Acromegaly
Conditions
Keywords
Acromegaly,, adult,, growth hormone,, insulin-like growth factor I,, somatostatin analogue
Brief summary
The patients received either Pasireotide LAR or Octreotide LAR for one year of treatment. The objective of this study was to compare the proportion of patients with a reduction of mean GH level to \<2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) between the two treatment groups (pasireotide LAR and octreotide LAR) at 12 months. Following one year of treatment patients could proceed into the study extension. Patients who did not respond to the treatment they were randomized to (based on month 12 assessment results) were switched to the other treatment arm at month 13.
Interventions
DRUGPasireotide
Pasireotide LAR - intramuscular (i.m.) depot injection given once every 28 days.
DRUGOctreotide
Octreotide LAR - i.m. depot injection given once every 28 days.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with active acromegaly (based on elevated GH and IGF-1 levels) * Patients who have undergone one or more pituitary surgeries, but have not been treated medically, or de-novo patients presenting a visible pituitary adenoma on MRI and who refuse pituitary surgery or for whom pituitary surgery is contraindicated * Patients for whom written informed consent to participate in the study has been obtained prior to any study related activity
Exclusion criteria
* Patients who are being or were treated with octreotide, lanreotide, dopamine agonists or GH antagonists with the exception of a single dose of short-acting octrotide or short-acting dopamine agonists. In case of a single dose of short-acting octrotide, the dose should not be used to predict the response to the octretide treatment. The single dose of short-acting octreotide or short-acting dopamine agonists should not be administered in the 3 days prior to randomization * Patients with compression of the optic chiasm causing any visual field defect * Patients who have received pituitary irradiation within the last ten years prior to visit 1 * Poorly controlled diabetic patients Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 | 12 months | Percentage of participants with a reduction of mean GH levels to \<2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Tumor Volume at 12 Months | Baseline, 12 Months | Absolute and percentage change from baseline in tumor volume (assessed by pituitary MRI) Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated. |
| Percentage of Participants With Normalization of IGF-1 | 12 Months | Percentage of participants with normalization of sex- and age-adjusted IGF-1. Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated. |
| Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Months 3, 6, 9, 12, 16, 19, 22, 25 | Percentage of participants with a reduction of mean GH levels to \< 2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Denominator for time points up to Month 12 is the Full Analysis Set (FAS). Denominator for time points after Month 12 excludes patients who completed the core and did not enter the extension. Patients who discontinued were considered non-responders for the time points after discontinuation, patients who crossed over were considered non-responders for all time points after crossover. Analysis was based on data up to crossover (i.e., included data from both blinded core & ext. phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included.) |
| Summary of Mean GH Values | Baseline, Months 3, 6, 9, 12, 16, 19, 22, 25 | Mean GH levels (based on a 5-point profile over 2 hours). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). |
| Time to First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 (No. of Responders: Pasireotite LAR = 81, Octreotide LAR = 63) ) | Up to 26 months | Time to first response for patients achieving a reduction of mean GH level to \< 2.5 μg/L and normalization of IGF-1. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). |
| Severity Scores of Acromegaly Symptoms | Baseline, Months 12, 25 | Severity scores of acromegaly symptoms (Headache, Fatigue, Perspiration, Paresthesias, Osteoarthralgia). Symptoms were scored from 0 (no symptom) to 4 (very severe). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). |
| Ring Size | Baseline, Months 12, 25 | Ring size (based on jeweler's finger gauge). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). |
| Health-related Quality-of-life as Measured by the AcroQoL Questionnaire | Baseline, Months 12, 25 | Acromegalyy quality of life (AcroQoL) total scores. The AcroQoL questionnaire is unidimensional and contains 22 items divided in two scales: one that evaluates physical aspects (eight items) and another one that evaluates psychological aspects (14 items). The scoring of the questionnaire was performed as specified by the instrument developers. Total scores range from 0 to 100. Higher scores represent better quality of life. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). |
| Summary of Prolactin Levels | Baseline, Months 12, 25 | Prolactin Levels. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). |
| Duration of Response for Patients Achieving a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 at Month 12 (No. of Responders: Pasireotide LAR = 51, Octreotide LAR = 32) | Up to 26 months | The duration of response is defined as the time from the date that patient first met and maintained the response criteria based on primary efficacy variable to the date that patient lost response status. Median and corresponding 95% CI are derived based on Kaplan-Meier method. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). |
| Pasireotide Trough Concentrations by Incident Dose | Months 1 - 12 | Pasireotide LAR trough concentrations by incident dose (last dose administered prior to PK sample collection). PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28±2 days window were excluded. 5 patients with evaluable PK data in the pasireotide arm received erroneously 20 mg pasireotide LAR at baseline. |
| Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | 12 Months | Percentage of participants with a reduction of mean GH levels to \< 2.5μg/L (based on a 5-point 2-hour profile). Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated. |
| Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover | Months 3, 6, 9, 12 after crossover | Percentage of participants with a reduction of mean GH levels to \< 2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Denominator for all time points is the Crossover Analysis Set (CAS). |
| Change From Baseline in Tumor Volume | Baseline, months 6, 12, 19, 25 | Percentage change from baseline in tumor volume (assessed by pituitary MRI). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). |
| Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover | Months 3, 6, 9, 12 after crossover | Percentage of participants with a reduction of mean GH levels to \< 2.5μg/L (based on a 5-point 2-hour profile). Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Denominator for all time points is the Crossover Analysis Set (CAS). |
| Percentage of Participants With Normalization of IGF-1 After Crossover | Months 3, 6, 9, 12 after crossover | Percentage of participants with normalization of sex- and age-adjusted IGF-1. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Denominator for all time points is the Crossover Analysis Set (CAS). |
| Summary of Mean GH Values After Crossover | Extension baseline, months 3, 6, 9, 12 after crossover | Mean GH levels (based on a 5-point profile over 2 hours). Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). |
| Change From Extension Baseline in Tumor Volume After Crossover | Extension baseline, months 6, 12 after crossover | Percentage change from extension baseline in tumor volume (assessed by pituitary MRI). Extension baseline was defined as last assessment prior to the administration of the new treatment after crossover. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). |
| Severity Scores of Acromegaly Symptoms After Crossover | Extension baseline, month 12 after crossover | Severity scores of acromegaly symptoms (Headache, Fatigue, Perspiration, Paresthesias, Osteoarthralgia). Symptoms were scored from 0 (no symptom) to 4 (very severe). Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). |
| Ring Size After Crossover | Extension baseline, month 12 after crossover | Ring size (based on jeweler's finger gauge). Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). BL = baseline, LH = left hand, RH = right hand, CO = crossover |
| Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover | Extension baseline, months 12 after crossover | AcroQoL total scores. The AcroQoL questionnaire is unidimensional and contains 22 items divided in two scales: one that evaluates physical aspects (eight items) and another one that evaluates psychological aspects (14 items). The scoring of the questionnaire was performed as specified by the instrument developers. Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Total scores range from 0 to 100. Higher scores represent better quality of life. |
| Summary of Prolactin Levels After Crossover | Extension baseline, month 12 after crossover | Prolactin (PRL) levels. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Extension baseline was defined as last measurement prior to the start of crossover treatment. |
| Octreotide Trough Concentrations by Incident Dose | Months 1 - 12 | Octreotide LAR trough concentrations by incident dose (last dose administered prior to PK sample collection). PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28±2 days window were excluded. |
Countries
Argentina, Belgium, Brazil, Canada, China, Colombia, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Mexico, Netherlands, Norway, Poland, Russia, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pasireotide LAR Patients in this arm received Pasireotide LAR 40 mg im depot injection, blinded, once every 28 days (± 2 days) for 12 months. Dose could be down- or up-titrated to 20 or 60 mg, respectively. Patients who responded to Pasireotide LAR (i.e. the randomized treatment) at the end of the core (Month 12), continued Pasireotide LAR treatment in the extension. Patients who did not respond to Pasireotide LAR at the end of the core (Month 12) were allowed to switch to receive Octreotide LAR in the extension. | 176 |
| Octreotide LAR Patients in this arm received Octreotide LAR 20 mg im depot injection, blinded, once every 28 days (± 2 days) for 12 months. Dose could be down- or up-titrated to 10 or 30 mg, respectively. Patients who responded to Octreotide LAR (i.e. the randomized treatment) at the end of the core (Month 12) continued Octreotide LAR treatment in the extension (up to 2 years of treatment). Patients who did not respond to Octreotide LAR at the end of the core (Month 12) were allowed to switch to receive Pasireotide LAR in the extension. | 182 |
| Total | 358 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core Phase - Full Analysis Set (FAS) | Abnormal laboratory value(s) | 1 | 0 |
| Core Phase - Full Analysis Set (FAS) | Administrative Problems | 2 | 0 |
| Core Phase - Full Analysis Set (FAS) | Adverse Event | 14 | 6 |
| Core Phase - Full Analysis Set (FAS) | Death | 0 | 1 |
| Core Phase - Full Analysis Set (FAS) | Lack of Efficacy | 5 | 8 |
| Core Phase - Full Analysis Set (FAS) | Lost to Follow-up | 1 | 0 |
| Core Phase - Full Analysis Set (FAS) | Protocol Violation | 7 | 8 |
| Core Phase - Full Analysis Set (FAS) | Withdrawal by Subject | 5 | 3 |
| Extension - After Crossover (CAS) | Abnormal Lab Value (s) | 3 | 0 |
| Extension - After Crossover (CAS) | Administrative Problems | 4 | 4 |
| Extension - After Crossover (CAS) | Adverse Event | 19 | 1 |
| Extension - After Crossover (CAS) | Death | 1 | 0 |
| Extension - After Crossover (CAS) | Lack of Efficacy | 13 | 4 |
| Extension - After Crossover (CAS) | Subject no longer requires study drug | 3 | 0 |
| Extension - After Crossover (CAS) | Withdrawal by Subject | 19 | 4 |
| Extension - Same Treatment (FAS) | Abnormal Lab Value (s) | 4 | 0 |
| Extension - Same Treatment (FAS) | Administrative Problems | 9 | 3 |
| Extension - Same Treatment (FAS) | Adverse Event | 4 | 1 |
| Extension - Same Treatment (FAS) | Condition no longer requires study drug | 6 | 0 |
| Extension - Same Treatment (FAS) | Death | 1 | 1 |
| Extension - Same Treatment (FAS) | Lack of Efficacy | 3 | 3 |
| Extension - Same Treatment (FAS) | Lost to Follow-up | 3 | 1 |
| Extension - Same Treatment (FAS) | Withdrawal by Subject | 16 | 2 |
Baseline characteristics
| Characteristic | Pasireotide LAR | Octreotide LAR | Total |
|---|---|---|---|
| Age, Continuous | 45.1 Years STANDARD_DEVIATION 12.37 | 45.6 Years STANDARD_DEVIATION 12.97 | 45.4 Years STANDARD_DEVIATION 12.67 |
| Age, Customized >=65 years | 8 Participants | 15 Participants | 23 Participants |
| Age, Customized <65 Years | 168 Participants | 167 Participants | 335 Participants |
| Sex: Female, Male Female | 91 Participants | 95 Participants | 186 Participants |
| Sex: Female, Male Male | 85 Participants | 87 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 169 / 178 | 161 / 180 | 74 / 81 | 33 / 38 | 170 / 178 | 76 / 81 |
| serious Total, serious adverse events | 35 / 178 | 28 / 180 | 8 / 81 | 6 / 38 | 37 / 178 | 12 / 81 |
Outcome results
Primary
Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1
Percentage of participants with a reduction of mean GH levels to \<2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
Time frame: 12 months
Population: Full Analysis Set: All patients (Pts) who were randomized into the study. Pts were analyzed according to the treatment they were assigned to at randomization. Missing mean GH and/or IGF-1 levels at M12 were imputed using data obtained at or after M6 by the last observation carried forward method; otherwise, Pts were considered as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 | Overall | 31.3 Percentage of Participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 | Post Surgery | 39.4 Percentage of Participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 | De novo | 25.7 Percentage of Participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 | Overall | 19.2 Percentage of Participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 | Post Surgery | 21.8 Percentage of Participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 | De novo | 17.3 Percentage of Participants |
Comparison: Overall - All patientsp-value: 0.00795% CI: [1.19, 3.168]Cochran-Mantel-Haenszel
Comparison: Post surgery - patients with prior surgery but no previous medical treatment for acromegaly95% CI: [1.14, 4.79]
Comparison: De novo - patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.95% CI: [0.846, 3.234]
Secondary
Change From Baseline in Tumor Volume
Percentage change from baseline in tumor volume (assessed by pituitary MRI). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Time frame: Baseline, months 6, 12, 19, 25
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume | M6 | 1614.1 mm^3 | Standard Deviation 2536.46 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume | % change at M6 | -29.9 mm^3 | Standard Deviation 21.73 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume | M19 | 956.6 mm^3 | Standard Deviation 1806.72 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume | % change at M12 | -39.7 mm^3 | Standard Deviation 21.83 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume | M12 | 1482.4 mm^3 | Standard Deviation 2387.88 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume | % change at M19 | -48.9 mm^3 | Standard Deviation 22.81 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume | M25 | 840.4 mm^3 | Standard Deviation 1706.07 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume | % change at M25 | -51.8 mm^3 | Standard Deviation 20.81 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume | Baseline | 2420.7 mm^3 | Standard Deviation 4159.21 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume | % change at M25 | -55.0 mm^3 | Standard Deviation 21.27 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume | Baseline | 2259.2 mm^3 | Standard Deviation 3390.2 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume | M6 | 1565.4 mm^3 | Standard Deviation 2245.99 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume | M12 | 1390.4 mm^3 | Standard Deviation 2179.93 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume | M19 | 1009.9 mm^3 | Standard Deviation 1578.75 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume | M25 | 814.1 mm^3 | Standard Deviation 1306.58 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume | % change at M6 | -28.8 mm^3 | Standard Deviation 20.22 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume | % change at M12 | -38.0 mm^3 | Standard Deviation 24.47 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume | % change at M19 | -47.2 mm^3 | Standard Deviation 24.08 |
Secondary
Change From Baseline in Tumor Volume at 12 Months
Absolute and percentage change from baseline in tumor volume (assessed by pituitary MRI) Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
Time frame: Baseline, 12 Months
Population: Full Analysis Set (FAS): All patients who were randomized into the study. Patients were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Overall at baseline | 2420.7 mm^3 | Standard Deviation 4159.21 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | De novo % change at month 12 | -39.9 mm^3 | Standard Deviation 22.65 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Post surgery at baseline | 2185.2 mm^3 | Standard Deviation 2861.09 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Overall absolute change at month 12 | -987.1 mm^3 | Standard Deviation 2448.14 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Overall % change at month 12 | -39.7 mm^3 | Standard Deviation 21.83 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Post surgery abs. change at month 12 | -873.7 mm^3 | Standard Deviation 1282.06 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | De novo at baseline | 2592.4 mm^3 | Standard Deviation 4901.99 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | De novo absolute change at month 12 | -1051.9 mm^3 | Standard Deviation 2919.18 |
| Pasireotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Post surgery % change at month 12 | -39.5 mm^3 | Standard Deviation 20.6 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | De novo absolute change at month 12 | -867.1 mm^3 | Standard Deviation 1661.24 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Post surgery % change at month 12 | -39.0 mm^3 | Standard Deviation 23.81 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Overall at baseline | 2259.2 mm^3 | Standard Deviation 3390.2 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Overall % change at month 12 | -38.0 mm^3 | Standard Deviation 24.47 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Post surgery at baseline | 2196.5 mm^3 | Standard Deviation 3922.08 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | De novo at baseline | 2308.1 mm^3 | Standard Deviation 2930.84 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | De novo % change at month 12 | -37.2 mm^3 | Standard Deviation 25.07 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Overall absolute change at month 12 | -801.2 mm^3 | Standard Deviation 1676.62 |
| Octreotide LAR (Core) | Change From Baseline in Tumor Volume at 12 Months | Post surgery abs. change at month 12 | -713.8 mm^3 | Standard Deviation 1708.2 |
Secondary
Change From Extension Baseline in Tumor Volume After Crossover
Percentage change from extension baseline in tumor volume (assessed by pituitary MRI). Extension baseline was defined as last assessment prior to the administration of the new treatment after crossover. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over).
Time frame: Extension baseline, months 6, 12 after crossover
Population: CAS: All patients whose first dose in the extension is different from the first dose in the core. Patients were analyzed according to the crossover treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | Ext. Baseline | 1420.9 mm^3 | Standard Deviation 1914.58 |
| Pasireotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | % change - M6 after crossover | -18.1 mm^3 | Standard Deviation 17.68 |
| Pasireotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | Value at M6 after crossover | 1027.5 mm^3 | Standard Deviation 1282.42 |
| Pasireotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | Value at M12 after crossover | 949.0 mm^3 | Standard Deviation 1169.49 |
| Pasireotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | % change - M12 after crossover | -24.7 mm^3 | Standard Deviation 25.2 |
| Octreotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | Value at M6 after crossover | 1794.9 mm^3 | Standard Deviation 2823.08 |
| Octreotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | % change - M12 after crossover | -17.9 mm^3 | Standard Deviation 27.8 |
| Octreotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | Ext. Baseline | 1809.6 mm^3 | Standard Deviation 2579.25 |
| Octreotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | Value at M12 after crossover | 1610.4 mm^3 | Standard Deviation 2666.66 |
| Octreotide LAR (Core) | Change From Extension Baseline in Tumor Volume After Crossover | % change - M6 after crossover | -12.3 mm^3 | Standard Deviation 24.11 |
Secondary
Duration of Response for Patients Achieving a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 at Month 12 (No. of Responders: Pasireotide LAR = 51, Octreotide LAR = 32)
The duration of response is defined as the time from the date that patient first met and maintained the response criteria based on primary efficacy variable to the date that patient lost response status. Median and corresponding 95% CI are derived based on Kaplan-Meier method. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Time frame: Up to 26 months
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pasireotide LAR (Core) | Duration of Response for Patients Achieving a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 at Month 12 (No. of Responders: Pasireotide LAR = 51, Octreotide LAR = 32) | 64.4 Weeks |
| Octreotide LAR (Core) | Duration of Response for Patients Achieving a Reduction of Mean GH Level to <2.5 μg/L and the Normalization of IGF-1 at Month 12 (No. of Responders: Pasireotide LAR = 51, Octreotide LAR = 32) | 64.6 Weeks |
Secondary
Health-related Quality-of-life as Measured by the AcroQoL Questionnaire
Acromegalyy quality of life (AcroQoL) total scores. The AcroQoL questionnaire is unidimensional and contains 22 items divided in two scales: one that evaluates physical aspects (eight items) and another one that evaluates psychological aspects (14 items). The scoring of the questionnaire was performed as specified by the instrument developers. Total scores range from 0 to 100. Higher scores represent better quality of life. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Time frame: Baseline, Months 12, 25
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire | Baseline | 58.4 Score on a scale | Standard Deviation 19.97 |
| Pasireotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire | M12 | 65.7 Score on a scale | Standard Deviation 21.64 |
| Pasireotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire | M25 | 69.3 Score on a scale | Standard Deviation 18.76 |
| Octreotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire | Baseline | 55.6 Score on a scale | Standard Deviation 19.79 |
| Octreotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire | M12 | 61.6 Score on a scale | Standard Deviation 21.01 |
| Octreotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire | M25 | 62.9 Score on a scale | Standard Deviation 18.86 |
Secondary
Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover
AcroQoL total scores. The AcroQoL questionnaire is unidimensional and contains 22 items divided in two scales: one that evaluates physical aspects (eight items) and another one that evaluates psychological aspects (14 items). The scoring of the questionnaire was performed as specified by the instrument developers. Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Total scores range from 0 to 100. Higher scores represent better quality of life.
Time frame: Extension baseline, months 12 after crossover
Population: CAS: All patients whose first dose in the extension is different from the first dose in the core. Patients were analyzed according to the crossover treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover | Ext. Baseline | 58.9 scores on a scale | Standard Deviation 23.11 |
| Pasireotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover | M12 after crossover | 60.3 scores on a scale | Standard Deviation 24.34 |
| Octreotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover | Ext. Baseline | 59.8 scores on a scale | Standard Deviation 22.4 |
| Octreotide LAR (Core) | Health-related Quality-of-life as Measured by the AcroQoL Questionnaire After Crossover | M12 after crossover | 61.2 scores on a scale | Standard Deviation 21.62 |
Secondary
Octreotide Trough Concentrations by Incident Dose
Octreotide LAR trough concentrations by incident dose (last dose administered prior to PK sample collection). PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28±2 days window were excluded.
Time frame: Months 1 - 12
Population: PK analysis set: All patients with at least one LAR injection and one post-dose trough concentration data in core phase (up to month 12). No participants took the 30 mg dose in Months 1, 2 and 3, hence no data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M4 | 0.19 ng/mL | — |
| Pasireotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M12 | 0.30 ng/mL | — |
| Pasireotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M7 | 0.70 ng/mL | — |
| Pasireotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M2 | 0.61 ng/mL | Standard Deviation 0.28 |
| Pasireotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M3 | 0.62 ng/mL | Standard Deviation 0.107 |
| Pasireotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M6 | 1.33 ng/mL | Standard Deviation 0.754 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M12 | 1.58 ng/mL | Standard Deviation 0.695 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M5 | 1.65 ng/mL | Standard Deviation 0.876 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M6 | 1.58 ng/mL | Standard Deviation 0.811 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M2 | 1.21 ng/mL | Standard Deviation 0.663 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M7 | 1.46 ng/mL | Standard Deviation 0.704 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M3 | 1.29 ng/mL | Standard Deviation 0.654 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M8 | 1.55 ng/mL | Standard Deviation 0.727 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M9 | 1.74 ng/mL | Standard Deviation 1.013 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M10 | 1.66 ng/mL | Standard Deviation 0.995 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M4 | 1.45 ng/mL | Standard Deviation 0.653 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M11 | 1.74 ng/mL | Standard Deviation 0.89 |
| Octreotide LAR (Core) | Octreotide Trough Concentrations by Incident Dose | M1 | 0.86 ng/mL | Standard Deviation 0.493 |
| Pasireotide LAR 60mg | Octreotide Trough Concentrations by Incident Dose | M12 | 2.55 ng/mL | Standard Deviation 1.252 |
| Pasireotide LAR 60mg | Octreotide Trough Concentrations by Incident Dose | M4 | 1.55 ng/mL | Standard Deviation 0.658 |
| Pasireotide LAR 60mg | Octreotide Trough Concentrations by Incident Dose | M5 | 2.14 ng/mL | Standard Deviation 1.156 |
| Pasireotide LAR 60mg | Octreotide Trough Concentrations by Incident Dose | M6 | 2.12 ng/mL | Standard Deviation 0.99 |
| Pasireotide LAR 60mg | Octreotide Trough Concentrations by Incident Dose | M7 | 2.14 ng/mL | Standard Deviation 1.009 |
| Pasireotide LAR 60mg | Octreotide Trough Concentrations by Incident Dose | M8 | 2.16 ng/mL | Standard Deviation 1.127 |
| Pasireotide LAR 60mg | Octreotide Trough Concentrations by Incident Dose | M9 | 2.20 ng/mL | Standard Deviation 0.992 |
| Pasireotide LAR 60mg | Octreotide Trough Concentrations by Incident Dose | M10 | 2.50 ng/mL | Standard Deviation 1.194 |
| Pasireotide LAR 60mg | Octreotide Trough Concentrations by Incident Dose | M11 | 2.39 ng/mL | Standard Deviation 1.103 |
Secondary
Pasireotide Trough Concentrations by Incident Dose
Pasireotide LAR trough concentrations by incident dose (last dose administered prior to PK sample collection). PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28±2 days window were excluded. 5 patients with evaluable PK data in the pasireotide arm received erroneously 20 mg pasireotide LAR at baseline.
Time frame: Months 1 - 12
Population: PK analysis set: All patients with at least one LAR injection and one post-dose trough concentration data in core phase (up to month 12). No participants took the 60 mg dose in Months 1, 2 and 3, hence no data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M6 | 2.87 ng/mL | Standard Deviation 1.101 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M4 | 3.93 ng/mL | Standard Deviation 1.858 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M10 | 5.66 ng/mL | Standard Deviation 3.606 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M7 | 2.29 ng/mL | Standard Deviation 0.857 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M1 | 4.65 ng/mL | Standard Deviation 0.645 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M9 | 4.80 ng/mL | Standard Deviation 1.957 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M8 | 3.65 ng/mL | Standard Deviation 1.865 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M3 | 3.39 ng/mL | Standard Deviation 2.659 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M12 | 4.54 ng/mL | Standard Deviation 1.634 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M5 | 5.22 ng/mL | Standard Deviation 4.077 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M2 | 2.88 ng/mL | Standard Deviation 1.371 |
| Pasireotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M11 | 5.10 ng/mL | Standard Deviation 2.375 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M7 | 11.85 ng/mL | Standard Deviation 7.781 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M1 | 6.65 ng/mL | Standard Deviation 3.641 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M2 | 7.81 ng/mL | Standard Deviation 3.505 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M3 | 8.70 ng/mL | Standard Deviation 5.402 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M4 | 9.51 ng/mL | Standard Deviation 5.487 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M5 | 10.92 ng/mL | Standard Deviation 6.017 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M6 | 10.59 ng/mL | Standard Deviation 6.216 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M8 | 12.33 ng/mL | Standard Deviation 7.619 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M9 | 12.75 ng/mL | Standard Deviation 8.604 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M10 | 12.42 ng/mL | Standard Deviation 7.252 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M11 | 12.62 ng/mL | Standard Deviation 6.92 |
| Octreotide LAR (Core) | Pasireotide Trough Concentrations by Incident Dose | M12 | 11.11 ng/mL | Standard Deviation 6.489 |
| Pasireotide LAR 60mg | Pasireotide Trough Concentrations by Incident Dose | M6 | 13.08 ng/mL | Standard Deviation 6.967 |
| Pasireotide LAR 60mg | Pasireotide Trough Concentrations by Incident Dose | M4 | 13.48 ng/mL | Standard Deviation 7.75 |
| Pasireotide LAR 60mg | Pasireotide Trough Concentrations by Incident Dose | M10 | 16.01 ng/mL | Standard Deviation 11.497 |
| Pasireotide LAR 60mg | Pasireotide Trough Concentrations by Incident Dose | M5 | 13.42 ng/mL | Standard Deviation 6.902 |
| Pasireotide LAR 60mg | Pasireotide Trough Concentrations by Incident Dose | M12 | 16.16 ng/mL | Standard Deviation 9.323 |
| Pasireotide LAR 60mg | Pasireotide Trough Concentrations by Incident Dose | M8 | 15.88 ng/mL | Standard Deviation 9.073 |
| Pasireotide LAR 60mg | Pasireotide Trough Concentrations by Incident Dose | M7 | 14.76 ng/mL | Standard Deviation 6.868 |
| Pasireotide LAR 60mg | Pasireotide Trough Concentrations by Incident Dose | M11 | 16.31 ng/mL | Standard Deviation 10.596 |
| Pasireotide LAR 60mg | Pasireotide Trough Concentrations by Incident Dose | M9 | 16.03 ng/mL | Standard Deviation 10.852 |
Secondary
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
Percentage of participants with a reduction of mean GH levels to \< 2.5μg/L (based on a 5-point 2-hour profile). Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
Time frame: 12 Months
Population: FAS: All patients (Pts) who were randomized into the study. Pts were analyzed according to the treatment they were assigned to at randomization. Missing mean GH levels at Month 12 were imputed using data obtained at or after Month 6 by the LOCF (last observation carried forward) method; otherwise, Pts were considered as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | Overall | 48.3 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | Post surgery | 52.1 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | De novo | 45.7 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | Overall | 51.6 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | Post surgery | 51.3 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | De novo | 51.9 Percentage of participants |
Secondary
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L
Percentage of participants with a reduction of mean GH levels to \< 2.5μg/L (based on a 5-point 2-hour profile). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). Denominator for time points up to Month 12 is the Full Analysis Set. Denominator for time points after Month 12 excludes patients who completed the core and did not enter the extension. Patients who discontinued were considered non-responders for the time points after discontinuation, patients who crossed over were considered non-responders for all time points after crossover.
Time frame: Months 3, 6, 9, 12, 16, 19, 22, 25
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M3 | 49.4 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M6 | 45.5 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M9 | 42.6 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M12 | 43.2 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M16 | 33.3 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M19 | 36.7 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M22 | 35.4 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M25 | 35.4 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M25 | 24.2 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M3 | 43.4 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M16 | 22.2 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M6 | 47.8 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M22 | 22.2 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M9 | 46.2 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M19 | 21.6 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L | M12 | 47.3 Percentage of participants |
Secondary
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover
Percentage of participants with a reduction of mean GH levels to \< 2.5μg/L (based on a 5-point 2-hour profile). Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Denominator for all time points is the Crossover Analysis Set (CAS).
Time frame: Months 3, 6, 9, 12 after crossover
Population: CAS: All patients whose first dose in the extension is different from the first dose in the core. Patients were analyzed according to the crossover treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover | M3 after crossover | 49.4 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover | M6 after crossover | 43.2 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover | M9 after crossover | 54.3 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover | M12 after crossover | 44.4 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover | M12 after crossover | 23.7 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover | M3 after crossover | 28.9 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover | M9 after crossover | 31.6 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L After Crossover | M6 after crossover | 31.6 Percentage of participants |
Secondary
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1
Percentage of participants with a reduction of mean GH levels to \< 2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Denominator for time points up to Month 12 is the Full Analysis Set (FAS). Denominator for time points after Month 12 excludes patients who completed the core and did not enter the extension. Patients who discontinued were considered non-responders for the time points after discontinuation, patients who crossed over were considered non-responders for all time points after crossover. Analysis was based on data up to crossover (i.e., included data from both blinded core & ext. phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included.)
Time frame: Months 3, 6, 9, 12, 16, 19, 22, 25
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 3 | 30.1 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 6 | 30.1 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 9 | 27.8 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 12 | 29.0 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 16 | 25.2 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 19 | 23.1 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 22 | 25.2 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 25 | 24.5 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 25 | 13.7 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 3 | 21.4 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 16 | 12.4 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 6 | 19.8 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 22 | 16.3 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 9 | 23.1 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 19 | 13.7 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 | Month 12 | 17.6 Percentage of participants |
Secondary
Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover
Percentage of participants with a reduction of mean GH levels to \< 2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Denominator for all time points is the Crossover Analysis Set (CAS).
Time frame: Months 3, 6, 9, 12 after crossover
Population: Crossover Analysis Set (CAS): All patients whose first dose in the extension is different from the first dose in the core.~Patients were analyzed according to the crossover treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover | M3 after crossover | 17.3 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover | M6 after crossover | 21.0 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover | M9 after crossover | 22.2 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover | M12 after crossover | 17.3 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover | M12 after crossover | 0.0 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover | M3 after crossover | 2.6 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover | M9 after crossover | 5.3 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With a Reduction of Mean GH Level to < 2.5μg/L and Normalization of IGF-1 After Crossover | M6 after crossover | 2.6 Percentage of participants |
Secondary
Percentage of Participants With Normalization of IGF-1
Percentage of participants with normalization of sex- and age-adjusted IGF-1. Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
Time frame: 12 Months
Population: Full Analysis Set: All patients (Pts) who were randomized into the study. Pts were analyzed according to the treatment they were assigned to at randomization. Missing IGF-1 levels at Month 12 were imputed using data obtained at or after Month 6 by the LOCF (last observation carried forward) method; otherwise, Pts were considered as nonresponders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | De novo | 30.5 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | Overall | 38.6 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | Post surgery | 50.7 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | Overall | 23.6 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | Post surgery | 26.9 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | De novo | 21.2 Percentage of participants |
Secondary
Percentage of Participants With Normalization of IGF-1
Percentage of participants with normalization of sex- and age-adjusted IGF-1. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included). Denominator for time points up to Month 12 is the FAS. Denominator for time points after Month 12 excludes patients who completed the core and did not enter the extension. Patients who discontinued were considered non-responders for the time points after discontinuation, patients who crossed over were considered non-responders for all time points after crossover.
Time frame: Months 3, 6, 9, 12, 16, 19, 22, 25
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M3 | 35.2 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M6 | 35.8 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M9 | 34.1 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M12 | 35.8 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M16 | 29.9 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M19 | 25.2 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M22 | 25.9 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M25 | 25.9 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M25 | 14.4 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M3 | 25.3 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M16 | 13.7 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M6 | 24.2 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M22 | 17.0 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M9 | 28.0 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M19 | 15.7 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 | M12 | 22.0 Percentage of participants |
Secondary
Percentage of Participants With Normalization of IGF-1 After Crossover
Percentage of participants with normalization of sex- and age-adjusted IGF-1. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Denominator for all time points is the Crossover Analysis Set (CAS).
Time frame: Months 3, 6, 9, 12 after crossover
Population: CAS: All patients whose first dose in the extension is different from the first dose in the core. Patients were analyzed according to the crossover treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 After Crossover | M3 after crossover | 19.8 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 After Crossover | M6 after crossover | 30.9 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 After Crossover | M9 after crossover | 29.6 Percentage of participants |
| Pasireotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 After Crossover | M12 after crossover | 27.2 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 After Crossover | M12 after crossover | 5.3 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 After Crossover | M3 after crossover | 7.9 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 After Crossover | M9 after crossover | 10.5 Percentage of participants |
| Octreotide LAR (Core) | Percentage of Participants With Normalization of IGF-1 After Crossover | M6 after crossover | 7.9 Percentage of participants |
Secondary
Ring Size
Ring size (based on jeweler's finger gauge). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Time frame: Baseline, Months 12, 25
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Ring Size | Baseline left hand (LH) 4th digit | 11.6 ring zize | Standard Deviation 2 |
| Pasireotide LAR (Core) | Ring Size | Baseline left hand 5th digit | 11.7 ring zize | Standard Deviation 2.82 |
| Pasireotide LAR (Core) | Ring Size | Baseline right hand (RH) 4th digit | 12.5 ring zize | Standard Deviation 2.01 |
| Pasireotide LAR (Core) | Ring Size | Baseline right hand 5th digit | 11.2 ring zize | Standard Deviation 3.35 |
| Pasireotide LAR (Core) | Ring Size | M12 LH 4th digit | 10.6 ring zize | Standard Deviation 2.05 |
| Pasireotide LAR (Core) | Ring Size | M12 LH 5th digit | 11.8 ring zize | Standard Deviation 1.81 |
| Pasireotide LAR (Core) | Ring Size | M12 RH 4th digit | 12.2 ring zize | Standard Deviation 2.12 |
| Pasireotide LAR (Core) | Ring Size | M12 RH 5th digit | 10.7 ring zize | Standard Deviation 3.96 |
| Pasireotide LAR (Core) | Ring Size | M25 LH 4th digit | 10.1 ring zize | Standard Deviation 2.12 |
| Pasireotide LAR (Core) | Ring Size | M25 LH 5th digit | 10.0 ring zize | Standard Deviation 2.45 |
| Pasireotide LAR (Core) | Ring Size | M25 RH 4th digit | 11.8 ring zize | Standard Deviation 1.98 |
| Pasireotide LAR (Core) | Ring Size | M25 RH 5th digit | 7.8 ring zize | Standard Deviation 4.6 |
| Octreotide LAR (Core) | Ring Size | M25 RH 4th digit | 10.9 ring zize | Standard Deviation 1.65 |
| Octreotide LAR (Core) | Ring Size | Baseline left hand (LH) 4th digit | 11.8 ring zize | Standard Deviation 1.97 |
| Octreotide LAR (Core) | Ring Size | M12 RH 4th digit | 11.3 ring zize | Standard Deviation 2.18 |
| Octreotide LAR (Core) | Ring Size | Baseline left hand 5th digit | 12.4 ring zize | Standard Deviation 2.88 |
| Octreotide LAR (Core) | Ring Size | M25 LH 5th digit | 14.3 ring zize | Standard Deviation 0.35 |
| Octreotide LAR (Core) | Ring Size | Baseline right hand (RH) 4th digit | 11.4 ring zize | Standard Deviation 2.54 |
| Octreotide LAR (Core) | Ring Size | M12 RH 5th digit | 10.5 ring zize | Standard Deviation 2.14 |
| Octreotide LAR (Core) | Ring Size | Baseline right hand 5th digit | 11.3 ring zize | Standard Deviation 2.95 |
| Octreotide LAR (Core) | Ring Size | M25 RH 5th digit | 7.5 ring zize | — |
| Octreotide LAR (Core) | Ring Size | M12 LH 4th digit | 11.1 ring zize | Standard Deviation 1.95 |
| Octreotide LAR (Core) | Ring Size | M25 LH 4th digit | 11.1 ring zize | Standard Deviation 1.95 |
| Octreotide LAR (Core) | Ring Size | M12 LH 5th digit | 12.4 ring zize | Standard Deviation 1.78 |
Secondary
Ring Size After Crossover
Ring size (based on jeweler's finger gauge). Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). BL = baseline, LH = left hand, RH = right hand, CO = crossover
Time frame: Extension baseline, month 12 after crossover
Population: CAS: All patients whose first dose in the extension is different from the first dose in the core. Patients were analyzed according to the crossover treatment received. In the extension baseline, no participant had ring size on their right hand measured at the 5th digit, hence no data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Ring Size After Crossover | M12 after CO RH 5th digit | 11.5 ring size | Standard Deviation 0 |
| Pasireotide LAR (Core) | Ring Size After Crossover | Ext. BL RH 4th digit | 11.4 ring size | Standard Deviation 2.42 |
| Pasireotide LAR (Core) | Ring Size After Crossover | Ext. BL RH 5th digit | 10.7 ring size | Standard Deviation 2.31 |
| Pasireotide LAR (Core) | Ring Size After Crossover | M12 after CO LH 4th digit | 10.9 ring size | Standard Deviation 2.27 |
| Pasireotide LAR (Core) | Ring Size After Crossover | M12 after CO LH 5th digit CO | 11.9 ring size | Standard Deviation 2.14 |
| Pasireotide LAR (Core) | Ring Size After Crossover | M12 after CO RH 4th digit | 11.6 ring size | Standard Deviation 2.95 |
| Pasireotide LAR (Core) | Ring Size After Crossover | Ext. BL LH 4th digit | 11.2 ring size | Standard Deviation 2.1 |
| Pasireotide LAR (Core) | Ring Size After Crossover | Ext. BL LH 5th digit | 11.6 ring size | Standard Deviation 1.88 |
| Octreotide LAR (Core) | Ring Size After Crossover | M12 after CO LH 4th digit | 11.2 ring size | Standard Deviation 2.01 |
| Octreotide LAR (Core) | Ring Size After Crossover | Ext. BL LH 4th digit | 11.0 ring size | Standard Deviation 1.87 |
| Octreotide LAR (Core) | Ring Size After Crossover | M12 after CO RH 4th digit | 11.4 ring size | Standard Deviation 2.56 |
| Octreotide LAR (Core) | Ring Size After Crossover | Ext. BL LH 5th digit | 12.3 ring size | Standard Deviation 2.46 |
| Octreotide LAR (Core) | Ring Size After Crossover | M12 after CO LH 5th digit CO | 12.5 ring size | Standard Deviation 1.35 |
| Octreotide LAR (Core) | Ring Size After Crossover | Ext. BL RH 4th digit | 12.4 ring size | Standard Deviation 2.11 |
Secondary
Severity Scores of Acromegaly Symptoms
Severity scores of acromegaly symptoms (Headache, Fatigue, Perspiration, Paresthesias, Osteoarthralgia). Symptoms were scored from 0 (no symptom) to 4 (very severe). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Time frame: Baseline, Months 12, 25
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Perspiration - M25 | 0.4 scores on a scale | Standard Deviation 0.72 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Paresthesia - M25 | 0.2 scores on a scale | Standard Deviation 0.49 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Headache - Baseline | 0.9 scores on a scale | Standard Deviation 1.05 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Fatigue - Baseline | 1.2 scores on a scale | Standard Deviation 1.13 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Perspiration - Baseline | 1.1 scores on a scale | Standard Deviation 1.21 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Paresthesia - Baseline | 0.7 scores on a scale | Standard Deviation 1 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Osteoarthraliga - Baseline | 1.0 scores on a scale | Standard Deviation 1.05 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Headache - M12 | 0.5 scores on a scale | Standard Deviation 0.77 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Fatigue - M12 | 0.8 scores on a scale | Standard Deviation 0.95 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Perspiration - M12 | 0.4 scores on a scale | Standard Deviation 0.81 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Paresthesia - M12 | 0.3 scores on a scale | Standard Deviation 0.63 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Osteoarthraliga - M12 | 0.5 scores on a scale | Standard Deviation 0.8 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Headache - M25 | 0.4 scores on a scale | Standard Deviation 0.61 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Fatigue - M25 | 0.5 scores on a scale | Standard Deviation 0.71 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Osteoarthraliga - M25 | 0.4 scores on a scale | Standard Deviation 0.79 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Osteoarthraliga - M25 | 0.8 scores on a scale | Standard Deviation 1.07 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Perspiration - M25 | 0.4 scores on a scale | Standard Deviation 0.67 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Headache - M12 | 0.6 scores on a scale | Standard Deviation 0.79 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Paresthesia - M12 | 0.4 scores on a scale | Standard Deviation 0.72 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Osteoarthraliga - M12 | 0.7 scores on a scale | Standard Deviation 1 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Headache - Baseline | 1.0 scores on a scale | Standard Deviation 1.14 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Fatigue - M12 | 0.7 scores on a scale | Standard Deviation 0.99 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Fatigue - Baseline | 1.4 scores on a scale | Standard Deviation 1.23 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Paresthesia - M25 | 0.4 scores on a scale | Standard Deviation 0.67 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Perspiration - Baseline | 1.3 scores on a scale | Standard Deviation 1.31 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Perspiration - M12 | 0.5 scores on a scale | Standard Deviation 0.91 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Paresthesia - Baseline | 0.8 scores on a scale | Standard Deviation 1.15 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Headache - M25 | 0.6 scores on a scale | Standard Deviation 0.77 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Osteoarthraliga - Baseline | 1.3 scores on a scale | Standard Deviation 1.26 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms | Fatigue - M25 | 0.7 scores on a scale | Standard Deviation 0.89 |
Secondary
Severity Scores of Acromegaly Symptoms After Crossover
Severity scores of acromegaly symptoms (Headache, Fatigue, Perspiration, Paresthesias, Osteoarthralgia). Symptoms were scored from 0 (no symptom) to 4 (very severe). Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over).
Time frame: Extension baseline, month 12 after crossover
Population: CAS: All patients whose first dose in the extension is different from the first dose in the core. Patients were analyzed according to the crossover treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Fatigue: Ext. BL | 0.8 scores on a scale | Standard Deviation 1.07 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Perspiration: M12 after crossover | 0.6 scores on a scale | Standard Deviation 0.98 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Headache: M12 after crossover | 0.5 scores on a scale | Standard Deviation 0.83 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Paresthesia: Ext. BL | 0.4 scores on a scale | Standard Deviation 0.75 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Fatigue: M12 after crossover | 0.8 scores on a scale | Standard Deviation 0.91 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Paresthesia: M12 after crossover | 0.3 scores on a scale | Standard Deviation 0.56 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Headache: Ext. BL | 0.6 scores on a scale | Standard Deviation 0.89 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Osteoarthralgia: Ext. BL | 0.6 scores on a scale | Standard Deviation 0.91 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Perspiration: Ext. BL | 0.5 scores on a scale | Standard Deviation 0.85 |
| Pasireotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Osteoarthralgia: M12 after crossover | 0.5 scores on a scale | Standard Deviation 0.89 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Osteoarthralgia: M12 after crossover | 0.7 scores on a scale | Standard Deviation 0.86 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Headache: Ext. BL | 0.4 scores on a scale | Standard Deviation 0.6 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Headache: M12 after crossover | 0.7 scores on a scale | Standard Deviation 0.79 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Fatigue: Ext. BL | 0.7 scores on a scale | Standard Deviation 0.76 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Fatigue: M12 after crossover | 0.7 scores on a scale | Standard Deviation 0.68 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Perspiration: Ext. BL | 0.6 scores on a scale | Standard Deviation 0.86 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Perspiration: M12 after crossover | 0.5 scores on a scale | Standard Deviation 0.8 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Paresthesia: Ext. BL | 0.4 scores on a scale | Standard Deviation 0.054 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Paresthesia: M12 after crossover | 0.4 scores on a scale | Standard Deviation 0.76 |
| Octreotide LAR (Core) | Severity Scores of Acromegaly Symptoms After Crossover | Osteoarthralgia: Ext. BL | 0.6 scores on a scale | Standard Deviation 0.79 |
Secondary
Summary of Mean GH Values
Mean GH levels (based on a 5-point profile over 2 hours). Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Time frame: Baseline, Months 3, 6, 9, 12, 16, 19, 22, 25
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Summary of Mean GH Values | Month 3 | 6.3 μg/L | Standard Deviation 12.54 |
| Pasireotide LAR (Core) | Summary of Mean GH Values | Month 16 | 2.3 μg/L | Standard Deviation 5.64 |
| Pasireotide LAR (Core) | Summary of Mean GH Values | Month 9 | 4.9 μg/L | Standard Deviation 9.62 |
| Pasireotide LAR (Core) | Summary of Mean GH Values | Month 19 | 2.1 μg/L | Standard Deviation 5.68 |
| Pasireotide LAR (Core) | Summary of Mean GH Values | Month 6 | 5.6 μg/L | Standard Deviation 11.47 |
| Pasireotide LAR (Core) | Summary of Mean GH Values | Month 22 | 2.1 μg/L | Standard Deviation 6.15 |
| Pasireotide LAR (Core) | Summary of Mean GH Values | Month 12 | 4.6 μg/L | Standard Deviation 9.51 |
| Pasireotide LAR (Core) | Summary of Mean GH Values | Month 25 | 2.0 μg/L | Standard Deviation 5.02 |
| Pasireotide LAR (Core) | Summary of Mean GH Values | Baseline | 21.9 μg/L | Standard Deviation 32.14 |
| Octreotide LAR (Core) | Summary of Mean GH Values | Month 25 | 1.2 μg/L | Standard Deviation 1.11 |
| Octreotide LAR (Core) | Summary of Mean GH Values | Baseline | 18.8 μg/L | Standard Deviation 25.95 |
| Octreotide LAR (Core) | Summary of Mean GH Values | Month 3 | 5.8 μg/L | Standard Deviation 12.87 |
| Octreotide LAR (Core) | Summary of Mean GH Values | Month 6 | 5.2 μg/L | Standard Deviation 10.99 |
| Octreotide LAR (Core) | Summary of Mean GH Values | Month 9 | 4.3 μg/L | Standard Deviation 9.7 |
| Octreotide LAR (Core) | Summary of Mean GH Values | Month 12 | 4.5 μg/L | Standard Deviation 11.34 |
| Octreotide LAR (Core) | Summary of Mean GH Values | Month 16 | 1.4 μg/L | Standard Deviation 1.49 |
| Octreotide LAR (Core) | Summary of Mean GH Values | Month 19 | 1.5 μg/L | Standard Deviation 1.68 |
| Octreotide LAR (Core) | Summary of Mean GH Values | Month 22 | 1.4 μg/L | Standard Deviation 1.43 |
Secondary
Summary of Mean GH Values After Crossover
Mean GH levels (based on a 5-point profile over 2 hours). Extension baseline was defined as last measurement prior to the start of crossover treatment. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over).
Time frame: Extension baseline, months 3, 6, 9, 12 after crossover
Population: CAS: All patients whose first dose in the extension is different from the first dose in the core. Patients were analyzed according to the crossover treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Summary of Mean GH Values After Crossover | Ext. Baseline | 5.9 μg/L | Standard Deviation 15.02 |
| Pasireotide LAR (Core) | Summary of Mean GH Values After Crossover | M6 after crossover | 4.8 μg/L | Standard Deviation 14.51 |
| Pasireotide LAR (Core) | Summary of Mean GH Values After Crossover | M9 after crossover | 2.6 μg/L | Standard Deviation 3.03 |
| Pasireotide LAR (Core) | Summary of Mean GH Values After Crossover | M12 after crossover | 2.5 μg/L | Standard Deviation 2.47 |
| Pasireotide LAR (Core) | Summary of Mean GH Values After Crossover | M3 after crossover | 5.9 μg/L | Standard Deviation 19.7 |
| Octreotide LAR (Core) | Summary of Mean GH Values After Crossover | M12 after crossover | 10.4 μg/L | Standard Deviation 26 |
| Octreotide LAR (Core) | Summary of Mean GH Values After Crossover | Ext. Baseline | 7.1 μg/L | Standard Deviation 9.8 |
| Octreotide LAR (Core) | Summary of Mean GH Values After Crossover | M3 after crossover | 9.8 μg/L | Standard Deviation 17.09 |
| Octreotide LAR (Core) | Summary of Mean GH Values After Crossover | M9 after crossover | 8.7 μg/L | Standard Deviation 19.26 |
| Octreotide LAR (Core) | Summary of Mean GH Values After Crossover | M6 after crossover | 9.8 μg/L | Standard Deviation 20.49 |
Secondary
Summary of Prolactin Levels
Prolactin Levels. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Time frame: Baseline, Months 12, 25
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Summary of Prolactin Levels | Baseline | 20.6 μg/L | Standard Deviation 53 |
| Pasireotide LAR (Core) | Summary of Prolactin Levels | M12 | 8.9 μg/L | Standard Deviation 19.24 |
| Pasireotide LAR (Core) | Summary of Prolactin Levels | M25 | 5.4 μg/L | Standard Deviation 4.37 |
| Octreotide LAR (Core) | Summary of Prolactin Levels | Baseline | 15.8 μg/L | Standard Deviation 22.05 |
| Octreotide LAR (Core) | Summary of Prolactin Levels | M12 | 11.7 μg/L | Standard Deviation 19.09 |
| Octreotide LAR (Core) | Summary of Prolactin Levels | M25 | 6.7 μg/L | Standard Deviation 4.63 |
Secondary
Summary of Prolactin Levels After Crossover
Prolactin (PRL) levels. Analysis was based on data after crossover (i.e., included data from blinded extension phase collected after the crossover time point for patients who crossed over). Extension baseline was defined as last measurement prior to the start of crossover treatment.
Time frame: Extension baseline, month 12 after crossover
Population: CAS: All patients whose first dose in the extension is different from the first dose in the core. Patients were analyzed according to the crossover treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide LAR (Core) | Summary of Prolactin Levels After Crossover | Ext. Baseline | 11.9 μg/L | Standard Deviation 18.42 |
| Pasireotide LAR (Core) | Summary of Prolactin Levels After Crossover | M12 after crossover | 7.5 μg/L | Standard Deviation 8.95 |
| Octreotide LAR (Core) | Summary of Prolactin Levels After Crossover | Ext. Baseline | 15.7 μg/L | Standard Deviation 36.76 |
| Octreotide LAR (Core) | Summary of Prolactin Levels After Crossover | M12 after crossover | 16.1 μg/L | Standard Deviation 25.37 |
Secondary
Time to First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 (No. of Responders: Pasireotite LAR = 81, Octreotide LAR = 63) )
Time to first response for patients achieving a reduction of mean GH level to \< 2.5 μg/L and normalization of IGF-1. Analysis was based on data up to crossover (i.e., included data from both blinded core and extension phase up to 26 Months for patients who continued the same treatment in the extension. For patients who switched to the other treatment, only data collected before crossover was included).
Time frame: Up to 26 months
Population: Full Analysis Set: All patients who were randomized into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pasireotide LAR (Core) | Time to First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 (No. of Responders: Pasireotite LAR = 81, Octreotide LAR = 63) ) | 12.6 Weeks |
| Octreotide LAR (Core) | Time to First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 (No. of Responders: Pasireotite LAR = 81, Octreotide LAR = 63) ) | 12.4 Weeks |