Trial Outcomes & Findings for Lanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients (NCT NCT00383708)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

125 participants

Primary outcome timeframe

V3 (Week 12; Baseline) up to V11 (Week 44)

Results posted on

2022-09-27

Participant Flow

The study was a multicentre, open, single arm, sequential study where subjects were recruited to 25 study centres across 10 European countries. Subjects were enrolled to the study from 02 October 2006 (first subject enrolled) until 27 October 2008 (last subject completed).

A total of 125 patients were screened. Subjects were assigned to treatment if they met all inclusion and none of the exclusion criteria. 92 subjects received treatment during the run-in period and 57 subjects received treatment during the co-administration period.

Participant milestones

Participant milestones
Measure	All Subjects Subjects confirmed as eligible for the study were entered into a run-in period of 16 weeks during which they received one deep subcutaneous (s.c.) injection of lanreotide Autogel 120 mg every 28 days. If after completion of the run-in period, subjects met the eligibility criteria for levels of serum IGF-1 (and serum growth hormone \[GH\] nadir), they were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg. Pegvisomant was administered once or twice a week via s.c. injection and the dose of could be adapted every 8 weeks based on insulin-like growth factor 1 (IGF-1) levels, following a starting dose of 60 mg once a week (dose could vary from 40 to 120 mg per week and maximum permitted dose was 60 mg twice a week).
Enrolment Through Start Treatment STARTED	125
Enrolment Through Start Treatment COMPLETED	92
Enrolment Through Start Treatment NOT COMPLETED	33
Run-in Period STARTED	92
Run-in Period COMPLETED	85
Run-in Period NOT COMPLETED	7
Co-administration Period STARTED	57
Co-administration Period COMPLETED	52
Co-administration Period NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	All Subjects Subjects confirmed as eligible for the study were entered into a run-in period of 16 weeks during which they received one deep subcutaneous (s.c.) injection of lanreotide Autogel 120 mg every 28 days. If after completion of the run-in period, subjects met the eligibility criteria for levels of serum IGF-1 (and serum growth hormone \[GH\] nadir), they were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg. Pegvisomant was administered once or twice a week via s.c. injection and the dose of could be adapted every 8 weeks based on insulin-like growth factor 1 (IGF-1) levels, following a starting dose of 60 mg once a week (dose could vary from 40 to 120 mg per week and maximum permitted dose was 60 mg twice a week).
Enrolment Through Start Treatment Withdrawal by Subject	1
Enrolment Through Start Treatment Did not meet entry criteria	32
Run-in Period Protocol Violation	4
Run-in Period Adverse Event	2
Run-in Period Claustrophobia	1
Co-administration Period Adverse Event	5

Baseline Characteristics

Lanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Age, Continuous	51.6 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period	57.9 percentage of subjects

PRIMARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Percentage of Subjects With Acromegaly 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 Dose of Pegvisomant Previous Treatment: Pegvisomant	46.2 percentage of subjects
Percentage of Subjects With Acromegaly 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 Dose of Pegvisomant Previous Treatment: Lanreotide Autogel	54.2 percentage of subjects
Percentage of Subjects With Acromegaly 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 Dose of Pegvisomant Previous Treatment: Octreotide LAR	70.0 percentage of subjects
Percentage of Subjects With Acromegaly 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 Dose of Pegvisomant Final Dose Pegvisomant: 40 mg/week	76.9 percentage of subjects
Percentage of Subjects With Acromegaly 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 Dose of Pegvisomant Final Dose Pegvisomant: 60 mg/week	61.5 percentage of subjects
Percentage of Subjects With Acromegaly 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 Dose of Pegvisomant Final Dose Pegvisomant: 80 mg/week	75.0 percentage of subjects
Percentage of Subjects With Acromegaly 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 Dose of Pegvisomant Final Dose Pegvisomant: 40 mg 2x/week	60.0 percentage of subjects
Percentage of Subjects With Acromegaly 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 Dose of Pegvisomant Final Dose Pegvisomant: 60 mg 2x/week	0 percentage of subjects

PRIMARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period; Summarised by Diabetic Status at Baseline Diabetic Subjects	47.4 percentage of subjects
Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period; Summarised by Diabetic Status at Baseline Non Diabetic Subjects	63.2 percentage of subjects

