Acromegaly
Conditions
Keywords
Acromegaly, Octreotide LAR, Ultrasound guidance
Brief summary
Approximately half of patients with acromegaly do not respond to treatment with somatostatin receptor ligands such as octreotide LAR. This may be due to inadequate drug delivery if the standard of care regular injection is inaccurately delivered in the intramuscular (IM) compartment. Ultrasound guidance of IM injections may improve accuracy of placement of IM injections and increase drug levels, thereby improving efficacy of octreotide LAR for the treatment of acromegaly. The purpose of this study is to determine whether octreotide LAR drug levels differ if given by ultrasound-guided IM injection or by regular IM injection in patients with acromegaly.
Interventions
DRUGOctreotide LAR 30 MG Injection
Stable dose of 30 mg octreotide LAR, or a dose determined by historical dosing, delivered every 28 days for 3 months.
Sponsors
Novartis Pharmaceuticals
Cedars-Sinai Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of active acromegaly based on evidence of a pituitary tumor * Historical serum insulin-like growth factor (IGF)-I levels or a lack of suppression of growth hormone (GH) \< 1 ng/mL during an oral glucose tolerance test * Previous treatment with a stable dose of octreotide LAR for at least 3 months * No previous treatment with a stable dose of octreotide LAR for at least 3 months after receiving 3 months of octreotide LAR during a run-in phase prior to any other study-related activity
Exclusion criteria
* Uncontrolled diabetes mellitus * Pregnant or breast feeding * Current gallstones * History of hepatic disease, except patients with \< 3 X ULN LFTs indicative of hepatic steatosis * Past or current history of cancer, except for basal cell carcinoma or in situ cancer of the cervix * History of glucocorticoid therapy within the past 6 months, current treatment with any chemotherapeutic agents or exogenous GH therapy * History of investigational drugs administered or received within 30 days of study entry * Known hypersensitivity to octreotide LAR * Any other concomitant illnesses or therapy that would interfere with evaluation of efficacy or safety or increase the risk for study interruption or discontinuation in the opinion of the investigator or sponsor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Octreotide Level After Each Treatment Phase | 3 months | Venous sampling was performed at each visit immediately prior to each IM injection. Levels were measured at each visit and mean for the group was calculated after each treatment phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum IGF-1 Level | 3 months | Venous sampling was performed at each visit immediately prior to each IM injection. Levels were measured at each visit and mean for the group was calculated after each treatment phase. |
Countries
United States
Participant flow
Recruitment details
This study recruited subjects with active acromegaly. Equal numbers of men and women were to be recruited, but the recruitment plan was adjusted during the course of the trial to account for the high number of women withdrawn from the study. 12 women and 9 men were recruited; 8 men and 7 women completed the study and were included in the analysis.
Pre-assignment details
Subjects who had not received 3 monthly injections of a stable dose of octreotide LAR prior to enrollment were given 3 monthly injections of octreotide LAR at a stable dose of 30 mg every 28 days or at a dose determined by historical dosing. Nine of the 15 subjects participated in this run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Ultrasound-guided Injections Followed by Regular Injections Subjects received octreotide LAR via ultrasound-guided IM gluteal injections every 28 days for 3 months followed by regular IM gluteal injections every 28 days for 3 months. | 6 |
| Regular Injections Followed by Ultrasound-guided Injections Subjects received octreotide LAR via regular IM gluteal injections every 28 days for 3 months followed by ultrasound-guided IM gluteal injections every 28 days for 3 months. | 9 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Regular Injections Followed by Ultrasound-guided Injections | Ultrasound-guided Injections Followed by Regular Injections | Total |
|---|---|---|---|
| Age, Continuous | 53 years STANDARD_DEVIATION 16 | 56 years STANDARD_DEVIATION 14 | 53 years STANDARD_DEVIATION 15 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 9 participants | 6 participants | 15 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 1 / 11 |
| other Total, other adverse events | 0 / 10 | 1 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 |
Outcome results
Primary
Plasma Octreotide Level After Each Treatment Phase
Venous sampling was performed at each visit immediately prior to each IM injection. Levels were measured at each visit and mean for the group was calculated after each treatment phase.
Time frame: 3 months
Population: Subjects were regrouped for analysis by treatment. Octreotide levels after 3 monthly octreotide LAR injections with ultrasound guidance were compared to octreotide levels obtained after 3 monthly octreotide LAR injection without ultrasound guidance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ultrasound-guided Injections of Octreotide LAR | Plasma Octreotide Level After Each Treatment Phase | 885 pg/mL | Standard Deviation 702 |
| Regular Injections of Octreotide LAR | Plasma Octreotide Level After Each Treatment Phase | 1167 pg/mL | Standard Deviation 1126 |
p-value: 0.4t-test, 2 sided
Secondary
Serum IGF-1 Level
Venous sampling was performed at each visit immediately prior to each IM injection. Levels were measured at each visit and mean for the group was calculated after each treatment phase.
Time frame: 3 months
Population: Subjects were regrouped for analysis by treatment. Serum IGF-I levels after 3 monthly octreotide LAR injections with ultrasound guidance were compared to Serum IGF-I levels obtained after 3 monthly octreotide LAR injection without ultrasound guidance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ultrasound-guided Injections of Octreotide LAR | Serum IGF-1 Level | 132 percentage of upper limit of normal | Standard Deviation 92 |
| Regular Injections of Octreotide LAR | Serum IGF-1 Level | 124 percentage of upper limit of normal | Standard Deviation 83 |
p-value: 0.43t-test, 2 sided