Acromegaly
Conditions
Keywords
acromegaly, octreotide acetate, partial responder patients
Brief summary
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.
Interventions
DRUGOctreotide acetate 30 mg suspension
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Growth Hormone (GH) Level From Screening to End of Study (Week 24) | 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. |
| Change in Insulin-like Growth Factor 1 (IGF-1) Level From Screening to End of Study (Week 24) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Asymptomatic for Acromegaly Symptoms at Week 12 and End of Study (Week 24) | 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. |
| Change in Tumor Volume From Screening to End of Study (Week 24) | 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. |
| Acromegaly Quality of Life (AcroQoL) Questionnaire Psychological Scale Score at End of Study (Week 24) | 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. |
| Acromegaly Quality of Life (AcroQoL) Questionnaire Physical Scale Score at End of Study (Week 24) | 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. |
| Percentage of Participants With > 20% Tumor Shrinkage From Screening to End of Study (Week 24) | 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. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Octreotide 30 mg Every 21 Days Participants 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. | 16 |
| Octreotide 60 mg Every 28 Days Participants 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. | 12 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 1 |
Baseline characteristics
| Characteristic | Octreotide 30 mg Every 21 Days | Octreotide 60 mg Every 28 Days | Total |
|---|---|---|---|
| Age Continuous | 51.3 years STANDARD_DEVIATION 12.1 | 51.8 years STANDARD_DEVIATION 15.7 | 51.5 years STANDARD_DEVIATION 13.9 |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 16 | 2 / 12 |
| serious Total, serious adverse events | 0 / 16 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Screening to end of study (Week 24)
Population: Intent-to-treat (ITT) population included all participants who received at least one dose of study medication and who had at least one post-baseline evaluation of the primary variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octreotide 30 mg Every 21 Days | Change in Growth Hormone (GH) Level From Screening to End of Study (Week 24) | -1.7 µg/L | Standard Deviation 9.9 |
| Octreotide 60 mg Every 28 Days | Change in Growth Hormone (GH) Level From Screening to End of Study (Week 24) | -2.1 µg/L | Standard Deviation 3.6 |
Primary
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.
Time frame: Screening to end of study (Week 24)
Population: Intent-to-treat (ITT) population included all participants who received at least one dose of study medication and who had at least one post-baseline evaluation of the primary variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octreotide 30 mg Every 21 Days | Change in Insulin-like Growth Factor 1 (IGF-1) Level From Screening to End of Study (Week 24) | -40.4 µg/L | Standard Deviation 180.2 |
| Octreotide 60 mg Every 28 Days | Change in Insulin-like Growth Factor 1 (IGF-1) Level From Screening to End of Study (Week 24) | -135.0 µg/L | Standard Deviation 170.9 |
Secondary
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.
Time frame: End of study (Week 24)
Population: Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of assigned study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octreotide 30 mg Every 21 Days | Acromegaly Quality of Life (AcroQoL) Questionnaire Physical Scale Score at End of Study (Week 24) | 67.9 Percent of maximum score | Standard Deviation 22.6 |
| Octreotide 60 mg Every 28 Days | Acromegaly Quality of Life (AcroQoL) Questionnaire Physical Scale Score at End of Study (Week 24) | 58.0 Percent of maximum score | Standard Deviation 21.8 |
Secondary
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.
Time frame: End of study (Week 24)
Population: Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of assigned study medication and who had data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octreotide 30 mg Every 21 Days | Acromegaly Quality of Life (AcroQoL) Questionnaire Psychological Scale Score at End of Study (Week 24) | 65.1 Percent of maximum score | Standard Deviation 19.9 |
| Octreotide 60 mg Every 28 Days | Acromegaly Quality of Life (AcroQoL) Questionnaire Psychological Scale Score at End of Study (Week 24) | 72.1 Percent of maximum score | Standard Deviation 19.6 |
Secondary
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.
Time frame: Screening to end of study (Week 24)
Population: Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of assigned study medication and who had data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octreotide 30 mg Every 21 Days | Change in Tumor Volume From Screening to End of Study (Week 24) | 15.9 mm^3 | Standard Deviation 91.8 |
| Octreotide 60 mg Every 28 Days | Change in Tumor Volume From Screening to End of Study (Week 24) | -0.4 mm^3 | Standard Deviation 21 |
Secondary
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.
Time frame: Week 12 and end of study (Week 24)
Population: Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of assigned study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Octreotide 30 mg Every 21 Days | Percentage of Participants Asymptomatic for Acromegaly Symptoms at Week 12 and End of Study (Week 24) | Week 12 | 33.3 Percentage of participants |
| Octreotide 30 mg Every 21 Days | Percentage of Participants Asymptomatic for Acromegaly Symptoms at Week 12 and End of Study (Week 24) | Week 24 | 20.0 Percentage of participants |
| Octreotide 60 mg Every 28 Days | Percentage of Participants Asymptomatic for Acromegaly Symptoms at Week 12 and End of Study (Week 24) | Week 12 | 9.09 Percentage of participants |
| Octreotide 60 mg Every 28 Days | Percentage of Participants Asymptomatic for Acromegaly Symptoms at Week 12 and End of Study (Week 24) | Week 24 | 9.09 Percentage of participants |
Secondary
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.
Time frame: Screening to end of study (Week 24)
Population: Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of assigned study medication and who had data for this outcome measure.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Octreotide 30 mg Every 21 Days | Percentage of Participants With > 20% Tumor Shrinkage From Screening to End of Study (Week 24) | 14.3 Percentage of participants | 6426 |
| Octreotide 60 mg Every 28 Days | Percentage of Participants With > 20% Tumor Shrinkage From Screening to End of Study (Week 24) | 11.1 Percentage of participants | 4211 |