotide or equivalent placebo through week 24 at the investigator’s discretion based on increase of IGF-I levels or worsening of acromegaly signs and symptoms. The primary efficacy endpoint was the proportion of patients who maintained their biochemical response at the end of 36 weeks, defined as average IGF-I ≤1 x ULN between Weeks 34 and 36. An analysis evaluated maintenance of response based on prior dose of injectable SRL. Prior doses of injectable SRL were categorized based on the following classifications: octreotide 10 mg every 4 weeks or lanreotide 60 mg every 4 weeks or 120 mg every 8 weeks were stratified as low; octreotide 20 mg every 4 weeks or lanreotide 90 mg every 4 weeks or 120 mg every 6 weeks were stratified as medium; octreotide 30 mg or 40 mg or lanreotide 120 mg every 4 weeks were stratified as high. Randomization was stratified based on low dose vs med/high dose and efficacy results compared for these strata. The response rates reported for the primary end point are slightly adjusted for stratification differences as prespecified in the statistical analysis plan. Results: Six patients (21.4%) in the octreotide capsule group had received prior treatment with low doses of injectable SRLs while 22 (78.6%) had received prior treatment with medium-high doses of injectable SRLs. Maintenance of response was observed in 16 patients receiving oral octreotide. This included 66.7% of patients (n=4) previously receiving low doses of injected SRLs and 54.5% of patients (n=12) on medium-high injected doses. The treatment effect was consistent irrespective of prior dose of injectable SRL (odds ratio: 5.4 in low dose and 5.9 in medium-high dose). Conclusion: The CHIASMA OPTIMAL study recruited a population receiving predominantly medium-high doses of injectable SRLs and demonstrated maintenance of response in 58% of patients. Oral octreotide treatment effect was consistent irrespective of prior dose of injectable SRL.

OR23-07 Results From the Phase 3, Randomized, Double-Blind, Placebo-Controlled CHIASMA OPTIMAL Study of Oral Octreotide Capsules in Adult Patients with Acromegaly

Many patients taking long-acting somatostatin receptor ligand (SRL) injections as first-line medical therapy in acromegaly report limitations, including ongoing disease symptoms especially near injection cycle end and injection site pain. Oral octreotide capsules may provide an alternative to monthly injections. The phase 3 Octreotide capsules versus Placebo Treatment In MultinationAL centers (OPTIMAL) study assessed efficacy and safety of oral octreotide capsules in patients with acromegaly controlled on injectable SRLs. A multinational, randomized, placebo-controlled study was conducted in 56 adult patients with active acromegaly. Eligible patients were ≥ 18 years of age, had evidence of active disease (IGF-I ≥ 1.3 x ULN ≥3 months after last pituitary surgery), and an average IGF-I ≤ 1.0 x ULN on a stable dose of SRL injections (octreotide or lanreotide). At baseline (1 month following the last injection), patients were randomized to receive octreotide capsule or placebo (28 per group) for 36 weeks, followed by an optional open-label oral octreotide extension. The primary endpoint was proportion of patients maintaining biochemical response, defined as IGF-I ≤ 1.0 x ULN (2-value average at weeks 34 and 36). Secondary endpoints included need for rescue with injectable SRLs, GH response (GH < 2.5 ng/mL), and time to loss of IGF-I response (IGF-I >1.0 and ≥ 1.3x ULN for 2 consecutive visits). Safety and tolerability were assessed. The primary endpoint was met, as 58% of patients receiving octreotide capsules maintained IGF-I response vs 19% receiving placebo (P=0.008). Mean IGF-I levels in patients receiving octreotide capsules were within the reference range at treatment end (0.97 x ULN) vs patients receiving placebo (1.69 x ULN). All secondary endpoints were met. Of patients receiving octreotide capsules, 75% completed 36 weeks without need for rescue therapy. However, 68% of the placebo group required rescue therapy. GH response was maintained at week 36 in a significantly larger proportion of patients receiving octreotide capsules than placebo (78% vs 30%; P=0.001). Median time to loss of IGF-I response was not reached by the end of the study for patients receiving octreotide capsules vs 16 weeks for the placebo group (P <0.0001). Five patients in the placebo group had IGF-I levels in the reference range at the end of 36 weeks. Only 2 (7% of placebo group) did not meet loss of response criteria anytime throughout the study. Octreotide capsules were safe and well tolerated; no new/unexpected safety signals were observed. Most patients (55/56) experienced at least one treatment emergent adverse event; most were mild or moderate in intensity. Overall, 90% of patients who completed the trial on octreotide capsules opted to enter the open label extension phase. These phase 3 data demonstrate octreotide capsules to be potentially safe and effective for the treatment of adults with acromegaly.

