Serum IGF-1 is a well known and validated marker of acromegaly. IGF-1 assessments were performed at Visit (V) 1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit) and were based on a single serum sample taken in fasting conditions, prior to investigational medicinal product (IMP) administration. Percentage of subjects with a normalised (age and sex adjusted) IGF-1 level at the end of the co-administration period are presented. The last observation carried forward (LOCF) was used to replace missing IGF-1 values.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint.

Serum IGF-1 is a well known and validated marker of acromegaly. IGF-1 assessments were performed at V1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit) and were based on a single serum sample taken in fasting conditions, prior to IMP administration. Percentage of subjects with a normalised (age and sex adjusted) IGF-1 level at the end of the co-administration period, summarised by previous treatment and by final pegvisomant dose are presented. The denominator used to calculate percentages was the number of subjects in each subgroup, comprising previous treatment with pegvisomant, lanreotide Autogel and octreotide long acting repeatable (LAR) and final pegvisomant dose as either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week. The LOCF approach was used to replace missing IGF-1 values.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects within each individual subgroup analysed for each category.

Serum IGF-1 is a well known and validated marker of acromegaly. IGF-1 assessments were performed at V1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit) and were based on a single serum sample taken in fasting conditions, prior to IMP administration. Percentage of subjects with a normalised (age and sex adjusted) IGF-1 level at the end of the co-administration period, summarised by diabetic status are presented. The denominator used to calculate percentages was the number of subjects in each subgroup (diabetic and non diabetic). The LOCF approach was used to replace missing IGF-1 values.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects within each of the two subgroups analysed for each category.

Serum IGF-1 is a well known and validated marker of acromegaly. IGF-1 assessments were performed at V1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit) and were based on a single serum sample taken in fasting conditions, prior to IMP administration. Percentage of subjects with a normalised (age and sex adjusted) IGF-1 level at least once during the co-administration period, summarised by 'while taking the final dose during co-administration' and 'at any time during co-administration' are presented.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint.

Serum IGF-1 is a well known and validated marker of acromegaly. IGF-1 assessments were performed at V1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit) and were based on a single serum sample taken in fasting conditions, prior to IMP administration. The percentage of subjects with a normalised (age and sex adjusted) IGF-1 level is presented. The denominator used to calculate the percentages was the number of ITT population subjects with an assessment at the visit. In addition to the data for each individual visit, the last value available (LVA) data is also presented. None of the ITT population subjects had serum IGF-1 normalised at V3, consistent with the criterion to continue in the study and be treated in the co-administration period.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects with assessments at each specified visit included in analysis.

The change in serum IGF-1 levels, expressed as z-scores calculated using the age and sex specific mean and standard deviation [SD] values from Baseline to V11 and to LVA are presented. A z-score between +/- 2 indicates a normal IGF-1 concentration.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects with assessments at each specified visit included in analysis.

Acromegaly symptoms, including arthralgia, excessive perspiration, fatigue, headache and soft tissue swelling were assessed with scores ranging from 0 (no symptoms) to 8 (severe, incapacitating symptoms). Symptoms were assessed by the subject in paper format before any other procedure planned during the visit. The change in acromegaly symptoms from Baseline to V11 and to LVA are presented.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects with assessments at each specified visit included in analysis.

The ACROQoL is a health-related quality of life (QoL) questionnaire for patients with acromegaly consisting of 22 items measured on a 5-point Likert-type scale that assesses frequency of occurrence (always to never) or degree of agreement (completely agree to completely disagree) with the statements. The ACROQoL consists of questions that evaluate physical (8 items) and psychological aspects related to appearance and personal relations (7 items each). Answers are transformed to a percentage value, where 100 is the maximal (best) and 0 the minimum (worse) score depicting self-perceived quality QoL. An increase in ACROQoL score is associated with an improved QoL. The change in ACROQoL global score, physical and psychological dimension scores and appearance and personal relationships sub-dimension scores from Baseline to V11 and to LVA are presented. Relnship = Relationship; Dim = Dimension.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects with assessments at each specified visit included in analysis.

The correlation between the changes in ACROQoL (expressed as standardised scores and undertaken for global score, physical and psychological dimension scores and appearance and personal relationships sub-dimension scores) over the run-in period (V3 minus V2) and co-administration period (V11 and LVA minus V3) with the corresponding changes in z-score for the IGF-1 level is presented. A decrease in IGF-1 z-score represents an improvement and an increase in ACROQoL score represents an improvement. Spearman's rank correlation (r) values are presented for change from V2 to V3 (Baseline) and from Baseline to V11/LVA for each of the specified ACROQoL categories. Corr = Correlation; Dim = Dimension; Relnship = Relationship.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint.

