Phase 3
N=125
Lanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients
Acromegaly
Bottom Line
View on ClinicalTrials.gov: NCT00383708 ↗Enrolled (actual)
125
Serious AEs
8.8%
Results posted
Jul 2018
Primary outcome: Primary: 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 — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- lanreotide (Autogel formulation) (Drug); Pegvisomant (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Ipsen
- Primary completion
- Oct 2008
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 | <0.0001 sig |
| PRIMARY 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 |
46.2; 54.2; 70.0; 76.9; 61.5; 75.0 | 0.1654 |
| PRIMARY 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 |
47.4; 63.2 | 0.084 |
| SECONDARY Percentage of Subjects With a Normalised (Age and Sex Adjusted) IGF-1 Level at Any Time During the Co-administration Period |
66.7; 78.9 | <0.0001 sig |
| SECONDARY Percentage of Subjects With Normalised (Age and Sex Adjusted) IGF-1 at Each Assessment |
17.5; 24.5; 56.4; 48.1; 57.7; 61.5 | — |
| SECONDARY Change From Baseline in Serum IGF-1 Levels (Expressed as Z-scores) During the Co-administration Period |
-4.50; -4.25 | — |
| SECONDARY Change From Baseline in Acromegaly Symptoms During the Co-administration Period |
-0.7; -0.6; -0.4; -0.4; -0.2; -0.2 | — |
| SECONDARY Change From Baseline in Acromegaly Quality of Life (ACROQoL) Assessments During the Co-administration Period |
2.4; 2.2; 4.2; 3.5; 1.3; 1.4 | — |
| SECONDARY 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 |
-0.16; 0.09; -0.17; 0.14; -0.1; 0.08 | — |
| SECONDARY Change From Baseline in Mean Weight From Baseline During the Co-administration Period |
-0.3; -0.3 | — |
| SECONDARY Change From Baseline in Mean Supine Systolic and Diastolic Blood Pressure (BP) During the Co-administration Period |
-0.4; 0.2; -0.1; -0.3 | — |
| SECONDARY Change From Baseline in Mean Supine Heart Rate During the Co-administration Period |
-3.1; -2.5 | — |
| SECONDARY Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate During the Co-administration Period |
-2.8; -2.2 | — |
| SECONDARY Change From Baseline in Mean PR Interval, QRS Interval, QT Interval, RR Interval and QTcF During the Co-administration Period |
1.1; 1.3; 0.1; 0.3; 4.0; 2.4 | — |
| SECONDARY Number of Subjects With Shift in Presence/Absence of Lithiasis and/or Sludge During Co-administration Period |
3; 5; 1; 1; 3; 5 | — |
| SECONDARY Change From Baseline in Mean Pituitary Tumour Size During the Co-administration Period |
2.4; 6.3 | — |
| SECONDARY 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 |
0.53; 0.61 | — |
| SECONDARY Change From Baseline in Mean Fasting Insulin Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects |
-12.7; -11.7 | — |
| SECONDARY Change From Baseline in Mean Fasting Glucose Concentration During the Co-administration Period; Assessed in Non Diabetic Subjects |
-0.05; -0.09 | — |
| SECONDARY Change From Baseline in Mean Fasting Insulin / Glucose Ratio During the Co-administration Period; Assessed in Non Diabetic Subjects |
-2.61; -2.33 | — |
| SECONDARY Change From Baseline in Mean Glycosylated Haemoglobin (HbA1C) During the Co-administration Period; Assessed in Non Diabetic and Diabetic Subjects |
-0.05; -0.05; 0.05; 0.05 | — |
| SECONDARY Change From Baseline in Liver Function Test Parameters During the Co-administration Period |
3.3; 4.5; 4.1; 7.8; -1.0; 1.5 | — |
| SECONDARY Change From Baseline in Total Bilirubin During the Co-administration Period |
-1.3; -1.2 | — |
| SECONDARY Change From Baseline in Prothrombin Time (Expressed as a Percentage of Normal) During the Co-administration Period |
-3.7; -3.6 | — |
| SECONDARY Number of Subjects With Putative Antibodies to Lanreotide and to Pegvisomant During the Co-administration Period |
4; 6 | — |
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
Data sourced from ClinicalTrials.gov (NCT00383708). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.