MON-297 Withdrawal from Long-Acting Somatostatin Receptor Ligand Injections in Adult Patients with Acromegaly: Results from the Phase 3, Randomized, Double-Blind, Placebo-Controlled CHIASMA OPTIMAL Study

Data on the impact of withdrawal from long-acting somatostatin receptor ligand (SRL) injections on disease activity in patients with acromegaly are limited. The phase 3 Octreotide capsules versus Placebo Treatment In MultinationAL centers (OPTIMAL) study assessed the efficacy and safety of oral octreotide capsules in adult patients with acromegaly responding to injectable SRL therapy. The placebo-controlled arm of this study allowed for assessment of acromegaly biochemical and disease activity in patients after withdrawal from SRL treatment. A multinational, randomized, placebo-controlled study was conducted in 56 adult patients with active acromegaly. Patients were ≥ 18 years of age, had evidence of active disease (defined as IGF-I ≥1.3 x ULN after last pituitary surgery), and an average IGF-I ≤ 1.0 x ULN in response to a stable dose of SRL injection. Patients were randomized, 1 month following their last injection, to octreotide capsule or placebo for 36 weeks, with an option to enroll in an open-label extension. The primary aim was to determine the proportion of patients maintaining biochemical response, defined as IGF-I ≤1.0 x ULN (average of week 34 and 36). The trial met the primary endpoint, with 58% (16/28) of patients receiving octreotide capsules maintaining IGF-I response vs 19% (5/28) receiving placebo (P=0.008). The median time to loss of response (2 criteria evaluated: IGF-I >1.0 and ≥ 1.3 x ULN for 2 consecutive visits) was 16 weeks in the placebo group, while it was not reached in the octreotide capsule group. Of the 5 patients in the placebo group who maintained their biochemical response at 36 weeks, only 2 (7% of placebo group) did not meet loss of response criteria. When IGF-I values for any 2 consecutive visits were analyzed for patients receiving placebo, 93% (26/28) lost response based on IGF-I > 1 x ULN and 79% (22/28) lost response based on IGF-I ≥ 1.3 x ULN. Irrespective of biochemical control of acromegaly, 26/28 patients receiving placebo experienced active disease-related symptoms reported as AEs of special interest (AESIs). Most common AESIs (≥ 5%) included arthralgia/arthritis (60.7%), soft tissue swelling (35.7%), headache (32.1%), hyperhidrosis (25%), carpal tunnel (14.3%), musculoskeletal pain (14.3%), weight increased (7.1%) and tongue disorders (7.1%). The 5 patients receiving placebo with controlled IGF-I at 36 weeks received active medical treatment in the open label extension by decision of their study PIs, as they were deemed to have either lost their response during the study or had continuing active acromegaly symptoms. 93% of patients receiving placebo lost response following withdrawal of injectable SRLs, with a median duration of 16 weeks. All 5 patients receiving placebo who met the primary endpoint criteria at the end of the study were assessed clinically to have active disease and were continued on oral SRL treatment in the open label extension.