Serum samples were assessed for GH levels at the same timepoints as the IGF-1 sample at V1 and V2 and during the OGTT (non diabetic subjects only) at V3 and V11 (or at the early withdrawal visit in case of premature discontinuation). Five samples were taken over 2 hours in order to assess GH nadir and confirm the subject's eligibility before entering the co-administration period. For diabetic subjects, the OGTT was replaced by a measurement of GH level on a blood sample taken at the same time as IGF-1 at V3 and V11 (or at the early withdrawal visit). The change in mean serum GH levels from Baseline to V11 and to LVA is presented.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects with assessments at each specified visit included in analysis.

Serum samples were assessed for GH levels at the same timepoints as the IGF-1 sample at V1 and V2 and during the OGTT (non diabetic subjects only) at V3 and V11 (or at the early withdrawal visit in case of premature discontinuation). Five samples were taken over 2 hours in order to assess GH nadir and confirm the subject's eligibility before entering the co-administration period. For diabetic subjects, the OGTT was replaced by a measurement of GH level on a blood sample taken at the same time as IGF-1 at V3 and V11 (or at the early withdrawal visit). The percentage of subjects with serum GH levels ≤ 2.5 ng/mL at Baseline, V11 and LVA is presented.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects with assessments at each specified visit included in analysis.

Serum samples were assessed for GH binding protein levels at V1, V2, V3 and V11 (or at the early withdrawal visit in case of premature discontinuation). The change in mean serum GH binding protein from Baseline to V11 and to LVA is presented.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects with assessments at each specified visit included in analysis.

Serum samples were assessed for acid labile subunit levels at V1, V2, V3 and V11 (or at the early withdrawal visit in case of premature discontinuation). The change in mean acid labile subunit levels from Baseline to V11 and to LVA is presented.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects with assessments at each specified visit included in analysis.

Serum samples were assessed for prolactin levels at V1, V2, V3 and V11 (or at the early withdrawal visit in case of premature discontinuation). The change in mean prolactin levels from Baseline to V11 and to LVA is presented.

The ITT population was defined as all co-administered subjects (treated with at least one dose of each of the two IMPs within the co-administration period) having at least one baseline and at least one post-baseline assessment of the primary efficacy endpoint. Only evaluable subjects with assessments at each specified visit included in analysis.

Weight was recorded at V2, V3 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). The change in mean weight from Baseline to V11 and to LVA are presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Blood pressure (supine after resting for 3 minutes) was recorded at V1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). The change in mean BP (systolic and diastolic) from Baseline to V11 and to LVA are presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Heart rate (supine after resting for 3 minutes) was recorded at V1, V2, V3, V5, V7, V9 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). The change in mean heart rate from Baseline to V11 and to LVA are presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Twelve-lead ECG recordings were performed at V2, V3 and V11. Sinus rhythm, heart rate, PR interval, RR interval, QRS interval and QT interval were measured and heart rate corrected QT interval using the Fridericia method (QTcF) was calculated. The change in ECG mean heart rate from Baseline to V11 and to LVA is presented.

The Safety population was defined as all subjects who received at least one dose of IMP drug during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Twelve-lead ECG recordings were performed at V2, V3 and V11. Sinus rhythm, heart rate, PR interval, RR interval, QRS interval and QT interval were measured and QTcF was calculated. The change in mean ECG parameter for PR interval, QRS interval, QT interval, RR interval and QTcF from Baseline to V11 and to LVA are presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in each individual analysis.

A gallbladder ultrasound was performed at V2, V3, and V11 (or in case of premature study discontinuation, at the early withdrawal visit). Presence of lithiasis and sludge was recorded. Number of subjects who developed or resolved lithiasis and developed or resolved sludge, comparing Baseline to V11 and to LVA are presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant).

