In this section, you will find the following information
about Sandostatin® LAR Depot:
- Clinical Effectiveness
- Pharmacokinetics of Sandostatin® LAR Depot
- Clinical Study Design for Sandostatin® LAR Depot Efficacy Determinations
- Conclusions: Efficacy Profile for Sandostatin® LAR Depot in Acromegaly
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is a 28-day long-acting formulation of a proven medication, subcutaneously injected immediate-release Sandostatin® (octreotide acetate) Injection. How can a 28-day, long-acting formulation maintain the clinical effectiveness of a daily-injected formulation?
- Sandostatin® LAR Depot:
- Incorporates octreotide into microspheres of the biodegradable glucose star polymer, D,L-lactic, and glycolic acids copolymer
- Releases octreotide slowly over time
- Maintains all of the clinical and pharmacological characteristics of the immediate-release dosage form (Sandostatin® Injection)
- Has a different pharmacokinetic profile than immediate-release Sandostatin® Injection, allowing for once-monthly injections
Hypothyroidism may occur. Baseline and periodic assessment of thyroid function (TSH, total and/or free T4) is recommended.
In patients with acromegaly, the octreotide concentrations after single intramuscular injections of 10-mg, 20-mg, and 30-mg Sandostatin® LAR Depot are dose proportional1 and offer a smooth PK profile2. Following multiple doses of Sandostatin® LAR Depot given every 4 weeks, steady-state octreotide serum concentrations are achieved after the third injection1. In a phase 2 trial, doses of 20-mg and 30-mg Sandostatin® LAR Depot given every 4 weeks produced steady-state octreotide concentrations of approximately 1.2 ng/mL and 2.1 ng/mL at trough and 1.6 ng/mL and 2.6 ng/mL at peak, respectively1. Peak-to-trough variation in octreotide concentrations ranged from 44% to 68%, compared to the 163% to 209% variation encountered with the daily subcutaneous 3-times-a-day (tid) regimen of immediate-release Sandostatin® Injection1.
Sandostatin® LAR Depot has not been studied in patients with renal or hepatic impairment.
Clinical Study Design for Sandostatin® LAR Depot Efficacy Determinations1
The efficacy of Sandostatin® LAR Depot for treatment of acromegaly was examined in 3 major trials.
- In Studies 1 and 2, 101 patients were enrolled. Treatment was monitored for 27 to 28 months
- In Study 3, 151 patients were enrolled. Treatment was monitored for 12 months
The primary efficacy variable in these trials was GH level. Secondary efficacy variables were IGF-1 level and clinical symptoms/signs of acromegaly. Adverse events and vital signs were also monitored.3,4
Because Sandostatin® LAR Depot is appropriate for patients who have been shown to respond to and tolerate immediate-release Sandostatin® Injection, clinical trials of Sandostatin® LAR Depot were performed in patients who had been receiving immediate-release Sandostatin® Injection for periods ranging from a few weeks to as long as 10 years. The acromegaly studies with Sandostatin® LAR Depot described below were performed in patients who achieved GH levels of <10 ng/mL (and, in most cases <5 ng/mL) while on subcutaneous Sandostatin® Injection. However, some patients enrolled were partial responders to subcutaneous Sandostatin® Injection, i.e., GH levels were reduced by >50% on subcutaneous Sandostatin® Injection compared to the untreated state, although not suppressed to <5 ng/mL1.
All patients responded to Sandostatin® Injection and received long-term treatment with Sandostatin® LAR Depot for up to 27 to 28 months, in which doses of 10 mg, 20 mg, 30 mg, or 40 mg (individually titrated to maintain GH levels at <5 ng/mL) were provided every 28 days1,3.
Study 3 enrolled patients who had received a stable dose of immediate-release Sandostatin® Injection, twice a day (bid) or 3-times-a-day (tid), for at least 4 weeks. Patients were selected for the trial if they achieved a mean 4-hour GH level of <10 ng/mL. Selected patients were then switched to Sandostatin® LAR Depot, which was provided in a dose of 20 mg every 4 weeks for 3 injections. Based on GH levels, subsequent doses were reduced to 10 mg, increased to 30 mg, or maintained at 20 mg for an additional 9 months1,4.
- Of the total 122 patients completing 12 months of treatment1:
- 95% of immediate-release Sandostatin® Injection patients and 97% of Sandostatin® LAR Depot patients had GH levels <5 ng/mL during the screening period and end of treatment
- 69% of immediate-release Sandostatin® Injection patients and 66% of Sandostatin® LAR Depot patients had GH levels <2.5 ng/mL during the screening period and end of treatment
GH Suppression During Long-term Treatment with Immediate-release Sandostatin® Injection and Sandostatin® LAR Depot1
|GH (ng/mL)||Sandostatin® Injection
|Sandostatin® LAR Depot†
|*Average of monthly levels of GH over the course of the trial.