MON-314 Analysis of Adverse Events in Adult Patients with Acromegaly Receiving Oral Octreotide Capsules: Results from the Phase 3, Randomized, Double-Blind, Placebo-Controlled CHIASMA OPTIMAL Study

Distinguishing non-specific signs and symptoms of acromegaly from treatment emergent adverse events (TEAEs) in patients treated with somatostatin receptor ligands has proven difficult given limited data from placebo-controlled studies. The phase 3 Octreotide capsules versus Placebo Treatment In MultinationAL centers (OPTIMAL) study provides a novel data set to evaluate the incidence of adverse events from patients randomized to octreotide capsules or placebo. A multinational, randomized, placebo-controlled study was conducted in 56 adult patients with active acromegaly. Eligible patients were ≥18 years of age, had active disease (IGF-I ≥1.3 x ULN after last pituitary surgery), and an average IGF-I ≤1.0 x ULN in response to a stable dose of somatostatin receptor ligand injection. Patients were randomized to octreotide capsule or placebo (28 per group) for 36 weeks, followed by an optional open-label extension for up to 1 year. Safety and tolerability were evaluated based on incidence of AEs, including incidence of new or worsening adverse events of special interest (AESIs). In this study, the safety profile of octreotide capsules was consistent with the known safety profile of injectable octreotide (Melmed et al 2015). No new or unexpected safety signals were detected. Nearly all patients (55/56) experienced a TEAE (28 patients [100.0%] in the octreotide capsule group and 27 patients [96.4%] in the placebo group). Thirty-three patients (58.9%) experienced a TEAE considered to be related to study drug by the blinded PI (64.3% of the octreotide capsule group [18 patients, 40 events] and 53.8% of the placebo group [15 patients, 41 events]). TEAEs with an incidence ≥5% that were more common in the octreotide capsule group vs placebo group included GI disorders, increased blood glucose, sinusitis, osteoarthritis, and cholelithiasis. TEAEs with an incidence ≥5% that were more common in the placebo group vs octreotide capsule group included arthralgia, headache, fatigue, hyperhidrosis, and peripheral swelling. GI disorders were the most common TEAE, reported in 64% of all patients (36/56) and at similar rates between octreotide capsule (68%) and placebo groups (61%). AESIs (defined as new or worsening signs of acromegaly) were observed in 15 patients (53.6%, 34 events total) in the octreotide capsule group and more frequently in 26 patients (92.9%, 82 events total) in the placebo group. In this study, the safety profile of octreotide capsules was consistent with the known safety profile of injectable octreotide. Most patients receiving octreotide capsules or placebo demonstrated TEAEs, although the profile of most common TEAEs varied between groups. TEAEs observed in the placebo group may be indicative of underlying disease activity. Further analysis may elucidate the difference between treatment related AEs and signs/symptoms of active disease in acromegaly.

MON-LB55 Biochemical Control of Most Patients Reverting to Injectable Long-Acting Somatostatin Receptor Ligands Is Achieved After One Dose: Results From the Phase 3, Randomized, Double Blind, Placebo-Controlled Optimal Study

