Acromegaly
Conditions
Keywords
Sandostatin LAR, High Dose, GH-receptor antagonist, combination with dopamine-agonist, acromegalic patients, octreotide acetate, Somavert, Dostinex, pegvisomant, cabergoline, not adequately controlled, active acromegaly
Brief summary
This study will assess the efficacy of 8 months treatment of Sandostatin® LAR® High Dose monotherapy or Sandostatin® LAR® High Dose in combination either with growth hormone antagonist or dopamine agonist to control biochemical parameters (GH and insulin-like growth factor I \[IGF I\]) of acromegalic patients not achieving biochemical normalization at conventional regimen.
Interventions
DRUGSandostatin LAR
40 mg intramuscular (i.m.) every 28 days for 3 months
DRUGpegvisomant
Weekly doses of pegvisomant 70 mg subcutaneously (s.c.) for 4 months given with Sandostatin LAR 40 mg intramuscular (i.m.) every 28 days for 4 months
DRUGcabergoline
Weekly cabergoline for 4 months, with weekly doses of Sandostatin LAR 40 mg intramuscular (i.m.) every 28 days for 4 months. Cabergoline doses as follows: 1. st week: 0.25 mg twice a week (0.50 mg/week) 2. nd week: 0.50 mg/week twice a week (1 mg/week) 3. rd week: 0.50 mg four times a week (2 mg/week) 4. th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Patient with a biochemically documented active acromegaly, not adequately controlled by somatostatin-analogues at conventional regimen as follow : mean 1-hour GH \> 2.5 ng/mL and elevated IGF-1 (adjusted for age and gender) * Patient with reduction of either mean fasting GH at least 50% or IGF-1 at least 25% from any medical pretreatment level * Patient currently receiving somatostatin-analogues at conventional regimen (maximum registered dose) for at least 6 months before inclusion
Exclusion criteria
* Newly diagnosed or previously medically untreated acromegalic patient * Concomitant treatment with GH-receptor antagonist * Concomitant treatment with dopamine-agonist * Symptomatic cholelithiasis or choledocolithiasis * Liver transaminases (ALT, AST) elevated, but \> 3 times upper normal limit (according to local laboratory) * Previous gamma-knife radiotherapy for treatment of acromegaly * Compression of the optic chiasm causing visual field defect * Any medical conditions contraindicated in the Summary of Product Characteristic (SPC) of all drugs Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With Complete Response (CR) at 8 Months | From Baseline to 8 months | A patient was classified as a Complete Responder (CR) if both biochemical parameters were controlled at the end of 8 months of treatment: * Mean 1 hour GH \< 2.5µg/L (according to Central Laboratory); and * IGF-I within the Central Laboratory Normal Range (for age and gender). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With Complete Response (CR) At 3 Months | From Baseline to 3 months | A patient was classified as CR if both biochemical parameters were controlled at the end of 3 months of treatment: * Mean 1 hour GH \< 2.5µg/L (according to Central Laboratory); and * IGF-I within the Central Laboratory Normal Range (for age and gender) |
| The Percentage of Participants With Partial Response (PR) at 8 Months | From Baseline to 8 months | Patients who met one of the following criteria at the end of 8 months of treatment were defined as Partial Responders, regardless of the treatment. * Mean 1 hour GH \> 2.5 µg/L and \< 5 µg/L and either a decrease in IGF-I of at least 50% compared to baseline or IGF-I within normal range. * Mean 1 hour GH \< 2.5 µg/L and a decrease in IGF-I of at least 50% compared to baseline and IGF-I outside normal range. |
Countries
France, Italy, Poland, Portugal, Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sandostatin LAR High Dose Alone All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with controlled GH and IGF-I after 3 months of Sandostatin LAR monotherapy continued to receive Sandostatin LAR 40 mg i.m. every 28 days for an additional 4 months. | 7 |
| Sandostatin LAR High Dose + Pegvisomat All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Pegvisomant 70 mg subcutaneously (s.c.) for a further 4 months. | 31 |
