Phase 3
Completed N=125
Lanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients
Acromegaly
Source: ClinicalTrials.gov NCT00383708 ↗
Enrolled (actual)
125
Serious AEs
8.8%
Results posted
Jul 2018
Primary outcomePrimary: 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
◆ Published Evidence
Established
85citations · ~6 / year
Coadministration of lanreotide Autogel and pegvisomant normalizes IGF1 levels and is well tolerated in patients with acromegaly partially controlled by somatostatin analogs alone.
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.
Linked Publications
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Coadministration of lanreotide Autogel and pegvisomant normalizes IGF1 levels and is well tolerated in patients with acromegaly partially controlled by somatostatin analogs alone.
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 | — |
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) and the linked publication. 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. Informational only — not medical advice.