Background: Injectable somatostatin receptor ligands (SRLs) are currently the most widely used medical therapy for acromegaly worldwide. Oral octreotide capsules (OOC) have been formulated as a potential therapy for this disorder and the safety and efficacy were evaluated in the CHIASMA OPTIMAL pivotal study (Samson et al. ENDO 2020). As reported, mean IGF-I levels of the OOC treatment group were maintained within normal range at the end of treatment in all patients. However, some patients may not respond to OOC treatment (25% of OOC group and 68% of placebo groups required rescue, P=0.003). This analysis describes the degree and rapidity with which patients achieve biochemical control (IGF-I ≤1.0 x ULN) when reverted to their prior injectable SRL treatment. Methods: Patients with confirmed acromegaly and receiving a stable dose of injectable SRL (≥3 months) were randomized to OOC (40mg/day; N=28) or placebo (N=28) for 36 weeks. Patients were dose titrated to 60 or 80mg of OOC (or placebo) through week 24 at investigator discretion based on increased IGF-I levels and/or worsening acromegaly signs/symptoms. Patients could be rescued via reversion to prior injectable SRL therapy if they met the predefined withdrawal criteria (i.e., IGF-I ≥1.3 x upper limit of normal [ULN] for 2 consecutive visits on the highest dose, and exacerbation of clinical signs/symptoms) or discontinued treatment early for any other reason. In the study, 7 patients in the OOC group and 19 in the placebo group required rescue. The change in IGF-I from Baseline was compared to the end of the Double-blind Placebo Controlled period. Results: In patients rescued up to week 32 and in whom there were at least 4 weeks of follow up, baseline IGF-I levels (mean of Screening Visit 2 and Baseline) were 0.80 and 0.87 x ULN in the OOC and placebo groups, respectively. In patients receiving rescue therapy, the end of study IGF-I levels (mean of week 34 and 36) were 0.80 and 0.89 x ULN in the OOC and placebo groups, respectively, virtually unchanged. The median time to return to normal baseline IGF-I values following loss of response was 4.0 weeks after discontinuing OOC and 4.0 weeks after discontinuing placebo treatment. Therefore, most patients who required rescue following a short trial of therapy with OOC returned to their baseline values following a single SRL injection. Conclusion: Most treatment failures in the CHIASMA OPTIMAL trial (on either OOC or placebo) rescued with injectable SRL re-established their baseline response levels after a single injectable SRL administration (at pre-study dose). Based on this data, patients may potentially be treated with OOC and for those not responding, either not biochemically controlled or who have adverse effects, they may be able to return to injectable SRLs with immediate IGF-I control after one SRL injection.

MON-LB57 Impact of Imputation Method and Response Cutoffs on Results From the Phase 3 OPTIMAL Study of Oral Octreotide Capsules in Adult Patients With Acromegaly

Objective: The phase 3 CHIASMA OPTIMAL study assessed efficacy and safety of oral octreotide capsules (OOC) in patients with acromegaly controlled on injectable somatostatin receptor ligands (SRLs). Sensitivity analyses were conducted for efficacy endpoints using two methods of imputation (i.e., the process of replacing clinical data with substitution values) to address missing data points due to some subjects reverting back to their prior injectable SRL treatment. Methods: Patients were ≥18 years of age and had evidence of active acromegaly with an average IGF-I ≤ 1.0 x ULN (utilizing the IDS iSYS assay calibrated to WHO recombinant reference standard 02/254). At baseline, patients were randomized to receive OOC or placebo for 36 weeks. The primary endpoint was proportion of patients maintaining biochemical response, defined as IGF-I ≤1.0 x ULN (2-value average at weeks 34 and 36) (Samson et al. ENDO 2020). Per study protocol, patient study discontinuations were considered non-responders regardless of clinical response at the time of discontinuation (non-response imputation). Additional exploratory analyses were performed utilizing the last observation carried forward (LOCF) analysis, as well as a completers analysis of response among the subgroup that completed the entire 36 weeks on study drug. The response rates reported for the primary end point are slightly adjusted for stratification differences as prespecified in the statistical analysis plan. Results: Twenty-eight patients received OOC and 12 failed to maintain biochemical response based on the primary endpoint. Seven of these 12 patients discontinued treatment early - 5 due to treatment failure and 2 due to AEs. The remaining 5 patients completed the 36-week protocol on study drug. Of these 5 patients, 4 had IGF-I values between >1.0 and ≤1.3 x ULN and 1 completed the study with an IGF-I of 1.7 x ULN with no clinical symptoms. 58.2% of patients in the OOC group met the primary endpoint of maintenance of biochemical response at the end of study using the non-response imputation. Using LOCF imputation, 64.3% (18/28) of patients met this endpoint. Of those completing the study (N=21), 76.2% maintained response. Conclusion: CHIASMA OPTIMAL primary endpoint was assessed using the non-response imputation for patients who discontinued treatment early, with a 58.2% response rate. However, when assessing the response rate based on LOCF imputation, or in study completers, similar to other phase 3 studies for acromegaly, the rate was imputed at 64.3% and 76.2%, respectively.