| Sandostatin LAR High Dose + Cabergoline All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Cabergoline for a further 4 months, with Cabergoline doses as follows:
* 1st week: 0.25 mg twice a week (0.50 mg/week)
* 2nd week: 0.50 mg/week twice a week (1 mg/week)
* 3rd week: 0.50 mg four times a week (2 mg/week)
* 4th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week) | 32 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative problems | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Other | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Sandostatin LAR High Dose Alone | Sandostatin LAR High Dose + Pegvisomat | Sandostatin LAR High Dose + Cabergoline | Total |
|---|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 7.71 | 44.6 years STANDARD_DEVIATION 10.54 | 49.3 years STANDARD_DEVIATION 10.5 | 48.1 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 3 Participants | 17 Participants | 18 Participants | 38 Participants |
| Sex: Female, Male Male | 4 Participants | 14 Participants | 14 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 7 | 15 / 32 | 12 / 31 |
| serious Total, serious adverse events | 0 / 7 | 1 / 32 | 2 / 31 |
Outcome results
Primary
The Percentage of Participants With Complete Response (CR) at 8 Months
A patient was classified as a Complete Responder (CR) if both biochemical parameters were controlled at the end of 8 months of treatment: * Mean 1 hour GH \< 2.5µg/L (according to Central Laboratory); and * IGF-I within the Central Laboratory Normal Range (for age and gender).
Time frame: From Baseline to 8 months
Population: Intent-to-Treat population - all participants receiving at least one dose of Sandostatin LAR
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sandostatin LAR High Dose Alone | The Percentage of Participants With Complete Response (CR) at 8 Months | 25 percent |
| Sandostatin LAR High Dose + Pegvisomat | The Percentage of Participants With Complete Response (CR) at 8 Months | 0 percent |
| Sandostatin LAR High Dose + Cabergoline | The Percentage of Participants With Complete Response (CR) at 8 Months | 9.4 percent |
Secondary
The Percentage of Participants With Complete Response (CR) At 3 Months
A patient was classified as CR if both biochemical parameters were controlled at the end of 3 months of treatment: * Mean 1 hour GH \< 2.5µg/L (according to Central Laboratory); and * IGF-I within the Central Laboratory Normal Range (for age and gender)
Time frame: From Baseline to 3 months
Population: Intent-to-Treat population - all participants receiving at least one dose of Sandostatin LAR
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sandostatin LAR High Dose Alone | The Percentage of Participants With Complete Response (CR) At 3 Months | 60 percent |
| Sandostatin LAR High Dose + Pegvisomat | The Percentage of Participants With Complete Response (CR) At 3 Months | 0 percent |
| Sandostatin LAR High Dose + Cabergoline | The Percentage of Participants With Complete Response (CR) At 3 Months | 0 percent |
Secondary
The Percentage of Participants With Partial Response (PR) at 8 Months
Patients who met one of the following criteria at the end of 8 months of treatment were defined as Partial Responders, regardless of the treatment. * Mean 1 hour GH \> 2.5 µg/L and \< 5 µg/L and either a decrease in IGF-I of at least 50% compared to baseline or IGF-I within normal range. * Mean 1 hour GH \< 2.5 µg/L and a decrease in IGF-I of at least 50% compared to baseline and IGF-I outside normal range.
Time frame: From Baseline to 8 months
Population: Intent-to-Treat population - all participants receiving at least one dose of Sandostatin LAR
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sandostatin LAR High Dose Alone | The Percentage of Participants With Partial Response (PR) at 8 Months | 25 percent |
| Sandostatin LAR High Dose + Pegvisomat | The Percentage of Participants With Partial Response (PR) at 8 Months | 22.6 percent |
| Sandostatin LAR High Dose + Cabergoline | The Percentage of Participants With Partial Response (PR) at 8 Months | 21.9 percent |