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Percentage of Subjects With a Normalised (Age and Sex Adjusted) IGF-1 Level at Any Time During the Co-administration Period While Taking Final Dose During Co-administration	66.7 percentage of subjects
Percentage of Subjects With a Normalised (Age and Sex Adjusted) IGF-1 Level at Any Time During the Co-administration Period At Any Time During Co-administration	78.9 percentage of subjects

SECONDARY outcome

Timeframe: V1 (Screening) up to V11 (Week 44)

Population: 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 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment V1 (Screening)	17.5 percentage of subjects
Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment V2 (Day 1)	24.5 percentage of subjects
Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment V5 (Week 20)	56.4 percentage of subjects
Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment V7 (Week 28)	48.1 percentage of subjects
Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment V9 (Week 36)	57.7 percentage of subjects
Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment V11 (Week 44)	61.5 percentage of subjects
Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment LVA	57.9 percentage of subjects

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Serum IGF-1 Levels (Expressed as Z-scores) During the Co-administration Period Change at V11	-4.50 z-score Standard Deviation 4.01
Change From Baseline in Serum IGF-1 Levels (Expressed as Z-scores) During the Co-administration Period Change at LVA	-4.25 z-score Standard Deviation 4.00

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=56 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Arthralgia: Change at V11	-0.7 units on a scale Standard Deviation 1.5
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Arthralgia: Change at LVA	-0.6 units on a scale Standard Deviation 1.6
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Excessive Perspiration: Change at V11	-0.4 units on a scale Standard Deviation 1.9
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Excessive Perspiration: Change at LVA	-0.4 units on a scale Standard Deviation 1.8
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Fatigue: Change at V11	-0.2 units on a scale Standard Deviation 1.6
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Fatigue: Change at LVA	-0.2 units on a scale Standard Deviation 1.5
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Headache: Change at V11	-0.4 units on a scale Standard Deviation 1.6
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Headache: Change at LVA	-0.3 units on a scale Standard Deviation 1.6
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Soft Tissue Swelling: Change at V11	-0.6 units on a scale Standard Deviation 1.9
Change From Baseline in Acromegaly Symptoms During the Co-administration Period Soft Tissue Swelling: Change at LVA	-0.6 units on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Global Score: Change at V11	2.4 units on a scale Standard Deviation 9.1
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Global Score: Change at LVA	2.2 units on a scale Standard Deviation 8.8
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Physical Dimensions Score: Change at V11	4.2 units on a scale Standard Deviation 12.0
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Physical Dimensions Score: Change at LVA	3.5 units on a scale Standard Deviation 12.0
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Psychological Dimensions Score: Change at V11	1.3 units on a scale Standard Deviation 10.4
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Psychological Dimensions Score: Change at LVA	1.4 units on a scale Standard Deviation 10.0
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Appearance Sub-Dimension Score: Change at V11	3.8 units on a scale Standard Deviation 13.0
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Appearance Sub-Dimension Score: Change at LVA	3.7 units on a scale Standard Deviation 12.4
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Personal Relnship Sub-Dim Score: Change at V11	-0.1 units on a scale Standard Deviation 12.7
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period Personal Relnship Sub-Dim Score: Change at LVA	-0.9 units on a scale Standard Deviation 12.2

SECONDARY outcome

Timeframe: At V2 (Day 1; Run-in), V3 (Week 12; Baseline) and V11 (Week 44)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V2 to V3 for Global Score	-0.16 correlation value
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V3 to V11/LVA for Global Score	0.09 correlation value
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V2 to V3 for Physical Dim	-0.17 correlation value
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V3 to V11/LVA for Physical Dim	0.14 correlation value
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V2 to V3 for Psychological Dim	-0.1 correlation value
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V3 to V11/LVA for Psychological Dim	0.08 correlation value
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V2 to V3 for Appearance	-0.12 correlation value
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V3 to V11/LVA for Appearance	0.04 correlation value
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V2 to V3 for Personal Relnship	-0.01 correlation value
Correlation Between the Changes in ACROQoL Assessments With the Corresponding Changes in Z-score of IGF-1 Levels Over the Run-in Period and Co-administration Period Corr: Change V3 to V11/LVA; Personal Relnship	0.02 correlation value