Abstract #864201: Treatment with Oral Octreotide Capsules May Not Influence Glycemic Control in Patients with Acromegaly: Results from the Phase 3 Chiasma Optimal Study

Abstract #864201: Treatment with Oral Octreotide Capsules May Not Influence Glycemic Control in Patients with Acromegaly: Results from the Phase 3 Chiasma Optimal Study

Novel Somatostatin Receptor Ligands Therapies for Acromegaly.

Surgery is considered the treatment of choice in acromegaly, but patients with persistent disease after surgery or in whom surgery cannot be considered require medical therapy. Somatostatin receptor ligands (SRLs) octreotide (OCT), lanreotide, and the more recently approved pasireotide, characterized by a broader receptor ligand binding profile, are considered the mainstay in the medical management of acromegaly. However, in the attempt to offer a more efficacious and better tolerated medical approach, recent research has been aimed to override some limitations related to the use of currently approved drugs and novel SRLs therapies, with potential attractive features, have been proposed. These include both new formulation of older molecules and new molecules. Novel OCT formulations are aimed in particular to improve patients’ compliance and to reduce injection discomfort. They include an investigational ready-to-use subcutaneous depot OCT formulation (CAM2029), delivered via prefilled syringes and oral OCT that uses a “transient permeability enhancer” technology, which allows for OCT oral absorption. Another new delivery system is a long-lasting OCT implant (VP-003), which provide stable doses of OCT throughout a period of several months. Finally, a new SRL DG3173 (somatoprim) seems to be more selective for GH secretion, suggesting possible advantages in the presence of hyperglycemia or diabetes. How much these innovations will actually be beneficial to acromegaly patients in real clinical practice remains to be seen.

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension.

The aim of the present study was to increase the intestinal transport of octreotide (OCT) by targeting the first-pass impact to identify a potential method for decreasing portal vein pressure (PVP) using oral OCT. Thus, the bioavailability of intestinally absorbed OCT was evaluated in normal rats and rats with portal hypertension (PH) that had been administered P-glycoprotein/multidrug resistance-associated protein 2/cytochrome P450 3A4 (P-gp/MRP2/CYP3A4) inhibitors. The mRNA and protein expression levels of P-gp, MRP2 and CYP3A4 were evaluated in normal and PH rats with or without OCT and the inhibitors using RT-PCR, western blot and immunohistochemical analyses. The potential effects of the inhibitor administration on PVP were also examined. The results suggest that P-gp, MRP2 and CYP3A4 play important roles in prohibiting the enteral absorption of OCT, particularly under a PH environment. Moreover, inhibitors of P-gp, MRP2 and CYP3A4 decrease the first-pass effects of OCT and effectively reduce PVP under PH conditions. Therefore, the present results suggest P-gp, MRP2 and CYP3A4 are key factors in the intestinal absorption of OCT. The inhibition of P-gp, MRP2 and CYP3A4 can markedly decrease the first-pass effects of OCT, and their use may facilitate the use of orally administered OCT.

Longitudinal assessment of response to treatment with oral octreotide capsules in patients with acromegaly: post-hoc analysis of a phase 3 trial

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #938: Mpowered: Study Design of a Phase 3 Head-To-Head Trial Evaluating Oral Octreotide Capsules Versus Injectable Somatostatin Analogs in Patients with Acromegaly

Abstract #938: Mpowered: Study Design of a Phase 3 Head-To-Head Trial Evaluating Oral Octreotide Capsules Versus Injectable Somatostatin Analogs in Patients with Acromegaly

New therapeutic agents for acromegaly.

