Clinical Data

Clinical studies

The effect of Somatuline® Depot (lanreotide) Injection on reducing GH and IGF-1 levels and control of symptoms in patients with acromegaly was studied in two long-term, multiple-dose, randomized multicenter studies:

Clinical study 1 was a 1-year study which included a 4-week double-blind placebo-controlled phase, a 16-week-single-blind, fixed-dose phase, and a 32-week open-label dose-titration phase. Patients with active acromegaly based on biochemical tests and medical history entered a 12-week washout period if there was previous treatment with a somatostatin analog or a dopaminergic agonist.16 See Full Prescribing Information for more complete details.

Clinical study 2 was a 48-week, open-label, uncontrolled multicenter study which enrolled patients who had an IGF-1 concentration ≥ 1.3 times the upper limit of the age-adjusted normal range. Patients receiving treatment with a somatostatin analog (other than Somatuline Depot) or a dopaminergic agonist had to attain this IGF-1 concentration after a washout period of up to 3 months.16

See Full Prescribing Information for more complete details.

The following publications offer key information on Somatuline® Depot (lanreotide) Injection and the use of SSAs.

Efficacy of Somatuline Depot after a single dose, and in long-term use

Melmed et al.
Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide Autogel®. Melmed S, Cook D, Schopohl J, et al. Pituitary. 2010; 13(1):18-28.

Synopsis:
This multicenter, randomized, placebo-controlled trial evaluates the long-term efficacy and safety of Somatuline Depot in the treatment of acromegaly. 108 patients were included, across the United States, Europe, and Hong Kong. Patients were followed for 52 weeks over a course of 13 injections at 28-day intervals. The primary endpoint was the >50% reduction of mean serum GH levels.

Safety and efficacy of Somatuline Depot

Chanson et al.
Control of IGF-I levels with titrated dosing of lanreotide Autogel over 48 weeks in patients with acromegaly. Chanson P, Borson-Chazot F, Kuhn JM, et al. Clin Endocrinol (Oxf). 2008;69(2):299-305.

Synopsis:
An open-label, multicenter, Phase III trial to assess the efficacy and safety of 48 weeks of titrated dosing of lanreotide Autogel in normalizing IGF-1 levels for the control of acromegaly. 63 patients participated in the study conducted in France. Injections were titrated at 60, 90, and 120 mg during consecutive, multi-week phases according to GH and IGF-1 levels. Intention-to-treat analysis was performed to determine the proportion of patients with normalized age-adjusted IGF-1 levels at study end.

Pharmacokinetic profile of Somatuline Depot

Bronstein, et al.
Pharmacokinetic profile of lanreotide Autogel in patients with acromegaly after four deep subcutaneous injections of 60, 90 or 120 mg every 28 days. Clin Endocrinol (Oxf). 2005;63:514-519.

Synopsis:
This phase II, randomized, double-blind study assessed lanreotide minimum concentration, maximum concentration, and area under the concentration curve during a dosing interval after a single dose and at steady state in 18 patients, six of whom were randomized to dosages of 60, 90, and 120 mg every 28 days. PK profile, safety and efficacy were assessed after one and four administrations.

Role of SSAs in acromegaly treatment

AACE Acromegaly Guidelines
AACE Acromegaly Guidelines Task Force. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Acromegaly. Endocr Pract. 2011;10(3):213-225.

These consensus guidelines evaluate the current state of the diagnosis and treatment of acromegaly. They state that medical therapy with SSAs is indicated as primary treatment for acromegaly patients who cannot be treated with surgery and/or radiotherapy. They also support the use of SSAs as secondary therapy in patients who have undergone pituitary surgery and continue to have high GH and IGF-1 levels.

Indication and Important Safety Information

  • Somatuline® Depot (lanreotide) Injection is a somatostatin analog indicated for the long-term treatment of patients with acromegaly who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy.

CONTRAINDICATIONS

  • None.

WARNINGS & PRECAUTIONS

  • Somatuline Depot may reduce gallbladder motility and lead to gallstone formation; therefore, patients may need to be monitored periodically.
  • Somatuline Depot and other somatostatin analogs can inhibit the secretion of insulin and glucagon. Patients treated with Somatuline Depot may experience hypoglycemia or hyperglycemia.
  • Antidiabetic treatment may need to be adjusted when Somatuline Depot treatment is initiated or when the dose is altered.
  • Slight decreases in thyroid function have been seen during treatment with Somatuline Depot. Thyroid function tests are recommended where clinically indicated.
  • The most common cardiac adverse reactions observed in patients in 3 pooled cardiac studies were sinus bradycardia (5.5%), bradycardia (2.8%), and hypertension (5.6%).
    • In patients without underlying cardiac disease, Somatuline Depot may lead to a decrease in heart rate without necessarily reaching the threshold of bradycardia.
    • In patients suffering from cardiac disorders prior to Somatuline Depot treatment, sinus bradycardia may occur. Care should be taken when initiating Somatuline Depot treatment in patients with bradycardia.
  • The pharmacological gastrointestinal effects of Somatuline Depot may reduce the intestinal absorption of concomitant drugs.
  • Somatuline Depot may decrease the relative bioavailability of cyclosporine. Cyclosporine dose may need to be adjusted to maintain levels.

SPECIAL POPULATIONS

  • Patients with moderate and severe renal impairment or moderate and severe hepatic impairment should begin treatment with Somatuline Depot 60 mg. Caution should be exercised when considering these patients for an extended dosing interval of Somatuline Depot 120 mg every 6 or 8 weeks.
  • There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, Somatuline Depot should be used during pregnancy only if the potential benefit justifies potential risk to the fetus.
  • A decision should be made whether to discontinue nursing or discontinue Somatuline Depot taking into account the importance of the drug to the mother.
  • Patients receiving beta-blockers, calcium channel blockers, or other drugs that affect heart rate may need dose adjustments to those drugs. Somatuline Depot may reduce the intestinal absorption of coadministered drugs. Caution should be used.

ADVERSE EVENTS

  • In pooled studies (N = 416), the most common adverse reactions (incidence > 5%) were diarrhea (37%), cholelithiasis (20%), abdominal pain (19%), nausea (11%), injection–site reaction (9%), constipation (8%), flatulence (7%), headaches (7%), arthralgia (7%),vomiting (7%), and loose stools (6%).
  • Gastrointestinal adverse reactions were mild to moderate and typically resolved within 8 to 10 weeks.
    • 1% of patients in the pooled studies with Somatuline Depot discontinued treatment due to gastrointestinal adverse events.
  • Occasional cases of pancreatitis have been reported.
  • Injection-site pain (4.1%) and injection-site mass (1.7%) were the most frequently reported local adverse reactions.
  • Local side effects were more common at the start of treatment and less common as treatment continued.
    • Injection–site reactions were usually mild to moderate but did lead to withdrawal from clinical studies in two patients.
For Full Prescribing Information, click here.