An Efficacy and Safety Study of Somatuline Depot (Lanreotide) Injection to Treat Carcinoid Syndrome
An Efficacy and Safety Study of Somatuline Depot (Lanreotide) Injection to Treat Carcinoid Syndrome
The purpose of this study was to determine whether monthly deep subcutaneous (s.c.)
 injections of lanreotide Autogel (Somatuline Depot) were effective and safe in controlling
 diarrhoea and flushing by reducing the usage of s.c. short-acting octreotide as a rescue
 medication to control symptoms in subjects with carcinoid syndrome.
This study consisted of a Screening period, conducted up to 4 months before randomisation,
 followed by three phases: a 16-week, double blind (DB), randomised, placebo-controlled phase;
 a 32-week initial open label (IOL) phase; and a long term open label extension (LTOLE) phase.

 The DB phase evaluated lanreotide Autogel versus placebo in subjects with a history of
 carcinoid syndrome (flushing and/or diarrhoea). This was followed by a 32-week IOL phase in
 which all subjects received lanreotide Autogel 120 mg every 4 weeks. Subjects in countries
 where lanreotide Autogel had not been approved for the treatment of carcinoid syndrome, who
 were well-controlled at the end of the 32-week IOL phase and chose to continue to receive
 lanreotide Autogel, were given the option of participating in a LTOLE phase. The LTOLE phase
 of the study was planned to end at least 2 years after the last subject had completed his/her
 participation in the 32-week IOL phase or when marketing approval for the treatment of
 symptoms of carcinoid syndrome had been obtained in the respective countries (whichever
 occurred first) or at any time the study was terminated by the Sponsor. The actual overall
 duration of the study was 6.5 years. During the LTOLE phase all subjects continued to be
 treated with lanreotide Autogel 120 mg every 4 weeks.

 The study planned to enrol approximately 100 adult subjects worldwide. Screening continued
 until 115 subjects were enrolled in the study.
Subjects were eligible for participation in the study if they met the following criteria:

 1. At least 18 years of age at the time of first dosing.

 2. Subjects must have given signed informed consent before any study related activities
 were conducted.

 3. Subjects in the United States of America (USA) must have given written authorisation
 for the release of protected health information in compliance with the Health
 Insurance Portability and Accountability Act (HIPAA) regulations; subjects in other
 countries must have provided appropriate authorisation as needed by regulatory
 authorities in each country.

 4. Subjects must have been willing to receive s.c. octreotide injections as rescue
 medication, as needed to control their symptoms, if any.

 5. If female, the subject must not have been pregnant (confirmed by negative pregnancy
 test) and must have had the following documented via verbally given history:

 -  At least 1 year postmenopausal (natural cessation of menses), or

 -  Surgically sterile (if by tubal ligation, surgery must have been performed more
 than 3 months prior to entry into the study), or

 -  If the subject was of childbearing potential and sexually active, she must have
 been using an acceptable form of contraception (oral, injected, transdermal or
 implanted contraceptives, diaphragm or barrier method with spermicidal and/or
 intrauterine device); local methods such as condoms or sponges/vaginal tablets
 were not acceptable forms of contraception.

 6. Subjects with a histopathologically confirmed diagnosis of carcinoid tumour or, a
 carcinoid tumour of unknown location with liver metastases (documented biopsy), and a
 history of carcinoid syndrome (flushing and/or diarrhoea) who were either naïve to
 treatment with a somatostatin analogue (SSTa) or responsive (according to the opinion
 of the principal investigator) to conventional doses of Sandostatin LAR® Depot (LAR;
 ≤30 mg every 4 weeks) or to daily doses of ≤600 μg of s.c. octreotide.

 7. Confirmation of positive somatostatin receptor (SSTR) status by somatostatin receptor
 scintigraphy (SRS; up to 6 months prior to study entry at the Screening Visit).

 8. Absence of tumour progression documented by two sequential computed tomography (CT)
 scans or two sequential magnetic resonance imaging (MRI) scans (≥3 months apart); the
 last CT or MRI scan must have been performed within 6 months of study entry (Screening
 Visit).

 9. Subjects previously treated with LAR, must have received their last dose of LAR at
 least 4 weeks prior to first dose of study treatment (no later than at the Screening
 Visit).

 10. Be able to communicate and cooperate with the principal investigator and the staff and
 willing to comply with the study instructions.

 Subjects were excluded from entering the study for the following reasons:

 1. History of known allergy or hypersensitivity to investigational drug or any components
 of its formulation, or octreotide.

 2. History of carcinoid syndrome refractory to treatment with conventional doses of SSTa.

 3. Treatment with any other investigational drug within 30 days prior to study entry
 (Screening Visit) and/or at any time during the subject's participation in the study.

 4. Treatment with interferon, chemotherapy and/or radiotherapy (a radiolabelled SSTa)
 and/or tumour debulking <3 months prior to study entry (Screening Visit).

 5. History of hepatic arterial embolisation, hepatic arterial chemoembolisation and/or
 selective internal radiation therapy (selective internal radiation [SIR] therapy
 [SIRT]; e.g. SIR Spheres) <6 months prior to study entry (Screening Visit).

 6. Short bowel syndrome.

 7. Uncontrolled diabetes and/or hypertension.

 8. Severe renal impairment (glomerular filtration rate <30 mL/min/1.73 m2) and/or severe
 liver impairment as evidenced by serum total bilirubin >1.5 mg/dL associated with bile
 duct blockage or with alkaline phosphatase (ALP), aspartate aminotransferase (AST) or
 alanine aminotransferase (ALT) >5.0 upper limit of normal (ULN).

 9. Diagnosis of cardiac disease New York Heart Association (NYHA) functional
 classification >Class I. (Subject has limitation of physical activity. Ordinary
 physical activity causes undue fatigue, palpitation, or dyspnoea).

 10. Life expectancy less than 1 year.

 11. Any malignancies except carcinoid tumour, basocellular carcinoma of the skin, in situ
 carcinoma of the cervix and ≥5 years disease free after curative cancer treatment.

 12. Any serious medical condition that could jeopardise the safety of the subject and/or
 the efficacy assessments of the study.

 13. Subject is being treated with a proton pump inhibitor (PPI) and has been at a stable
 dose (no change in dose or frequency of administration) for less than 4 weeks at study
 entry (Screening Visit).