The currently available somatostatin receptor ligands (SRLs) and growth hormone (GH) antagonists are used to control levels of GH and insulin-like growth factor 1 (IGF-1) in patients with acromegaly. However, these therapies are limited by wide variations in efficacy, associated adverse effects and the need for frequent injections. A phase III trial of oral octreotide capsules demonstrated that this treatment can safely sustain suppressed levels of GH and IGF-1 and reduce the severity of symptoms in patients with acromegaly previously controlled by injectable SRL therapy, with the added benefit of no injection-site reactions. Phase I and phase II trials of the pan-selective SRL DG3173, the liquid crystal octreotide depot CAM2029 and an antisense oligonucleotide directed against the GH receptor have shown that these agents can be used to achieve biochemical suppression in acromegaly and have favourable safety profiles. This Review outlines the need for new therapeutic agents for patients with acromegaly, reviews clinical trial data of investigational agents and considers how these therapies might best be integrated into clinical practice.

Somatostatin receptor ligands and resistance to treatment in pituitary adenomas

Somatostatin (SST), an inhibitory polypeptide with two biologically active forms SST14 and SST28, inhibits GH, prolactin (PRL), TSH, and ACTH secretion in the anterior pituitary gland. SST also has an antiproliferative effect inducing cell cycle arrest and apoptosis. Such actions are mediated through five G-protein-coupled somatostatin receptors (SSTR): SSTR1-SSTR5. In GH-secreting adenomas, SSTR2 expression predominates, and somatostatin receptor ligands (SRLs; octreotide and lanreotide) directed to SSTR2 are presently the mainstays of medical therapy. However, about half of patients show incomplete biochemical remission, but the definition of resistance per se remains controversial. We summarize here the determinants of SRL resistance in acromegaly patients, including clinical, imaging features as well as molecular (mutations, SSTR variants, and polymorphisms), and histopathological (granulation pattern, and proteins and receptor expression) predictors. The role of SSTR5 may explain the partial responsiveness to SRLs in patients with adequate SSTR2 density in the cell membrane. In patients with ACTH-secreting pituitary adenomas, i.e. Cushing's disease (CD), SSTR5 is the most abundant receptor expressed and tumors show low SSTR2 density due to hypercortisolism-induced SSTR2 down-regulation. Clinical studies with pasireotide, a multireceptor-targeted SRL with increased SSTR5 activity, lead to approval of pasireotide for treatment of patients with CD. Other SRL delivery modes (oral octreotide), multireceptor-targeted SRL (somatoprim) or chimeric compounds targeting dopamine D2 receptors and SSTR2 (dopastatin), are briefly discussed.

P02-44 Oral octreotide absorption in human subjects: Comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression

P02-44 Oral octreotide absorption in human subjects: Comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression

Oral Octreotide Absorption in Human Subjects: Comparable Pharmacokinetics to Parenteral Octreotide and Effective Growth Hormone Suppression

Oral administration of a novel octreotide formulation enabled its absorption to the systemic circulation, exhibiting blood concentrations comparable to those observed with injected octreotide and maintaining its biological activity. The aim of the study was to determine oral octreotide absorption and effects on pituitary GH secretion compared to sc octreotide injection. Four single-dose studies were conducted in 75 healthy volunteers. Oral doses of 3, 10, or 20 mg octreotide and a single sc injection of 100 μg octreotide were administered. We measured the pharmacokinetic profile of orally administrated octreotide and the effect of octreotide on basal and stimulated GH secretion. Both oral and sc treatments were well tolerated. Oral octreotide absorption to the circulation was apparent within 1 h after dose administration. Escalating oral octreotide doses resulted in dose-dependent increased plasma octreotide concentrations, with an observed rate of plasma decay similar to parenteral administration. Both 20 mg oral octreotide and injection of 0.1 mg sc octreotide resulted in equivalent pharmacokinetic parameters [mean peak plasma concentration, 3.77 ± 0.25 vs. 3.97 ± 0.19 ng/ml; mean area under the curve, 16.2 ± 1.25 vs. 12.1 ± 0.45 h × ng/ml); and median time ≥ 0.5 ng/ml, 7.67 vs. 5.88 h, respectively). A single dose of 20 mg oral octreotide resulted in basal (P < 0.05) and GHRH-stimulated (P < 0.001) mean GH levels suppressed by 49 and 80%, respectively. The results support an oral octreotide alternative to parenteral octreotide treatment for patients with acromegaly.