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=53 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean Weight From Baseline During the Co-administration Period Change at V11	-0.3 kilograms (kg) Standard Deviation 2.9
Change From Baseline in Mean Weight From Baseline During the Co-administration Period Change at LVA	-0.3 kilograms (kg) Standard Deviation 2.9

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean Supine Systolic and Diastolic Blood Pressure (BP) During the Co-administration Period Supine Systolic BP: Change at V11	-0.4 millimetres mercury (mmHg) Standard Deviation 17.1
Change From Baseline in Mean Supine Systolic and Diastolic Blood Pressure (BP) During the Co-administration Period Supine Systolic BP: Change at LVA	0.2 millimetres mercury (mmHg) Standard Deviation 16.6
Change From Baseline in Mean Supine Systolic and Diastolic Blood Pressure (BP) During the Co-administration Period Supine Diastolic BP: Change at V11	-0.1 millimetres mercury (mmHg) Standard Deviation 11.4
Change From Baseline in Mean Supine Systolic and Diastolic Blood Pressure (BP) During the Co-administration Period Supine Diastolic BP: Change at LVA	-0.3 millimetres mercury (mmHg) Standard Deviation 11.5

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean Supine Heart Rate During the Co-administration Period Change at V11	-3.1 beats per minute (bpm) Standard Deviation 12.6
Change From Baseline in Mean Supine Heart Rate During the Co-administration Period Change at LVA	-2.5 beats per minute (bpm) Standard Deviation 12.7

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=53 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate During the Co-administration Period Change at V11	-2.8 bpm Standard Deviation 11.0
Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate During the Co-administration Period Change at LVA	-2.2 bpm Standard Deviation 11.2

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=53 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period PR Interval: Change at V11	1.1 milliseconds (ms) Standard Deviation 15.8
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period PR Interval: Change at LVA	1.3 milliseconds (ms) Standard Deviation 15.5
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period QRS Interval: Change at V11	0.1 milliseconds (ms) Standard Deviation 10.1
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period QRS Interval: Change at LVA	0.3 milliseconds (ms) Standard Deviation 10.1
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period QT Interval: Change at V11	4.0 milliseconds (ms) Standard Deviation 29.7
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period QT Interval: Change at LVA	2.4 milliseconds (ms) Standard Deviation 29.9
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period RR Interval: Change at V11	34.7 milliseconds (ms) Standard Deviation 175.4
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period RR Interval: Change at LVA	27.6 milliseconds (ms) Standard Deviation 174.8
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period QTcF: Change at V11	-1.8 milliseconds (ms) Standard Deviation 16.9
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period QTcF: Change at LVA	-2.2 milliseconds (ms) Standard Deviation 16.6

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period Resolved Lithiasis: LVA vs V3	1 participants
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period Developed Sludge: V11 vs V3	3 participants
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period Resolved Sludge: V11 vs V3	5 participants
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period Developed Lithiasis: V11 vs V3	1 participants
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period Resolved Lithiasis: V11 vs V3	1 participants
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period Developed Sludge: LVA vs V3	3 participants
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period Resolved Sludge: LVA vs V3	5 participants
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period Developed Lithiasis: LVA vs V3	2 participants

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=53 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean Pituitary Tumour Size During the Co-administration Period Change at V11	2.4 mm^3 Standard Deviation 729.7
Change From Baseline in Mean Pituitary Tumour Size During the Co-administration Period Change at LVA	6.3 mm^3 Standard Deviation 707.6

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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 blood glucose Cmax (as determined from OGTT) from Baseline to V11 and to LVA is presented.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=38 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean Blood Glucose Maximum Concentration (Cmax) From Oral Glucose Tolerance Test (OGTT) During the Co-administration Period; Assessed in Non Diabetic Subjects Change at V11	0.53 millimoles per litre (mmol/L) Standard Deviation 1.72
Change From Baseline in Mean Blood Glucose Maximum Concentration (Cmax) From Oral Glucose Tolerance Test (OGTT) During the Co-administration Period; Assessed in Non Diabetic Subjects Change at LVA	0.61 millimoles per litre (mmol/L) Standard Deviation 1.69

