Efficacy/Safety of Octreotide Acetate in Patients With Uncontrolled Acromegaly

Study Overview
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Brief Summary
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This study evaluated the safety and efficacy of an increased frequency of octreotide acetate injections or an increase in dose in partially responsive acromegalic patients with persistently uncontrolled disease.

Official Title
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A Randomised, Open-label, Multicenter Study Comparing the Efficacy and Safety of Medical Treatment With Octreotide Acetate 30 mg Administered Every 21 Days for 6 Months With That of Octreotide Acetate 60 mg Administered Every 28 Days for 6 Months in Acromegalic Patients With Uncontrolled Disease

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: Octreotide acetate 30 mg suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written voluntary informed consent. Patients with biochemically documented active acromegaly who are currently receiving somatostatin-analogues in a conventional treatment regimen (octreotide up to 30 mg/28 days; lanreotide up to 120 mg/28 days) for at least 6 months. Patients with uncontrolled disease defined as patients with a decrease of baseline levels of growth hormone (GH) ≥ 50% during treatment with somatostatin-analogues in a conventional regimen (sandostatin up to 30 mg/28 days; lanreotide up to 120 mg/28 days) for at least 6 months. Baseline (mean of 3 samples) GH level > 2 µg/L. Insulin-like Growth Factor I (IGF-I) levels above the upper limits of normal for age and gender. Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Octreotide 30 mg every 21 days<br>Patients received octreotide 30 mg every 21 days intramuscularly (im) for 6 months, a total of 8 doses. At each study visit, octreotide was administered only after completion of all scheduled efficacy and safety evaluations for that visit. Octreotide was injected im into the right or left gluteal regions. The injections were initially administered by a trained and authorized member of the investigational team. When no study visit at the investigational site was required, the injections were given by a trained nurse or the family doctor. | Drug: Octreotide acetate 30 mg suspension<br>* Each vial of study medication contained octreotide acetate 30 mg in a microencapsulated biodegradable polymer, poly (DL-lactide-co-glycolide) (D-(+)glucose), with 17% w/w mannitol in an approximate octreotide:polymer ratio of 1:20. The vehicle contained 0.5% sodium carboxymethylcellulose.<br>* Other names: Sandostatin LAR;|
| Experimental: Octreotide 60 mg every 28 days<br>Patients received octreotide 60 mg every 28 days intramuscularly (im) for 6 months, a total of 6 doses. Octreotide mg was administered as two 30 mg injections. At each study visit, octreotide was administered only after completion of all scheduled efficacy and safety evaluations for that visit. Octreotide was injected im into the right or left gluteal regions. The injections were initially administered by a trained and authorized member of the investigational team. When no study visit at the investigational site was required, the injections were given by a trained nurse or the family doctor. | Drug: Octreotide acetate 30 mg suspension<br>* Each vial of study medication contained octreotide acetate 30 mg in a microencapsulated biodegradable polymer, poly (DL-lactide-co-glycolide) (D-(+)glucose), with 17% w/w mannitol in an approximate octreotide:polymer ratio of 1:20. The vehicle contained 0.5% sodium carboxymethylcellulose.<br>* Other names: Sandostatin LAR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Growth Hormone (GH) Level From Screening to End of Study (Week 24) | Growth hormone (GH) level was the average value measured in 3 blood samples collected at 15 minute intervals at each visit. GH was measured with an automated immunometric assay in a central laboratory. | Screening to end of study (Week 24) | 
| Change in Insulin-like Growth Factor 1 (IGF-1) Level From Screening to End of Study (Week 24) | Insulin-like growth factor 1 (IGF-1) level was measured in a blood sample with an automated immunometric assay in a central laboratory. | Screening to end of study (Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tumor Volume From Screening to End of Study (Week 24) | A pre-treatment magnetic resonance image (MRI) assessment of the pituitary area was required within 12 weeks prior to Screening as a baseline evaluation. A second MRI was performed at the end of the study (Week 24). All MRIs were performed according to protocol-defined guidelines. The tumor volume (mm^3) was calculated from measurements obtained in 3 axes from the MRI images. | Screening to end of study (Week 24) | 
| Percentage of Participants With > 20% Tumor Shrinkage From Screening to End of Study (Week 24) | A pre-treatment magnetic resonance image (MRI) assessment of the pituitary area was required within 12 weeks prior to Screening as a baseline evaluation. A second MRI was performed at the end of the study (Week 24). All MRIs were performed according to protocol-defined guidelines. The tumor volume (mm^3) was calculated from measurements obtained in 3 axes from the MRI images. | Screening to end of study (Week 24) | 
| Percentage of Participants Asymptomatic for Acromegaly Symptoms at Week 12 and End of Study (Week 24) | The investigator asked the participant to score the following symptoms of acromegaly: Headache, perspiration, paresthesia, fatigue, osteoarthralgia, and carpal tunnel syndrome on a 5-point scale (0=absent; 1=mild; 2=moderate; 3=severe, but not disabling; 4=severe and disabling). The percentage of asymptomatic participants, ie, with a score of 0 for all symptoms, was calculated. | Week 12 and end of study (Week 24) | 
| Acromegaly Quality of Life (AcroQoL) Questionnaire Physical Scale Score at End of Study (Week 24) | The AcroQoL contains 8 items on Physical aspects. Participants were asked to rate each item on a 1-5 Likert scale measuring either the frequency of occurrence (always, most of the time, sometimes, rarely, or never) or the degree of agreement (completely agree, moderately agree, neither agree nor disagree, moderately disagree, completely disagree). The score on the physical scale can range from 8-40. A higher score indicates better Quality of Life. | End of study (Week 24) | 
| Acromegaly Quality of Life (AcroQoL) Questionnaire Psychological Scale Score at End of Study (Week 24) | The AcroQoL contains 14 items on Psychological aspects. Participants were asked to rate each item on a 1-5 Likert scale measuring either the frequency of occurrence (always, most of the time, sometimes, rarely, or never) or the degree of agreement (completely agree, moderately agree, neither agree nor disagree, moderately disagree, completely disagree). The score on the psychological scale ranges from 14-70. A higher score indicates better Quality of Life. | End of study (Week 24) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acromegaly, octreotide acetate, partial responder patients