In all of these trials, mean and median GH levels for patients treated with Sandostatin® LAR Depot were equal to or less than those seen when patients were treated with immediate-release Sandostatin® Injection. The investigators concluded that3,4:
- Sandostatin® LAR Depot maintained GH levels as they had been on immediate-release Sandostatin® Injection
- This level of control remained for the entire duration of the trials
IGF-1 Normalization (<500 ng/mL) During Long-term* Treatment With Sandostatin® LAR Depot1
|Sandostatin® LAR* Depot|
|Sandostatin® LAR Depot†
|*During 12 months of treatment
- Powerful control of GH1
- Normalization of IGF-1 in 51% to 67% of patients1
- Consistent drug exposure, dose to dose1
- Proven strength and a more than 20-year heritage of success for combined use of immediate-release Sandostatin® Injection and Sandostatin® LAR Depot for all approved indications *1,5,6
- Convenient dosing for continuing therapy1
Safety data were obtained from one study with the following results:
- The most common adverse events were nausea, headache, back pain, and abdominal pain
- Patient-reported pain at the injection site was noted by about 20% to 25% at a 10-mg dose and about 30% to 50% at the 20-mg and 30-mg doses
*Includes both ongoing and completed trials for all approved indications.
INDICATIONS AND USAGE
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for patients in whom initial treatment with immediate release Sandostatin® (octreotide acetate) Injection has been shown to be effective and tolerated for:
- Long-term maintenance therapy in acromegalic patients who have had inadequate response to surgery and/or radiotherapy or for whom surgery and/or radiotherapy is not an option (the goal of treatment in acromegaly is to reduce GH and IGF-1 levels to normal).
- Long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.
- Long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors.
In patients with carcinoid syndrome and VIPomas, the effect of Sandostatin Injection and Sandostatin LAR Depot on tumor size, rate of growth and development of metastases has not been determined.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions:
- Gallbladder abnormalities may occur: Patients should be monitored periodically.
- Glucose Metabolism: Hypoglycemia or hyperglycemia may occur. Blood glucose levels should be monitored when Sandostatin LAR Depot treatment is initiated or when the dose is altered. Antidiabetic treatment should be adjusted accordingly.
- Thyroid Function: Hypothyroidism may occur. Baseline and periodic assessment of thyroid function (TSH, total and/or free T4) is recommended.
- Cardiac Function: Bradycardia, arrhythmia, conduction abnormalities, and other EKG changes may occur. The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac disease. Use with caution in at-risk patients.
- Nutrition: Octreotide may alter absorption of dietary fats. Monitoring of vitamin B12 levels is recommended during therapy with Sandostatin LAR Depot. Patients on total parenteral nutrition (TPN) and octreotide should have periodic monitoring of zinc levels.
Drug Interactions: The following drugs require monitoring and possible dose adjustment when used with Sandostatin LAR Depot: cyclosporine, insulin, oral hypoglycemic agents, beta-blockers, bromocriptine. Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs. Drugs mainly metabolized by CYP3A4 and which have a low therapeutic index should be used with caution.
Adverse Reactions: The most common adverse reactions occurring in patients receiving Sandostatin LAR Depot are:
- Acromegaly: biliary abnormalities (52%), diarrhea (36-48%), cholelithiasis (13-38%), abdominal pain or discomfort (11-29%), flatulence (26%), influenza-like symptoms (20%), constipation (19%), headache (15%), anemia (15%), hyperglycemia (15%), injection site pain (2-14%), hypertension (13%), dizziness (12%), fatigue (11%), nausea (10%), vomiting (7%), hypothyroidism (2%), hypoglycemia (2%), and goiter (2%).
- Carcinoid Tumors and VIPomas: biliary abnormalities (62%), injection site pain (20-50%), nausea (24-41%), abdominal pain (10-35%), fatigue (8-32%), headache (16-30%), hyperglycemia (27%), back pain (8-27%), constipation or vomiting (15-21%), dizziness (18-20%), sinus bradycardia (19%), pruritus (18%), URTI (10-18%), myalgia (4-18%), flatulence (9-16%), arthropathy (8-15%), rash (15%), generalized pain (4-15%), sinusitis (5-12%), conduction abnormalities (9%), hypoglycemia (4%), and arrhythmia (3%).