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=36 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean Fasting Insulin Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects Change at V11	-12.7 picomoles per litre (pmol/L) Standard Deviation 41.5
Change From Baseline in Mean Fasting Insulin Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects Change at LVA	-11.7 picomoles per litre (pmol/L) Standard Deviation 40.8

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=36 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean Fasting Glucose Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects Change at V11	-0.05 mmol/L Standard Deviation 0.71
Change From Baseline in Mean Fasting Glucose Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects Change at LVA	-0.09 mmol/L Standard Deviation 0.69

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=34 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean Fasting Insulin / Glucose Ratio During the Co-administration Period; Assessed in Non Diabetic Subjects Change at V11	-2.61 ratio Standard Deviation 8.12
Change From Baseline in Mean Fasting Insulin / Glucose Ratio During the Co-administration Period; Assessed in Non Diabetic Subjects Change at LVA	-2.33 ratio Standard Deviation 7.94

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=56 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Mean Glycosylated Haemoglobin (HbA1C) During the Co-administration Period; Assessed in Non Diabetic and Diabetic Subjects Diabetic Subjects: Change at LVA	-0.05 percentage Standard Deviation 0.69
Change From Baseline in Mean Glycosylated Haemoglobin (HbA1C) During the Co-administration Period; Assessed in Non Diabetic and Diabetic Subjects Diabetic Subjects: Change at V11	-0.05 percentage Standard Deviation 0.71
Change From Baseline in Mean Glycosylated Haemoglobin (HbA1C) During the Co-administration Period; Assessed in Non Diabetic and Diabetic Subjects Non Diabetic Subjects: Change at V11	0.05 percentage Standard Deviation 0.20
Change From Baseline in Mean Glycosylated Haemoglobin (HbA1C) During the Co-administration Period; Assessed in Non Diabetic and Diabetic Subjects Non Diabetic Subjects: Change at LVA	0.05 percentage Standard Deviation 0.21

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Liver Function Test Parameters During the Co-administration Period AST: Change at V11	3.3 IU/L Standard Deviation 10.7
Change From Baseline in Liver Function Test Parameters During the Co-administration Period AST: Change at LVA	4.5 IU/L Standard Deviation 13.0
Change From Baseline in Liver Function Test Parameters During the Co-administration Period ALT: Change at V11	4.1 IU/L Standard Deviation 11.7
Change From Baseline in Liver Function Test Parameters During the Co-administration Period ALT: Change at LVA	7.8 IU/L Standard Deviation 23.2
Change From Baseline in Liver Function Test Parameters During the Co-administration Period GGT: Change at V11	-1.0 IU/L Standard Deviation 17.8
Change From Baseline in Liver Function Test Parameters During the Co-administration Period GGT: Change at LVA	1.5 IU/L Standard Deviation 20.8
Change From Baseline in Liver Function Test Parameters During the Co-administration Period Alkaline Phosphatase: Change at V11	-1.7 IU/L Standard Deviation 14.5
Change From Baseline in Liver Function Test Parameters During the Co-administration Period Alkaline Phosphatase: Change at LVA	-0.8 IU/L Standard Deviation 15.4

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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. The change in mean total bilirubin from Baseline to V11 and to LVA is presented.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Total Bilirubin During the Co-administration Period Change at V11	-1.3 micromoles per litre Standard Deviation 2.9
Change From Baseline in Total Bilirubin During the Co-administration Period Change at LVA	-1.2 micromoles per litre Standard Deviation 2.8

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Prothrombin Time (Expressed as a Percentage of Normal) During the Co-administration Period Change at V11	-3.7 percentage of time Standard Deviation 16.0
Change From Baseline in Prothrombin Time (Expressed as a Percentage of Normal) During the Co-administration Period Change at LVA	-3.6 percentage of time Standard Deviation 15.2

SECONDARY outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Number of Subjects With Putative Antibodies to Lanreotide and to Pegvisomant During the Co-administration Period Antibodies for Lanreotide	4 Number of subjects
Number of Subjects With Putative Antibodies to Lanreotide and to Pegvisomant During the Co-administration Period Antibodies for Pegvisomant	6 Number of subjects

OTHER_PRE_SPECIFIED outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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 change in mean serum GH levels from Baseline to V11 and to LVA is presented.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Serum GH Levels During the Co-administration Period Change at V11	6.6 nanograms per millilitre (ng/mL) Standard Deviation 9.9
Change From Baseline in Serum GH Levels During the Co-administration Period Change at LVA	6.6 nanograms per millilitre (ng/mL) Standard Deviation 9.7

