Lanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients

• Acromegaly symptoms [ Time Frame: 7 months ] [ Designated as safety issue: No ]
• Quality of life [ Time Frame: 7 months ] [ Designated as safety issue: No ]
• Adverse events, clinical evaluation, vital signs [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
• Glucose tolerance [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
• Standard haematology and biochemistry [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
• Gallbladder ultrasound [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
• Pituitary tumor size [ Time Frame: 7 months ] [ Designated as safety issue: No ]
• ECG [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
• Anti-lanreotide Autogel antibodies, anti-pegvisomant antibodies [ Time Frame: 7 months ] [ Designated as safety issue: No ]
• Lanreotide and pegvisomant serum levels (minimum observed concentrations Cmin) [ Time Frame: 7 months ] [ Designated as safety issue: No ]
• To assess the effect of lanreotide - pegvisomant co-administration on: GH, GH binding protein, acid labile subunit and prolactin levels [ Time Frame: 7 months ] [ Designated as safety issue: No ]

• To assess the effect of lanreotide - pegvisomant co-administration on:
• Acromegaly symptoms
• Quality of life
• Safety based on:
• Adverse events, clinical evaluation, vital signs
• Glucose tolerance
• Standard haematology and biochemistry
• Gallbladder ultrasound
• Pituitary tumor size
• ECG
• Anti-lanreotide Autogel antibodies, anti-pegvisomant antibodies
• Lanreotide and pegvisomant serum levels (minimum observed concentrations Cmin)
• Additional Study Objectives:
• To assess the effect of lanreotide - pegvisomant co-administration on: GH, GH binding protein, acid labile subunit and prolactin levels

The main aim of this study is to assess the efficacy of the co-administration of lanreotide Autogel 120 mg (administered via deep sub-cutaneous injections every 28 days) and pegvisomant (administered at 40 to 120 mg per week via sub-cutaneous injection given once or twice a week) on IGF-1 levels over 28 weeks in acromegalic patients. The primary endpoint will be the percentage of acromegalic patients with normalised (age and sex adjusted) IGF-1 level at the end of the co-treatment period.

• Drug: lanreotide (Autogel formulation)
  120 mg administered via deep subcutaneous injection every 28 days over 28 weeks.
• Drug: Pegvisomant
  Administered at 40 to 120 mg per week via subcutaneous injection once or twice a week over 28 weeks.

Inclusion Criteria:

• The patient must have had documentation supporting the diagnosis of acromegaly, including elevated GH and/or IGF-1 levels
• The patient is treated with pegvisomant, because of IGF-1 level remaining above ULN when treated with somatostatin analogue, on a daily basis for at least 3 months and has normal (age and sex adjusted) IGF-1 level, or IGF-1 level above the upper limit of normal (ULN) after treatment with pegvisomant 30 mg per day, OR the patient is treated with lanreotide Autogel or octreotide LAR for at least 6 months including 3 months at the highest marketed dose and has a serum IGF-1 level above ULN, 28 days after the last injection
• At the end of the run-in period, The patient has a serum IGF-1 level above 1.2 x ULN, or a serum IGF-1 level between ULN and 1.2 x ULN and a serum GH nadir > 1 µg/L (assessed by an OGTT), 28 days after the 3rd injection of lanreotide Autogel 120 mg OR the patient is diabetic and has a serum IGF-1 level above 1.2 ULN, 28 days after the 3rd injection of lanreotide Autogel 120 mg

Exclusion Criteria:

• The patient has undergone pituitary surgery or radiotherapy within 6 months prior to study entry, or it is anticipated that it will be done during the study
• The patient has already been treated with a somatostatin analogue associated with a GH antagonist
• The patient has received dopamine agonist within 6 weeks prior to the study entry
• The patient has abnormal hepatic function at study entry (defined as AST, ALT, GGT, alkaline phosphatase, prothrombin time or total bilirubin above 2 ULN)
• The patient is at risk of pregnancy or is lactating