Efficacy/Safety of Octreotide Acetate in Patients With Uncontrolled Acromegaly

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00372697
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acromegaly	Drug: Octreotide acetate 30 mg suspension	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Octreotide 30 mg every 21 days 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; 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.; Other Names: Sandostatin LAR
Experimental: Octreotide 60 mg every 28 days 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; 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.; Other Names: Sandostatin LAR

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Brescia		Italy

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Chair: Novartis, Novartis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00372697
• Other Study ID Numbers: CSMS995BIT12
• First Posted: Sep 7, 2006
• Last Update Posted: May 17, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: acromegaly; octreotide acetate; partial responder patients
• Additional relevant MeSH terms: Acromegaly; Octreotide

Study Results

Participant Flow

Arm/Group Title	Octreotide 30 mg Every 21 Days	Octreotide 60 mg Every 28 Days
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	16	12
COMPLETED	15	11
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Octreotide 30 mg Every 21 Days	Octreotide 60 mg Every 28 Days	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	16	12	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.3 (12.1)	51.8 (15.7)	51.5 (13.9)
Sex: Female, Male (Count of Participants)
Female	10 62.5%	4 33.3%	14 50%
Male	6 37.5%	8 66.7%	14 50%

Outcome Measures

1. Primary Outcome

Title	Change in Growth Hormone (GH) Level From Screening to End of Study (Week 24)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Octreotide 30 mg Every 21 Days	Octreotide 60 mg Every 28 Days
Arm/Group Description	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.	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.
Measure Participants	15	11
Mean (Standard Deviation) [µg/L]	-1.7 (9.9)	-2.1 (3.6)

2. Primary Outcome

Title	Change in Insulin-like Growth Factor 1 (IGF-1) Level From Screening to End of Study (Week 24)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Octreotide 30 mg Every 21 Days	Octreotide 60 mg Every 28 Days
Arm/Group Description	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.	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.
Measure Participants	15	11
Mean (Standard Deviation) [µg/L]	-40.4 (180.2)	-135.0 (170.9)

3. Secondary Outcome

Title	Change in Tumor Volume From Screening to End of Study (Week 24)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Octreotide 30 mg Every 21 Days	Octreotide 60 mg Every 28 Days
Arm/Group Description	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.	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.
Measure Participants	14	9
Mean (Standard Deviation) [mm^3]	15.9 (91.8)	-0.4 (21.0)

4. Secondary Outcome

Title	Percentage of Participants With > 20% Tumor Shrinkage From Screening to End of Study (Week 24)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Octreotide 30 mg Every 21 Days	Octreotide 60 mg Every 28 Days
Arm/Group Description	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.	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.
Measure Participants	14	9
Number [Percentage of participants]	14.3 (6426) 89.4%	11.1 (4211) 92.5%

5. Secondary Outcome

Title	Percentage of Participants Asymptomatic for Acromegaly Symptoms at Week 12 and End of Study (Week 24)
Description	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)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of assigned study medication.

Arm/Group Title	Octreotide 30 mg Every 21 Days	Octreotide 60 mg Every 28 Days
Arm/Group Description	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.	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.
Measure Participants	15	11
Week 12	33.3 208.1%	9.09 75.8%
Week 24	20.0 125%	9.09 75.8%

6. Secondary Outcome

Title	Acromegaly Quality of Life (AcroQoL) Questionnaire Physical Scale Score at End of Study (Week 24)
Description	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)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of assigned study medication.

Arm/Group Title	Octreotide 30 mg Every 21 Days	Octreotide 60 mg Every 28 Days
Arm/Group Description	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.	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.
Measure Participants	15	11
Mean (Standard Deviation) [Percent of maximum score]	67.9 (22.6)	58.0 (21.8)

7. Secondary Outcome

Title	Acromegaly Quality of Life (AcroQoL) Questionnaire Psychological Scale Score at End of Study (Week 24)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Octreotide 30 mg Every 21 Days	Octreotide 60 mg Every 28 Days
Arm/Group Description	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.	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.
Measure Participants	15	10
Mean (Standard Deviation) [Percent of maximum score]	65.1 (19.9)	72.1 (19.6)

Adverse Events

Arm/Group Title	Octreotide 30 mg Every 21 Days		Octreotide 60 mg Every 28 Days
Arm/Group Description	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.		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.
All Cause Mortality
	Octreotide 30 mg Every 21 Days		Octreotide 60 mg Every 28 Days
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Octreotide 30 mg Every 21 Days		Octreotide 60 mg Every 28 Days
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Octreotide 30 mg Every 21 Days		Octreotide 60 mg Every 28 Days
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/16 (18.8%)		2/12 (16.7%)
Gastrointestinal disorders
Diarrhoea	1/16 (6.3%)	1	2/12 (16.7%)	2
Flatulence	2/16 (12.5%)	2	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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 (ie, data from all sites) in the clinical trial.