OTHER_PRE_SPECIFIED outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Percentage of Subjects With Serum GH Levels Lesser or Equal to 2.5 ng/mL During the Study At V3	38.6 percentage of subjects
Percentage of Subjects With Serum GH Levels Lesser or Equal to 2.5 ng/mL During the Study At V11	25.0 percentage of subjects
Percentage of Subjects With Serum GH Levels Lesser or Equal to 2.5 ng/mL During the Study At LVA	22.8 percentage of subjects

OTHER_PRE_SPECIFIED outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Serum GH Binding Protein Levels During the Co-administration Period Change at V11	841 pmol/L Standard Deviation 302
Change From Baseline in Serum GH Binding Protein Levels During the Co-administration Period Change at LVA	811 pmol/L Standard Deviation 320

OTHER_PRE_SPECIFIED outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Acid Labile Subunit Levels From Baseline During the Co-administration Period Change at V11	-561 milli IU per millilitre (mIU/mL) Standard Deviation 528
Change From Baseline in Acid Labile Subunit Levels From Baseline During the Co-administration Period Change at LVA	-541 milli IU per millilitre (mIU/mL) Standard Deviation 522

OTHER_PRE_SPECIFIED outcome

Timeframe: V3 (Week 12; Baseline) up to V11 (Week 44)

Population: 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.

Outcome measures

Outcome measures
Measure	Lanreotide Autogel + Pegvisomant Co-administration n=57 Participants Eligible subjects were entered into the co-administration period during which they received both lanreotide Autogel and pegvisomant concomitantly for 28 weeks. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg and was administered by one deep s.c. injection every 28 days. Pegvisomant was administered once or twice a week via s.c. injection. The starting dose was 60 mg once a week dose. Dose adaptation of pegvisomant could then be made every 8 weeks based on IGF-1 levels taken 4 weeks after previous dose adaptation and by the third titration, subjects could receive either 40 mg, 60 mg or 80 mg once a week or 40 mg or 60 mg twice per week.
Change From Baseline in Prolactin Levels During the Co-administration Period Change at V11	-0.1 micrograms per litre (mcg/L) Standard Deviation 8.9
Change From Baseline in Prolactin Levels During the Co-administration Period Change at LVA	-0.4 micrograms per litre (mcg/L) Standard Deviation 8.8

Adverse Events

Run-in Period

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Co-administration Period

Serious events: 8 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director, Endocrinology

Ipsen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Run-in Period n=57 participants at risk During the 16 week run-in period, eligible subjects received one injection of lanreotide Autogel 120 mg every 28 days, administered by deep s.c. injection.	Co-administration Period n=57 participants at risk During the 28 week co-administration period, eligible subjects received both lanreotide Autogel and pegvisomant concomitantly. The lanreotide Autogel dose during the co-administration period was fixed at 120 mg. Pegvisomant was administered once or twice a week via s.c. injection and the dose of could be adapted every 8 weeks based on IGF-1 levels, following a starting dose of 60 mg once a week (dose could vary from 40 to 120 mg per week and maximum permitted dose was 60 mg twice a week).
Endocrine disorders Adrenocortical insufficiency acute	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Infections and infestations Wound infection	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
General disorders Impaired healing	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Nervous system disorders Amnesia	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Nervous system disorders Facial palsy	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Nervous system disorders Petit mal epilepsy	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Nervous system disorders Transient ischaemic attack	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Gastrointestinal disorders Abdominal pain	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Gastrointestinal disorders Vomiting	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Renal and urinary disorders Renal failure	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Renal and urinary disorders Renal colic	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).
Cardiac disorders Atrial fibrillation	0.00% 0/57 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).	1.8% 1/57 • Number of events 1 • Run-in Period: approximately 16 weeks and Co-administration Period: approximately 28 weeks. Adverse event (AE) data is reported as treatment-emergent AEs for both the run-in and co-administration periods and is presented for the Safety Population, defined as all subjects who received at least one dose of each IMP (i.e. one dose of lanreotide Autogel 120 mg and one dose of pegvisomant during the co-administration period).