Back to resultsLanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients
Primary Purpose
Acromegaly
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
lanreotide (Autogel formulation)
Pegvisomant
Sponsored by
About this trial
This is an interventional treatment trial for Acromegaly
Eligibility Criteria
Inclusion Criteria:
- The patient must have had documentation supporting the diagnosis of acromegaly, including elevated GH and/or IGF-1 levels
- The patient is treated with pegvisomant, because of IGF-1 level remaining above ULN when treated with somatostatin analogue, on a daily basis for at least 3 months and has normal (age and sex adjusted) IGF-1 level, or IGF-1 level above the upper limit of normal (ULN) after treatment with pegvisomant 30 mg per day, OR the patient is treated with lanreotide Autogel or octreotide LAR for at least 6 months including 3 months at the highest marketed dose and has a serum IGF-1 level above ULN, 28 days after the last injection
- At the end of the run-in period, The patient has a serum IGF-1 level above 1.2 x ULN, or a serum IGF-1 level between ULN and 1.2 x ULN and a serum GH nadir > 1 µg/L (assessed by an OGTT), 28 days after the 3rd injection of lanreotide Autogel 120 mg OR the patient is diabetic and has a serum IGF-1 level above 1.2 ULN, 28 days after the 3rd injection of lanreotide Autogel 120 mg
Exclusion Criteria:
- The patient has undergone pituitary surgery or radiotherapy within 6 months prior to study entry, or it is anticipated that it will be done during the study
- The patient has already been treated with a somatostatin analogue associated with a GH antagonist
- The patient has received dopamine agonist within 6 weeks prior to the study entry
- The patient has abnormal hepatic function at study entry (defined as AST, ALT, GGT, alkaline phosphatase, prothrombin time or total bilirubin above 2 ULN)
- The patient is at risk of pregnancy or is lactating
Sites / Locations
- University Hospital, Charles University
- Charles University
- Aarhus Kommunehospital
- Groupe Hospitalier Henri Mondor- Albert Chenevier
- Hôpital Bicêtre
- Clinique Marc Linquette
- Hôpital de la Timone
- CHU de Rangueil
- Charite Campus Mitte
- Klinikum Johann Wolfgang Goethe-Universität
- Medizinische Klinik Innenstadt
- Anticancer Hospital Metaxa Piraeus
- Universitá degli Studi di Milano
- University Federico II
- Universitá di Torino
- Leiden University Medical Center
- Dept. of Internal Medicine Erasmus MC
- Hospital General de Alicante
- Clínica Puerta de Hierro
- Hospital Clínico Universitario de Santiago de Compostela
- Sahlgrenska University Hospital
- Uppsala University Hospital
- Christie Hospital and Holt Radium Institute
- Royal Hallamshire Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period
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.
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
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.
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
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.
Secondary Outcome Measures
Percentage of Subjects With a Normalised (Age and Sex Adjusted) IGF-1 Level at Any Time During the Co-administration Period
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.
Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment
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.
Change From Baseline in Serum IGF-1 Levels (Expressed as Z-scores) During the Co-administration Period
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.
Change From Baseline in Acromegaly Symptoms During the Co-administration Period
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.
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period
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.
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
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.
Change From Baseline in Mean Weight From Baseline During the Co-administration Period
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.
Change From Baseline in Mean Supine Systolic and Diastolic Blood Pressure (BP) During the Co-administration Period
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.
Change From Baseline in Mean Supine Heart Rate During the Co-administration Period
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.
Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate During the Co-administration Period
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.
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period
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.
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period
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.
Change From Baseline in Mean Pituitary Tumour Size During the Co-administration Period
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.
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
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.
Change From Baseline in Mean Fasting Insulin Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects
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.
Change From Baseline in Mean Fasting Glucose Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects
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.
Change From Baseline in Mean Fasting Insulin / Glucose Ratio During the Co-administration Period; Assessed in Non Diabetic Subjects
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.
Change From Baseline in Mean Glycosylated Haemoglobin (HbA1C) During the Co-administration Period; Assessed in Non Diabetic and 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.
Change From Baseline in Liver Function Test Parameters During the Co-administration Period
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.
Change From Baseline in Total Bilirubin During the Co-administration Period
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.
Change From Baseline in Prothrombin Time (Expressed as a Percentage of Normal) During the Co-administration Period
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.
Number of Subjects With Putative Antibodies to Lanreotide and to Pegvisomant During the Co-administration Period
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00383708
Brief Title
Lanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients
Official Title
Phase III, Multicentre, Open Study to Assess the Efficacy and Safety Profiles of the Co-administration of Lanreotide Autogel 120 mg (Administered Via Deep Subcutaneous Injections Every 28 Days) and Pegvisomant 40 to 120 mg Per Week (Administered Via Subcutaneous Route Once or Twice a Week) in Acromegalic Patients Failing to Respond to Lanreotide Autogel 120 mg Alone
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ipsen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main aim of this study is to assess the efficacy of the co-administration of lanreotide Autogel 120 mg (administered via deep sub-cutaneous injections every 28 days) and pegvisomant (administered at 40 to 120 mg per week via sub-cutaneous injection given once or twice a week) on IGF-1 levels over 28 weeks in acromegalic patients. The primary endpoint will be the percentage of acromegalic patients with normalised (age and sex adjusted) IGF-1 level at the end of the co-treatment period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acromegaly
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
125 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
lanreotide (Autogel formulation)
Intervention Description
120 mg administered via deep subcutaneous injection every 28 days over 28 weeks.
Intervention Type
Drug
Intervention Name(s)
Pegvisomant
Intervention Description
Administered at 40 to 120 mg per week via subcutaneous injection once or twice a week over 28 weeks.
Primary Outcome Measure Information:
Title
Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
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
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
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
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Secondary Outcome Measure Information:
Title
Percentage of Subjects With a Normalised (Age and Sex Adjusted) IGF-1 Level at Any Time During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment
Description
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.
Time Frame
V1 (Screening) up to V11 (Week 44)
Title
Change From Baseline in Serum IGF-1 Levels (Expressed as Z-scores) During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Acromegaly Symptoms During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
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
Description
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.
Time Frame
At V2 (Day 1; Run-in), V3 (Week 12; Baseline) and V11 (Week 44)
Title
Change From Baseline in Mean Weight From Baseline During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Mean Supine Systolic and Diastolic Blood Pressure (BP) During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Mean Supine Heart Rate During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Mean Pituitary Tumour Size During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
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
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Mean Fasting Insulin Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Mean Fasting Glucose Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Mean Fasting Insulin / Glucose Ratio During the Co-administration Period; Assessed in Non Diabetic Subjects
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Mean Glycosylated Haemoglobin (HbA1C) During the Co-administration Period; Assessed in Non Diabetic and Diabetic Subjects
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Liver Function Test Parameters During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Total Bilirubin During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Prothrombin Time (Expressed as a Percentage of Normal) During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Number of Subjects With Putative Antibodies to Lanreotide and to Pegvisomant During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Other Pre-specified Outcome Measures:
Title
Change From Baseline in Serum GH Levels During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Percentage of Subjects With Serum GH Levels Lesser or Equal to 2.5 ng/mL During the Study
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Serum GH Binding Protein Levels During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Acid Labile Subunit Levels From Baseline During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
Title
Change From Baseline in Prolactin Levels During the Co-administration Period
Description
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.
Time Frame
V3 (Week 12; Baseline) up to V11 (Week 44)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient must have had documentation supporting the diagnosis of acromegaly, including elevated GH and/or IGF-1 levels
The patient is treated with pegvisomant, because of IGF-1 level remaining above ULN when treated with somatostatin analogue, on a daily basis for at least 3 months and has normal (age and sex adjusted) IGF-1 level, or IGF-1 level above the upper limit of normal (ULN) after treatment with pegvisomant 30 mg per day, OR the patient is treated with lanreotide Autogel or octreotide LAR for at least 6 months including 3 months at the highest marketed dose and has a serum IGF-1 level above ULN, 28 days after the last injection
At the end of the run-in period, The patient has a serum IGF-1 level above 1.2 x ULN, or a serum IGF-1 level between ULN and 1.2 x ULN and a serum GH nadir > 1 µg/L (assessed by an OGTT), 28 days after the 3rd injection of lanreotide Autogel 120 mg OR the patient is diabetic and has a serum IGF-1 level above 1.2 ULN, 28 days after the 3rd injection of lanreotide Autogel 120 mg
Exclusion Criteria:
The patient has undergone pituitary surgery or radiotherapy within 6 months prior to study entry, or it is anticipated that it will be done during the study
The patient has already been treated with a somatostatin analogue associated with a GH antagonist
The patient has received dopamine agonist within 6 weeks prior to the study entry
The patient has abnormal hepatic function at study entry (defined as AST, ALT, GGT, alkaline phosphatase, prothrombin time or total bilirubin above 2 ULN)
The patient is at risk of pregnancy or is lactating
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ipsen Medical Director
Organizational Affiliation
Ipsen
Official's Role
Study Director
Facility Information:
Facility Name
University Hospital, Charles University
City
Hradec Kralove
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Charles University
City
Prague
ZIP/Postal Code
120 00 PRAHA 2
Country
Czechia
Facility Name
Aarhus Kommunehospital
City
Aarhus
Country
Denmark
Facility Name
Groupe Hospitalier Henri Mondor- Albert Chenevier
City
Créteil Cedex
Country
France
Facility Name
Hôpital Bicêtre
City
Le Kremlin-Bicêtre
ZIP/Postal Code
94275
Country
France
Facility Name
Clinique Marc Linquette
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital de la Timone
City
Marseille Cedex
ZIP/Postal Code
13385
Country
France
Facility Name
CHU de Rangueil
City
Toulouse
ZIP/Postal Code
31054
Country
France
Facility Name
Charite Campus Mitte
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Klinikum Johann Wolfgang Goethe-Universität
City
Frankfurt
ZIP/Postal Code
605090
Country
Germany
Facility Name
Medizinische Klinik Innenstadt
City
Munchen
ZIP/Postal Code
80336
Country
Germany
Facility Name
Anticancer Hospital Metaxa Piraeus
City
Piraeus
ZIP/Postal Code
18537
Country
Greece
Facility Name
Universitá degli Studi di Milano
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
University Federico II
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Universitá di Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
Facility Name
Dept. of Internal Medicine Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015 GD
Country
Netherlands
Facility Name
Hospital General de Alicante
City
Alicante
ZIP/Postal Code
03012
Country
Spain
Facility Name
Clínica Puerta de Hierro
City
Madrid
ZIP/Postal Code
28035
Country
Spain
Facility Name
Hospital Clínico Universitario de Santiago de Compostela
City
Santiago de Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Sahlgrenska University Hospital
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Uppsala University Hospital
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Name
Christie Hospital and Holt Radium Institute
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.
Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
IPD Sharing Time Frame
Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
IPD Sharing Access Criteria
Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
IPD Sharing URL
https://vivli.org/members/ourmembers/
Citations:
PubMed Identifier
21148630
Citation
van der Lely AJ, Bernabeu I, Cap J, Caron P, Colao A, Marek J, Neggers S, Birman P. Coadministration of lanreotide Autogel and pegvisomant normalizes IGF1 levels and is well tolerated in patients with acromegaly partially controlled by somatostatin analogs alone. Eur J Endocrinol. 2011 Mar;164(3):325-33. doi: 10.1530/EJE-10-0867. Epub 2010 Dec 10.
Results Reference
result
Learn more about this trial
Lanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients
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