Clinical trial NCT00383708: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acromegaly
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2006-10-03
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Subjects With Acromegaly With a Normalised (Age and Sex Adjusted) IGF-1 Level at the End of the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: 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
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: 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
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
Secondary outcomes:
measure: Percentage of Subjects With a Normalised (Age and Sex Adjusted) IGF-1 Level at Any Time During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment
timeFrame: V1 (Screening) up to V11 (Week 44)
measure: Change From Baseline in Serum IGF-1 Levels (Expressed as Z-scores) During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Acromegaly Symptoms During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: 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
timeFrame: At V2 (Day 1; Run-in), V3 (Week 12; Baseline) and V11 (Week 44)
measure: Change From Baseline in Mean Weight From Baseline During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Mean Supine Systolic and Diastolic Blood Pressure (BP) During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Mean Supine Heart Rate During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Mean Pituitary Tumour Size During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: 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
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Mean Fasting Insulin Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Mean Fasting Glucose Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Mean Fasting Insulin / Glucose Ratio During the Co-administration Period; Assessed in Non Diabetic Subjects
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Mean Glycosylated Haemoglobin (HbA1C) During the Co-administration Period; Assessed in Non Diabetic and Diabetic Subjects
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Liver Function Test Parameters During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Total Bilirubin During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Prothrombin Time (Expressed as a Percentage of Normal) During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Number of Subjects With Putative Antibodies to Lanreotide and to Pegvisomant During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
Other outcomes:
measure: Change From Baseline in Serum GH Levels During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Percentage of Subjects With Serum GH Levels Lesser or Equal to 2.5 ng/mL During the Study
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Serum GH Binding Protein Levels During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Acid Labile Subunit Levels From Baseline During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
measure: Change From Baseline in Prolactin Levels During the Co-administration Period
timeFrame: V3 (Week 12; Baseline) up to V11 (Week 44)
Locations:
city: Hradec Kralove
country: Czechia
facility: University Hospital, Charles University
city: Prague
country: Czechia
facility: Charles University
city: Aarhus
country: Denmark
facility: Aarhus Kommunehospital
city: Créteil Cedex
country: France
facility: Groupe Hospitalier Henri Mondor- Albert Chenevier
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
city: Lille Cedex
country: France
facility: Clinique Marc Linquette
city: Marseille Cedex
country: France
facility: Hôpital de la Timone
city: Toulouse
country: France
facility: CHU de Rangueil
city: Berlin
country: Germany
facility: Charite Campus Mitte
city: Frankfurt
country: Germany
facility: Klinikum Johann Wolfgang Goethe-Universität
city: Munchen
country: Germany
facility: Medizinische Klinik Innenstadt
city: Piraeus
country: Greece
facility: Anticancer Hospital Metaxa Piraeus
city: Milano
country: Italy
facility: Universitá degli Studi di Milano
city: Napoli
country: Italy
facility: University Federico II
city: Torino
country: Italy
facility: Universitá di Torino
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Dept. of Internal Medicine Erasmus MC
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Madrid
country: Spain
facility: Clínica Puerta de Hierro
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital and Holt Radium Institute
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
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.