Pituitary tumour size was assessed by Magnetic Resonance Imaging at V2, V3 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). The two longest diameters of the pituitary tumour were to be measured. The change in mean pituitary tumour size from Baseline to V11 and to LVA is presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Glucose tolerance was only evaluated in non diabetic subjects. Glucose tolerance was assessed based on measurement of fasting blood glucose and insulin levels taken at V2 and OGTT performed at V3 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). A dose of 75 g oral glucose was given to subjects and blood samples then taken at 30, 60, 90 and 120 minutes after oral glucose to measure glucose, insulin and GH levels, and to evaluate the GH nadir level. The OGTT was performed after the assessment of IGF-1 and all safety laboratory tests, but before IMPs administration at V3. Glucose, insulin and GH levels were assessed before OGTT in fasting conditions and at the same time as IGF-1 assessment. The change in mean blood glucose Cmax (as determined from OGTT) from Baseline to V11 and to LVA is presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Assessed in non diabetic subjects only (n = 38). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Glucose tolerance was only evaluated in non diabetic subjects. Glucose tolerance was assessed based on measurement of fasting blood glucose and insulin levels taken at V2 and OGTT performed at V3 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). A dose of 75 g oral glucose was given to subjects and blood samples then taken at 30, 60, 90 and 120 minutes after oral glucose to measure glucose, insulin and GH levels, and to evaluate the GH nadir level. The OGTT was performed after the assessment of IGF-1 and all safety laboratory tests, but before IMPs administration at V3. Glucose, insulin and GH levels were assessed before OGTT in fasting conditions and at the same time as IGF-1 assessment. The change in mean fasting insulin concentration from Baseline to V11 and to LVA is presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Assessed in non diabetic subjects only (n = 38). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Glucose tolerance was only evaluated in non diabetic subjects. Glucose tolerance was assessed based on measurement of fasting blood glucose and insulin levels taken at V2 and OGTT performed at V3 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). A dose of 75 g oral glucose was given to subjects and blood samples then taken at 30, 60, 90 and 120 minutes after oral glucose to measure glucose, insulin and GH levels, and to evaluate the GH nadir level. The OGTT was performed after the assessment of IGF-1 and all safety laboratory tests, but before IMPs administration at V3. Glucose, insulin and GH levels were assessed before OGTT in fasting conditions and at the same time as IGF-1 assessment. The change in mean fasting glucose concentration from Baseline to V11 and to LVA is presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Assessed in non diabetic subjects only (n = 38). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Glucose tolerance was only evaluated in non diabetic subjects. Glucose tolerance was assessed based on measurement of fasting blood glucose and insulin levels taken at V2 and OGTT performed at V3 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). A dose of 75 g oral glucose was given to subjects and blood samples then taken at 30, 60, 90 and 120 minutes after oral glucose to measure glucose, insulin and GH levels, and to evaluate the GH nadir level. The OGTT was performed after the assessment of IGF-1 and all safety laboratory tests, but before IMPs administration at V3. Glucose, insulin and GH levels were assessed before OGTT in fasting conditions and at the same time as IGF-1 assessment. The change in mean fasting insulin / glucose ratio from Baseline to V11 and to LVA is presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Assessed in non diabetic subjects only (n = 38). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Glycosylated haemoglobin (HbA1C) was measured at V2, V3 and V11 (or in case of premature discontinuation, at the early withdrawal visit). The change in mean HbA1C in diabetic and non diabetic subjects from Baseline to V11 and to LVA are presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in the analysis (56 overall for diabetic + non-diabetic subjects).

Blood samples for clinical laboratory tests were taken at V1, V2, V3 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). During the co-administration period, hepatic toxicity was assessed at each visit (V5 to V10) by measuring alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), prothrombin time and total bilirubin. The change in mean ALT, AST, GGT and alkaline phosphatase from Baseline to V11 and to LVA are presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in each individual analysis.

Blood samples for clinical laboratory tests were taken at V1, V2, V3 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). During the co-administration period, hepatic toxicity was assessed at each visit (V5 to V10) by measuring ALT, AST, alkaline phosphatase, GGT, prothrombin time and total bilirubin. The change in mean total bilirubin from Baseline to V11 and to LVA is presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Blood samples for clinical laboratory tests were taken at V1, V2, V3 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). During the co-administration period, hepatic toxicity was assessed at each visit (V5 to V10) by measuring ALT, AST, alkaline phosphatase, GGT, prothrombin time and total bilirubin. Prothrombin time was expressed as a percentage of the time taken for a control blood sample to clot (designated as 100%) and the mean change from Baseline to V11 and to LVA is presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant). Only evaluable subjects with an assessment at the specified visit were included in the analysis.

Presence of putative antibodies to lanreotide and antibodies to pegvisomant were assessed prior to IMP administration at V2, V4 and V11 (or in case of premature study discontinuation, at the early withdrawal visit). The number of subjects with putative antibodies to lanreotide and to pegvisomant during the co-administration period (Baseline up to V11) is presented.

The Safety population was defined as all subjects who received at least one dose of each IMP during the co-administration period (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant).