Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Sandostatin LAR at High Dose or in Combination Either With GH-receptor Antagonist or Dopamine-agonist in Acromegalic Patients (NCT NCT01278342)
NCT ID: NCT01278342
Last Updated: 2017-03-03
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
70 participants
Primary outcome timeframe
From Baseline to 8 months
Results posted on
2017-03-03
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
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)
|
|---|---|---|---|
|
Overall Study
STARTED
|
7
|
31
|
32
|
|
Overall Study
COMPLETED
|
3
|
30
|
32
|
|
Overall Study
NOT COMPLETED
|
4
|
1
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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)
|
|---|---|---|---|
|
Overall Study
Physician Decision
|
0
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
|
Overall Study
Administrative problems
|
2
|
0
|
0
|
|
Overall Study
Other
|
1
|
0
|
0
|
Baseline Characteristics
Study to Evaluate the Efficacy and Safety of Sandostatin LAR at High Dose or in Combination Either With GH-receptor Antagonist or Dopamine-agonist in Acromegalic Patients
Baseline characteristics by cohort
| Measure |
Sandostatin LAR High Dose Alone
n=7 Participants
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.
|
Sandostatin LAR High Dose + Pegvisomat
n=31 Participants
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.
|
Sandostatin LAR High Dose + Cabergoline
n=32 Participants
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)
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57.9 years
STANDARD_DEVIATION 7.71 • n=99 Participants
|
44.6 years
STANDARD_DEVIATION 10.54 • n=107 Participants
|
49.3 years
STANDARD_DEVIATION 10.50 • n=206 Participants
|
48.1 years
STANDARD_DEVIATION 10.90 • n=7 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
38 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
32 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: From Baseline to 8 monthsPopulation: Intent-to-Treat population - all participants receiving at least one dose of Sandostatin LAR
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).
Outcome measures
| Measure |
Sandostatin LAR High Dose Alone
n=7 Participants
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.
|
Sandostatin LAR High Dose + Pegvisomat
n=31 Participants
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.
|
Sandostatin LAR High Dose + Cabergoline
n=32 Participants
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)
|
|---|---|---|---|
|
The Percentage of Participants With Complete Response (CR) at 8 Months
|
25 percent
Interval 0.6 to 80.6
|
0 percent
Interval 0.0 to 11.2
|
9.4 percent
Interval 2.0 to 25.0
|
SECONDARY outcome
Timeframe: From Baseline to 3 monthsPopulation: Intent-to-Treat population - all participants receiving at least one dose of Sandostatin LAR
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)
Outcome measures
| Measure |
Sandostatin LAR High Dose Alone
n=7 Participants
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.
|
Sandostatin LAR High Dose + Pegvisomat
n=31 Participants
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.
|
Sandostatin LAR High Dose + Cabergoline
n=32 Participants
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)
|
|---|---|---|---|
|
The Percentage of Participants With Complete Response (CR) At 3 Months
|
60 percent
Interval 14.7 to 94.7
|
0 percent
Interval 0.0 to 11.2
|
0 percent
Interval 0.0 to 10.9
|
SECONDARY outcome
Timeframe: From Baseline to 8 monthsPopulation: Intent-to-Treat population - all participants receiving at least one dose of Sandostatin LAR
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.
Outcome measures
| Measure |
Sandostatin LAR High Dose Alone
n=7 Participants
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.
|
Sandostatin LAR High Dose + Pegvisomat
n=31 Participants
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.
|
Sandostatin LAR High Dose + Cabergoline
n=32 Participants
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)
|
|---|---|---|---|
|
The Percentage of Participants With Partial Response (PR) at 8 Months
|
25 percent
Interval 0.6 to 80.6
|
22.6 percent
Interval 9.6 to 41.1
|
21.9 percent
Interval 9.3 to 40.0
|
Adverse Events
Sandostatin LAR High Dose + Pegvisomant
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Sandostatin LAR High Dose + Cabergoline
Serious events: 2 serious events
Other events: 12 other events
Deaths: 0 deaths
Sandostatin LAR High Dose Alone
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sandostatin LAR High Dose + Pegvisomant
n=32 participants at risk
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.
|
Sandostatin LAR High Dose + Cabergoline
n=31 participants at risk
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)
|
Sandostatin LAR High Dose Alone
n=7 participants at risk
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
|
|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.00%
0/32
|
3.2%
1/31
|
0.00%
0/7
|
|
Nervous system disorders
IIIrd nerve paralysis
|
0.00%
0/32
|
3.2%
1/31
|
0.00%
0/7
|
|
Vascular disorders
Deep vein thrombosis
|
3.1%
1/32
|
0.00%
0/31
|
0.00%
0/7
|
Other adverse events
| Measure |
Sandostatin LAR High Dose + Pegvisomant
n=32 participants at risk
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.
|
Sandostatin LAR High Dose + Cabergoline
n=31 participants at risk
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)
|
Sandostatin LAR High Dose Alone
n=7 participants at risk
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
|
|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
3.1%
1/32
|
6.5%
2/31
|
0.00%
0/7
|
|
Gastrointestinal disorders
Abdominal pain
|
6.2%
2/32
|
9.7%
3/31
|
0.00%
0/7
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
4/32
|
9.7%
3/31
|
0.00%
0/7
|
|
Gastrointestinal disorders
Dyspepsia
|
6.2%
2/32
|
0.00%
0/31
|
0.00%
0/7
|
|
Gastrointestinal disorders
Flatulence
|
6.2%
2/32
|
0.00%
0/31
|
0.00%
0/7
|
|
Infections and infestations
Nasopharyngitis
|
6.2%
2/32
|
3.2%
1/31
|
14.3%
1/7
|
|
Infections and infestations
Pneumonia
|
0.00%
0/32
|
0.00%
0/31
|
14.3%
1/7
|
|
Investigations
Blood glucose increased
|
12.5%
4/32
|
0.00%
0/31
|
0.00%
0/7
|
|
Investigations
Blood insulin decreased
|
0.00%
0/32
|
0.00%
0/31
|
14.3%
1/7
|
|
Investigations
Glycosylated haemoglobin increased
|
6.2%
2/32
|
0.00%
0/31
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
6.2%
2/32
|
3.2%
1/31
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/32
|
9.7%
3/31
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.1%
1/32
|
9.7%
3/31
|
0.00%
0/7
|
|
Nervous system disorders
Aphonia
|
0.00%
0/32
|
0.00%
0/31
|
14.3%
1/7
|
|
Nervous system disorders
Headache
|
0.00%
0/32
|
12.9%
4/31
|
0.00%
0/7
|
|
Renal and urinary disorders
Calculus bladder
|
0.00%
0/32
|
0.00%
0/31
|
14.3%
1/7
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER