Trial Outcomes & Findings for Evaluate the Efficacy and Safety of Pasireotide LAR (Long Acting Release) on the Treatment of Patients With Clinically Non-Functioning Pituitary Adenoma. (NCT NCT01283542)

NCT ID: NCT01283542

Last Updated: 2019-04-26

Results Overview

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility.The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. A change ≥ 20% in the original volume of the tumor was considered to be clinically significant. Evaluable participants required tumor volume assessment at baseline and at week 24.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: Baseline up to 24 weeks
• Results posted on: 2019-04-26

Participant Flow

Twenty seven patients were screened and 21 met eligibility requirements.

Participant milestones

Measure	Pasireotide LAR All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks
Main Phase STARTED	20
Main Phase Full Analysis Set (FAS)	20
Main Phase Safety Analysis Set	20
Main Phase COMPLETED	13
Main Phase NOT COMPLETED	7
Extension Phase STARTED	13
Extension Phase Full Analysis Set (FAS)	13
Extension Phase Safety Analysis Set	13
Extension Phase COMPLETED	10
Extension Phase NOT COMPLETED	3

Reasons for withdrawal

Measure	Pasireotide LAR All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks
Main Phase Acute or progressive vision loss	1
Main Phase Uncontrolled diabetes mellitus	1
Main Phase abnormal laboratory values	5
Extension Phase Physician Decision	1
Extension Phase Adverse Event	1
Extension Phase Administrative problems	1

Baseline Characteristics

Evaluate the Efficacy and Safety of Pasireotide LAR (Long Acting Release) on the Treatment of Patients With Clinically Non-Functioning Pituitary Adenoma.

Baseline characteristics by cohort

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks
Age, Continuous	55.65 years STANDARD_DEVIATION 11.72 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian ancestry	13 Participants n=5 Participants
Race/Ethnicity, Customized Black/African ancestry	5 Participants n=5 Participants
Race/Ethnicity, Customized Asian ancestry	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Body mass index (BMI)	26.95 kg/m2 STANDARD_DEVIATION 4.53 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 24 weeks

Population: Evaluable participants required tumor volume assessment at baseline and at week 24

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility.The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. A change ≥ 20% in the original volume of the tumor was considered to be clinically significant. Evaluable participants required tumor volume assessment at baseline and at week 24.

Outcome measures

Measure	Pasireotide LAR n=12 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Percentage of Participants With Non-functioning Pituitary Adenomas (NFPA) Who Achieve Tumor Volume Reduction of at Least 20% After 24 Weeks (FAS)	16.7 percentage of participants Interval 2.1 to 48.4	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 4, 12, 24

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Tumor Volume Main Phase (FAS) Main Baseline	2.97 cm^3 Standard Deviation 2.53	—	—	—	—	—	—
Tumor Volume Main Phase (FAS) Main Week 4	4.31 cm^3 Standard Deviation 6.66	—	—	—	—	—	—
Tumor Volume Main Phase (FAS) Main Week 12	4.31 cm^3 Standard Deviation 6.66	—	—	—	—	—	—
Tumor Volume Main Phase (FAS) Main Week 24	3.39 cm^3 Standard Deviation 3.15	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 48, 72, 96

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=13 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Tumor Volume in Extension Phase (FAS) Extension Week 48	3.57 cm^3 Standard Deviation 3.25	—	—	—	—	—	—
Tumor Volume in Extension Phase (FAS) Extension Week 72	3.12 cm^3 Standard Deviation 2.48	—	—	—	—	—	—
Tumor Volume in Extension Phase (FAS) Extension Week 96	1.70 cm^3 Standard Deviation 1.02	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 4, 12, 24

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Tumor Volume Change From Baseline in Main Phase (FAS) Main Week 4	1.25 cm^3 Interval -1.7 to 4.2	—	—	—	—	—	—
Tumor Volume Change From Baseline in Main Phase (FAS) Main Week 12	0.66 cm^3 Interval -0.45 to 1.76	—	—	—	—	—	—
Tumor Volume Change From Baseline in Main Phase (FAS) Main Week 24	0.23 cm^3 Interval -1.24 to 1.71	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 48, 72, 96

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=13 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Tumor Volume Change From Baseline in Extension Phase (FAS) Extension Week 48	0.53 cm^3 Standard Deviation 2.19	—	—	—	—	—	—
Tumor Volume Change From Baseline in Extension Phase (FAS) Extension Week 72	-0.14 cm^3 Standard Deviation 0.63	—	—	—	—	—	—
Tumor Volume Change From Baseline in Extension Phase (FAS) Extension Week 96	0.0 cm^3 Standard Deviation 0.90	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 4, 12, 24

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Tumor Volume Percent Change From Baseline in Main Phase (FAS) Main Week 4	36.92 percent change Interval -52.11 to 125.94	—	—	—	—	—	—
Tumor Volume Percent Change From Baseline in Main Phase (FAS) Main Week 12	39.36 percent change Interval -42.19 to 120.91	—	—	—	—	—	—
Tumor Volume Percent Change From Baseline in Main Phase (FAS) Main Week 24	7.98 percent change Interval -32.79 to 48.74	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 48, 72, 96

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=13 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Tumor Volume Percent Change From Baseline in Extension Phase (FAS) Extension Week 48	14.83 percent change Standard Deviation 67.28	—	—	—	—	—	—
Tumor Volume Percent Change From Baseline in Extension Phase (FAS) Extension Week 72	-2.57 percent change Standard Deviation 14.33	—	—	—	—	—	—
Tumor Volume Percent Change From Baseline in Extension Phase (FAS) Extension Week 96	-1.59 percent change Standard Deviation 53.09	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 4, 12, 24

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Percentage of Patients Achieving Tumour Volume Reduction in Main Phase (FAS) Week 4	47.4 percentage of patients	—	—	—	—	—	—
Percentage of Patients Achieving Tumour Volume Reduction in Main Phase (FAS) Week 12	41.2 percentage of patients	—	—	—	—	—	—
Percentage of Patients Achieving Tumour Volume Reduction in Main Phase (FAS) Week 24	75.0 percentage of patients	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 4, 12, 24

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Main Phase (FAS) Main Week 4	10.5 percentage of patients Interval 1.3 to 33.1	—	—	—	—	—	—
Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Main Phase (FAS) Main Week 12	5.9 percentage of patients Interval 0.1 to 28.7	—	—	—	—	—	—
Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Main Phase (FAS) Main Week 24	16.7 percentage of patients Interval 2.1 to 48.4	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 48, 72, 96

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=13 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Percentage of Patients Achieving Tumour Volume Reduction in Extension Phase (FAS) Extension Week 48	10.0 percentage of patients	—	—	—	—	—	—
Percentage of Patients Achieving Tumour Volume Reduction in Extension Phase (FAS) Extension Week 72	12.5 percentage of patients	—	—	—	—	—	—
Percentage of Patients Achieving Tumour Volume Reduction in Extension Phase (FAS) Extension Week 96	50.0 percentage of patients	—	—	—	—	—	—

SECONDARY outcome

Timeframe: baseline to week 48, 72, 96

Population: number of participants with evaluable data varied across visits

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

Outcome measures

Measure	Pasireotide LAR n=13 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 Week 4 of Main Phase	Week 12 Week 12 of Main Phase	Week 24 Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Extension Phase (FAS) Extension Week 48	10.0 percentage of patients	—	—	—	—	—	—
Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Extension Phase (FAS) Extension Week 72	12.5 percentage of patients	—	—	—	—	—	—
Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Extension Phase (FAS) Extension Week 96	50.0 percentage of patients	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and at weeks 4, 12,24,48,72, 96

Population: number of participants varied across visits

The absence and presence of disease-related symptoms were reported by patients and recorded by the medical staff. Patients classified the symptoms according to a 5-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 n=20 Participants Week 4 of Main Phase	Week 12 n=19 Participants Week 12 of Main Phase	Week 24 n=20 Participants Week 24 of Main Phase	Week 48 n=13 Participants Week 48 of Extension Phase	Week 72 n=12 Participants Week 72 of Extension Phase	Week 96 n=11 Participants Week 96 of Extension Phase
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Headache Absent	45.0 percentage of participants	75.0 percentage of participants	52.6 percentage of participants	45.0 percentage of participants	61.5 percentage of participants	58.3 percentage of participants	70.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Headache Mild	30.0 percentage of participants	10.0 percentage of participants	36.8 percentage of participants	45.0 percentage of participants	7.7 percentage of participants	8.3 percentage of participants	0.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Headache Moderate	25.0 percentage of participants	15.0 percentage of participants	10.5 percentage of participants	10.0 percentage of participants	30.8 percentage of participants	33.3 percentage of participants	20.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Headache Severe	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	10.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Visual Disturbances Absent	80.0 percentage of participants	80.0 percentage of participants	84.2 percentage of participants	85.0 percentage of participants	76.9 percentage of participants	83.3 percentage of participants	80.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Visual Disturbances Mild	10.0 percentage of participants	10.0 percentage of participants	10.5 percentage of participants	10.0 percentage of participants	7.7 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Visual Disturbances Moderate	5.0 percentage of participants	5.0 percentage of participants	5.3 percentage of participants	5.0 percentage of participants	15.4 percentage of participants	16.7 percentage of participants	20.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Visual Disturbances Severe	5.0 percentage of participants	5.0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Fatigue Absent	80.0 percentage of participants	80.0 percentage of participants	73.7 percentage of participants	75.0 percentage of participants	69.2 percentage of participants	58.3 percentage of participants	70.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Fatigue Mild	15.0 percentage of participants	15.0 percentage of participants	21.1 percentage of participants	20.0 percentage of participants	30.8 percentage of participants	33.3 percentage of participants	30.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Fatigue Moderate	5.0 percentage of participants	0 percentage of participants	5.3 percentage of participants	5.0 percentage of participants	0 percentage of participants	8.3 percentage of participants	0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Fatigue Severe	0 percentage of participants	5.0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Decreased libido Absent	55.0 percentage of participants	65.0 percentage of participants	68.4 percentage of participants	65.0 percentage of participants	61.5 percentage of participants	66.7 percentage of participants	70.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Decreased libido Mild	10.0 percentage of participants	10.0 percentage of participants	10.5 percentage of participants	10.0 percentage of participants	23.1 percentage of participants	25.0 percentage of participants	0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Decreased libido Moderate	20.0 percentage of participants	10.0 percentage of participants	5.3 percentage of participants	10.0 percentage of participants	0 percentage of participants	0 percentage of participants	20.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Decreased libido Severe	5.0 percentage of participants	15.0 percentage of participants	15.8 percentage of participants	15.0 percentage of participants	15.4 percentage of participants	8.3 percentage of participants	10.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Decreased libido Very severe	10.0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Erectile dysfunction Yes	22.2 percentage of participants	11.1 percentage of participants	11.1 percentage of participants	11.1 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Erectile dysfunction No	77.8 percentage of participants	88.9 percentage of participants	88.9 percentage of participants	88.9 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Regular Menses Yes	45.5 percentage of participants	55.6 percentage of participants	62.5 percentage of participants	55.6 percentage of participants	60.0 percentage of participants	50.0 percentage of participants	50.0 percentage of participants
Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) Regular Menses No	54.5 percentage of participants	44.4 percentage of participants	37.5 percentage of participants	44.4 percentage of participants	40.0 percentage of participants	50.0 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and at weeks 24, 48, 96

Population: number of participants with evaluable data varied across visits

Hormone levels, including those of GH, IGF-1, and prolactin were evaluated by a central lab

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 n=20 Participants Week 4 of Main Phase	Week 12 n=13 Participants Week 12 of Main Phase	Week 24 n=11 Participants Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Mean GH and IGF-1 Hormone Levels During Main and Extension Phases (FAS) GH	0.31 ng/mL Standard Deviation 0.63	1.11 ng/mL Standard Deviation 4.10	0.15 ng/mL Standard Deviation 0.15	0.12 ng/mL Standard Deviation 0.07	—	—	—
Mean GH and IGF-1 Hormone Levels During Main and Extension Phases (FAS) IGF-1	130.73 ng/mL Standard Deviation 44.4	72.59 ng/mL Standard Deviation 35.55	66.23 ng/mL Standard Deviation 31.46	70.82 ng/mL Standard Deviation 32.67	—	—	—
Mean GH and IGF-1 Hormone Levels During Main and Extension Phases (FAS) Prolactin	16.90 ng/mL Standard Deviation 12.91	13.89 ng/mL Standard Deviation 17.32	9.03 ng/mL Standard Deviation 6.27	7.62 ng/mL Standard Deviation 8.33	—	—	—

SECONDARY outcome

Timeframe: Baseline and at weeks 24, 48, 96

Population: participants with evaluable data varied across visits

Hormone levels, including those of growth hormone (GH),insulin-like growth factor 1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free thyroxine (free T4), and estradiol (for women) or testosterone (for men), were evaluated by a central lab

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 n=20 Participants Week 4 of Main Phase	Week 12 n=13 Participants Week 12 of Main Phase	Week 24 n=11 Participants Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Mean ACTH and Estradiol Hormone Levels During Main and Extension Phases (FAS) ACTH	28.91 pg/mL Standard Deviation 37.07	23.18 pg/mL Standard Deviation 31.67	36.06 pg/mL Standard Deviation 33.09	29.90 pg/mL Standard Deviation 26.83	—	—	—
Mean ACTH and Estradiol Hormone Levels During Main and Extension Phases (FAS) Estradiol	35.72 pg/mL Standard Deviation 21.03	32.12 pg/mL Standard Deviation 17.71	34.69 pg/mL Standard Deviation 14.74	19.98 pg/mL Standard Deviation 15.78	—	—	—

SECONDARY outcome

Timeframe: Baseline and at weeks 24, 48, 96

Population: number participants with evaluable data varied across visits

Hormone levels, including those of GH, IGF-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free T4, and estradiol (for women) or testosterone (for men), were evaluated by a central lab

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 n=20 Participants Week 4 of Main Phase	Week 12 n=13 Participants Week 12 of Main Phase	Week 24 n=11 Participants Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Mean Cortisol Hormone Levels During Main and Extension Phases (FAS)	12.60 µg/dL Standard Deviation 4.37	16.41 µg/dL Standard Deviation 8.28	12.12 µg/dL Standard Deviation 4.43	10.09 µg/dL Standard Deviation 3.12	—	—	—

SECONDARY outcome

Timeframe: Baseline and at weeks 24, 48, 96

Population: participants with evaluable data varied across visits

Hormone levels, including those of GH, IGF-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free T4, and estradiol (for women) or testosterone (for men), were evaluated by a central lab

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 n=20 Participants Week 4 of Main Phase	Week 12 n=13 Participants Week 12 of Main Phase	Week 24 n=11 Participants Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Mean LH and FSH Hormone Levels During Main and Extension Phases (FAS) LH	5.57 mUI/mL Standard Deviation 6.91	5.32 mUI/mL Standard Deviation 7.25	7.44 mUI/mL Standard Deviation 7.07	9.95 mUI/mL Standard Deviation 9.56	—	—	—
Mean LH and FSH Hormone Levels During Main and Extension Phases (FAS) FSH	11.83 mUI/mL Standard Deviation 18.89	12.90 mUI/mL Standard Deviation 20.00	16.23 mUI/mL Standard Deviation 20.97	21.45 mUI/mL Standard Deviation 24.56	—	—	—

SECONDARY outcome

Timeframe: Baseline and at weeks 24, 48, 96

Population: participants with evaluable data varied across visits

Hormone levels, including those of GH, IGF-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free T4, and estradiol (for women) or testosterone (for men), were evaluated by a central lab

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 n=20 Participants Week 4 of Main Phase	Week 12 n=13 Participants Week 12 of Main Phase	Week 24 n=11 Participants Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Mean Testosterone and Free T4 Hormone Levels During Main and Extension Phases (FAS) Testosterone	452.21 ng/dL Standard Deviation 214.52	372.72 ng/dL Standard Deviation 205.25	517.52 ng/dL Standard Deviation 200.64	382.10 ng/dL Standard Deviation 179.79	—	—	—
Mean Testosterone and Free T4 Hormone Levels During Main and Extension Phases (FAS) Free T4	1.07 ng/dL Standard Deviation 0.12	1.13 ng/dL Standard Deviation 0.18	1.17 ng/dL Standard Deviation 0.17	1.04 ng/dL Standard Deviation 0.25	—	—	—

SECONDARY outcome

Timeframe: Baseline and at weeks 24, 48, 96

Population: participants with evaluable data varied across visits

Hormone levels, including those of GH, IGF-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free T4, and estradiol (for women) or testosterone (for men), were evaluated by a central lab

Outcome measures

Measure	Pasireotide LAR n=20 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 n=20 Participants Week 4 of Main Phase	Week 12 n=13 Participants Week 12 of Main Phase	Week 24 n=11 Participants Week 24 of Main Phase	Week 48 Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Mean TSH Hormone Levels During Main and Extension Phases (FAS)	151.81 µUI/mL Standard Deviation 655.82	149.92 µUI/mL Standard Deviation 628.93	1.67 µUI/mL Standard Deviation 1.27	1.70 µUI/mL Standard Deviation 1.33	—	—	—

SECONDARY outcome

Timeframe: Baseline and at weeks 12,24,48,72, 96

Outcome measures

Measure	Pasireotide LAR n=16 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 n=14 Participants Week 4 of Main Phase	Week 12 n=15 Participants Week 12 of Main Phase	Week 24 n=13 Participants Week 24 of Main Phase	Week 48 n=12 Participants Week 48 of Extension Phase	Week 72 n=11 Participants Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Mean Alpha Subunit Levels in Main and Extension Phases (FAS)	242.27 ng/mL Standard Deviation 286.90	309.04 ng/mL Standard Deviation 270.52	192.11 ng/mL Standard Deviation 201.25	234.21 ng/mL Standard Deviation 182.59	286.78 ng/mL Standard Deviation 288.62	435.00 ng/mL Standard Deviation 310.87	—

SECONDARY outcome

Timeframe: Baseline up to approximately Week 96

Population: Evaluable participants had to have 50% reduction

Alpha subunit levels were determined at a central laboratory.

Outcome measures

Measure	Pasireotide LAR n=14 Participants All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Week 4 n=15 Participants Week 4 of Main Phase	Week 12 n=10 Participants Week 12 of Main Phase	Week 24 n=10 Participants Week 24 of Main Phase	Week 48 n=6 Participants Week 48 of Extension Phase	Week 72 Week 72 of Extension Phase	Week 96 Week 96 of Extension Phase
Percentage of Participants With Reduction From Baseline of Alpha Subunit ≥50% in Main and Extension Phases (FAS)	8.3 percentage of participants	28.6 percentage of participants	12.5 percentage of participants	22.2 percentage of participants	0 percentage of participants	—	—

Adverse Events

Pasireotide LAR

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pasireotide LAR n=20 participants at risk All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks
Hepatobiliary disorders Cholelithiasis	5.0% 1/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Injury, poisoning and procedural complications Hand fracture	5.0% 1/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks

Other adverse events

Measure	Pasireotide LAR n=20 participants at risk All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks
Gastrointestinal disorders Abdominal distension	10.0% 2/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Gastrointestinal disorders Abdominal pain	10.0% 2/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Gastrointestinal disorders Diarrhoea	45.0% 9/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Gastrointestinal disorders Nausea	25.0% 5/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Investigations Blood glucose increased	10.0% 2/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Metabolism and nutrition disorders Diabetes mellitus	25.0% 5/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Metabolism and nutrition disorders Dyslipidaemia	10.0% 2/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Metabolism and nutrition disorders Hyperglycaemia	45.0% 9/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Metabolism and nutrition disorders Type 2 diabetes mellitus	10.0% 2/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 2/20 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 104 weeks

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER