Trial Outcomes & Findings for Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly (NCT NCT01137682)

Last Updated: 2018-04-05

Results Overview

The primary objective of this study was to compare the percentage of patients achieving biochemical control (defined as mean GH levels \<2.5 µg/L and normalization of sex- and age- adjusted IGF-1) at 24 weeks with pasireotide LAR 40 mg and pasireotide LAR 60 mg separately versus continued treatment with octreotide LAR 30 mg or lanreotide autogel (ATG) 120 mg. The primary efficacy variable is the proportion of patients with a reduction of mean GH levels to \< 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

198 participants

Primary outcome timeframe

At 24 weeks

Results posted on

2018-04-05

Participant Flow

One hundred ninety-eight patients were randomized and 5 patients in CORE and 1 patient in extension did not receive any study treatment

Participant milestones

Participant milestones
Measure	Pasireotide LAR 40 mg Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Overall Study STARTED	65	65	68
Overall Study Not Treated	2	2	1
Overall Study Treated	63	63	67
Overall Study Completed 24-Week Core Phase	59	57	65
Overall Study Not Continuing Into Extension	2	3	2
Overall Study Continuing Into Extension	57	54	63
Overall Study Safety Set - CORE	63	62	66
Overall Study Safety Set - Extension	57	54	62
Overall Study COMPLETED	28	25	34
Overall Study NOT COMPLETED	37	40	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Pasireotide LAR 40 mg Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Overall Study Adverse Event-CORE	2	4	0
Overall Study Withdrawal by Subject-CORE	2	2	2
Overall Study Administrative problems-CORE	2	1	0
Overall Study Protocol Violation-CORE	0	1	1
Overall Study Adverse Event-Extension	4	8	7
Overall Study Lack of Efficacy-Extension	15	9	13
Overall Study Withdrawal by Subject-Extension	6	8	8
Overall Study Lost to Follow Up-Extension	0	1	0
Overall Study Administrative problems-Extension	0	2	0
Overall Study Death-Extension	2	0	0
Overall Study Protocol Violation-Extension	2	1	0
Overall Study Did not enter extension	2	3	2
Overall Study Did not receive treatment in extension	0	0	1

Baseline Characteristics

Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pasireotide LAR 40 mg n=65 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)	Pasireotide LAR 60 mg n=65 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)	Control Arm (Octreotide or Lanreotide) n=68 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days	Total n=198 Participants Total of all reporting groups
Age, Customized <65 Years	62 Participants n=5 Participants	57 Participants n=7 Participants	63 Participants n=5 Participants	182 Participants n=4 Participants
Age, Customized ≥ 65 Years	3 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	35 Participants n=7 Participants	38 Participants n=5 Participants	111 Participants n=4 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	30 Participants n=7 Participants	30 Participants n=5 Participants	87 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	53 Participants n=5 Participants	52 Participants n=7 Participants	56 Participants n=5 Participants	161 Participants n=4 Participants
Race/Ethnicity, Customized Black	3 Participants n=5 Participants	8 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Native American	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: At 24 weeks

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=65 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=65 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=68 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Percentage of Participants With a Reduction of Mean GH Levels to < 2.5 µg/L and Normalization of Sex- and Age-adjusted IGF-1.	15.4 percentage of participants Interval 7.63 to 26.48	20.0 percentage of participants Interval 11.1 to 31.77	0 percentage of participants Interval 0.0 to 5.28

SECONDARY outcome

Timeframe: Extension baseline up to approximately week 268

The percentage of patients achieving mean growth hormone (GH) levels \< 2.5 μg/L and normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect GH or IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (extension full analysis set)

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 136	15.8 percentage of participants Interval 7.48 to 27.87	24.1 percentage of participants Interval 13.49 to 37.64	29.0 percentage of participants Interval 18.2 to 41.95
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 160	19.3 percentage of participants Interval 10.05 to 31.91	20.4 percentage of participants Interval 10.63 to 33.53	30.6 percentage of participants Interval 19.56 to 43.65
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 184	17.5 percentage of participants Interval 8.75 to 29.91	20.4 percentage of participants Interval 10.63 to 33.53	17.7 percentage of participants Interval 9.2 to 29.53
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 196	15.8 percentage of participants Interval 7.48 to 27.87	20.4 percentage of participants Interval 10.63 to 33.53	24.2 percentage of participants Interval 14.22 to 36.74
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 232	14.0 percentage of participants Interval 6.26 to 25.79	14.8 percentage of participants Interval 6.62 to 27.12	14.5 percentage of participants Interval 6.86 to 25.78
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 244	14.0 percentage of participants Interval 6.26 to 25.79	7.4 percentage of participants Interval 2.06 to 17.89	11.3 percentage of participants Interval 4.66 to 21.89
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 16	19.3 percentage of participants Interval 10.05 to 31.91	25.9 percentage of participants Interval 14.96 to 39.65	19.4 percentage of participants Interval 10.42 to 31.37
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 28	17.5 percentage of participants Interval 8.75 to 29.91	25.9 percentage of participants Interval 14.96 to 39.65	19.4 percentage of participants Interval 10.42 to 31.37
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 40	21.1 percentage of participants Interval 11.38 to 33.89	27.8 percentage of participants Interval 16.46 to 41.64	17.7 percentage of participants Interval 9.2 to 29.53
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 52	21.1 percentage of participants Interval 11.38 to 33.89	29.6 percentage of participants Interval 17.98 to 43.61	21.0 percentage of participants Interval 11.66 to 33.18
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 64	22.8 percentage of participants Interval 12.74 to 35.84	20.4 percentage of participants Interval 10.63 to 33.53	25.8 percentage of participants Interval 15.53 to 38.5
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 76	21.1 percentage of participants Interval 11.38 to 33.89	29.6 percentage of participants Interval 17.98 to 43.61	27.4 percentage of participants Interval 16.85 to 40.23
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 88	24.6 percentage of participants Interval 14.13 to 37.76	31.5 percentage of participants Interval 19.52 to 45.55	25.8 percentage of participants Interval 15.53 to 38.5
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 100	24.6 percentage of participants Interval 14.13 to 37.76	24.1 percentage of participants Interval 13.49 to 37.64	32.3 percentage of participants Interval 20.94 to 45.34
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 112	24.6 percentage of participants Interval 14.13 to 37.76	25.9 percentage of participants Interval 14.96 to 39.65	25.8 percentage of participants Interval 15.53 to 38.5
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 124	21.1 percentage of participants Interval 11.38 to 33.89	24.1 percentage of participants Interval 13.49 to 37.64	25.8 percentage of participants Interval 15.53 to 38.5
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 148	21.1 percentage of participants Interval 11.38 to 33.89	20.4 percentage of participants Interval 10.63 to 33.53	29.0 percentage of participants Interval 18.2 to 41.95
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 172	22.8 percentage of participants Interval 12.74 to 35.84	20.4 percentage of participants Interval 10.63 to 33.53	21.0 percentage of participants Interval 11.66 to 33.18
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 208	17.5 percentage of participants Interval 8.75 to 29.91	18.5 percentage of participants Interval 9.25 to 31.43	19.4 percentage of participants Interval 10.42 to 31.37
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 220	21.1 percentage of participants Interval 11.38 to 33.89	11.1 percentage of participants Interval 4.19 to 22.63	14.5 percentage of participants Interval 6.86 to 25.78
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 256	10.5 percentage of participants Interval 3.96 to 21.52	7.4 percentage of participants Interval 2.06 to 17.89	3.2 percentage of participants Interval 0.39 to 11.17
Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 268	5.3 percentage of participants Interval 1.1 to 14.62	5.6 percentage of participants Interval 1.16 to 15.39	1.6 percentage of participants Interval 0.04 to 8.66

SECONDARY outcome

Timeframe: Extension baseline up to approximately week 268

The percentage of patients achieving normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set)

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 76	26.3 percentage of participants Interval 15.54 to 39.66	35.2 percentage of participants Interval 22.68 to 49.38	29.0 percentage of participants Interval 18.2 to 41.95
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 88	28.1 percentage of participants Interval 16.97 to 41.54	35.2 percentage of participants Interval 22.68 to 49.38	25.8 percentage of participants Interval 15.53 to 38.5
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 136	21.1 percentage of participants Interval 11.38 to 33.89	25.9 percentage of participants Interval 14.96 to 39.65	37.1 percentage of participants Interval 25.16 to 50.31
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 172	26.3 percentage of participants Interval 15.54 to 39.66	22.2 percentage of participants Interval 12.04 to 35.6	22.6 percentage of participants Interval 12.93 to 34.97
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 184	19.3 percentage of participants Interval 10.05 to 31.91	22.2 percentage of participants Interval 12.04 to 35.6	22.6 percentage of participants Interval 12.93 to 34.97
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 220	22.8 percentage of participants Interval 12.74 to 35.84	11.1 percentage of participants Interval 4.19 to 22.63	19.4 percentage of participants Interval 10.42 to 31.37
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 100	31.6 percentage of participants Interval 19.91 to 45.24	29.6 percentage of participants Interval 17.98 to 43.61	32.3 percentage of participants Interval 20.94 to 45.34
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 112	31.6 percentage of participants Interval 19.91 to 45.24	27.8 percentage of participants Interval 16.46 to 41.64	30.6 percentage of participants Interval 19.56 to 43.65
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 16	33.3 percentage of participants Interval 21.4 to 47.06	29.0 percentage of participants Interval 17.98 to 43.61	25.8 percentage of participants Interval 15.53 to 38.5
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 28	29.8 percentage of participants Interval 18.43 to 43.4	33.3 percentage of participants Interval 21.09 to 47.47	22.6 percentage of participants Interval 12.93 to 34.97
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 40	36.8 percentage of participants Interval 24.45 to 50.66	37.0 percentage of participants Interval 24.29 to 51.26	24.2 percentage of participants Interval 14.22 to 36.74
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 52	28.1 percentage of participants Interval 16.97 to 41.54	33.3 percentage of participants Interval 21.09 to 47.47	25.8 percentage of participants Interval 15.53 to 38.5
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 64	33.3 percentage of participants Interval 21.4 to 47.06	27.8 percentage of participants Interval 16.46 to 41.64	29.0 percentage of participants Interval 18.2 to 41.95
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 124	24.6 percentage of participants Interval 14.13 to 37.76	31.5 percentage of participants Interval 19.52 to 45.55	29.0 percentage of participants Interval 18.2 to 41.95
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 148	26.3 percentage of participants Interval 15.54 to 39.66	22.2 percentage of participants Interval 12.04 to 35.6	33.9 percentage of participants Interval 22.33 to 47.01
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 160	24.6 percentage of participants Interval 14.13 to 37.76	25.9 percentage of participants Interval 14.96 to 39.65	33.9 percentage of participants Interval 22.33 to 47.01
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 196	24.6 percentage of participants Interval 14.13 to 37.76	22.2 percentage of participants Interval 12.04 to 35.6	27.4 percentage of participants Interval 16.85 to 40.23
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 208	22.8 percentage of participants Interval 12.74 to 35.84	22.2 percentage of participants Interval 12.04 to 35.6	21.0 percentage of participants Interval 11.66 to 33.18
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 232	14.0 percentage of participants Interval 6.26 to 25.79	14.8 percentage of participants Interval 6.62 to 27.12	17.7 percentage of participants Interval 9.2 to 29.53
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 244	14.0 percentage of participants Interval 6.26 to 25.79	9.3 percentage of participants Interval 3.08 to 20.3	14.5 percentage of participants Interval 6.86 to 25.78
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 256	12.3 percentage of participants Interval 5.08 to 23.68	7.4 percentage of participants Interval 2.06 to 17.89	6.5 percentage of participants Interval 1.79 to 15.7
Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). Week 268	5.3 percentage of participants Interval 1.1 to 14.62	5.6 percentage of participants Interval 1.16 to 15.39	1.6 percentage of participants Interval 0.04 to 8.66

SECONDARY outcome

Timeframe: Extension baseline up to approximately week 268

Population: Full analysis set (FAS): comprised all patients who were randomized. Following the intent-to-treat principle, patients were analyzed according to the study drug they were assigned to at randomization and actual stratum.

The percentage of patients achieving mean growth hormone (GH) levels \< 2.5 μg/L was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Concomitant medication known to affect GH levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set)

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 28	40.4 percentage of participants Interval 27.56 to 54.18	44.4 percentage of participants Interval 30.92 to 58.6	43.5 percentage of participants Interval 30.99 to 56.74
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 220	29.8 percentage of participants Interval 18.43 to 43.4	18.5 percentage of participants Interval 9.25 to 31.43	22.6 percentage of participants Interval 12.93 to 34.97
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 244	19.3 percentage of participants Interval 10.05 to 31.91	11.1 percentage of participants Interval 4.19 to 22.63	12.9 percentage of participants Interval 5.74 to 23.85
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 16	38.6 percentage of participants Interval 26.0 to 52.43	55.6 percentage of participants Interval 41.4 to 69.08	33.9 percentage of participants Interval 22.33 to 47.01
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 40	38.6 percentage of participants Interval 26.0 to 52.43	42.6 percentage of participants Interval 29.23 to 56.79	40.3 percentage of participants Interval 28.05 to 53.55
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 52	38.6 percentage of participants Interval 26.0 to 52.43	46.3 percentage of participants Interval 32.62 to 60.39	41.9 percentage of participants Interval 29.51 to 55.15
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 64	40.4 percentage of participants Interval 27.56 to 54.18	37.0 percentage of participants Interval 24.29 to 51.26	41.9 percentage of participants Interval 29.51 to 55.15
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 76	33.3 percentage of participants Interval 21.4 to 47.06	44.4 percentage of participants Interval 30.92 to 58.6	45.2 percentage of participants Interval 32.48 to 58.32
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 88	40.4 percentage of participants Interval 27.56 to 54.18	42.6 percentage of participants Interval 29.23 to 56.79	45.2 percentage of participants Interval 32.48 to 58.32
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 100	40.4 percentage of participants Interval 27.56 to 54.18	40.7 percentage of participants Interval 27.57 to 54.97	46.8 percentage of participants Interval 33.98 to 59.88
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 112	36.8 percentage of participants Interval 24.45 to 50.66	44.4 percentage of participants Interval 30.92 to 58.6	40.3 percentage of participants Interval 28.05 to 53.55
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 124	40.4 percentage of participants Interval 27.56 to 54.18	31.5 percentage of participants Interval 19.52 to 45.55	41.9 percentage of participants Interval 29.51 to 55.15
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 136	36.8 percentage of participants Interval 24.45 to 50.66	35.2 percentage of participants Interval 22.68 to 49.38	43.5 percentage of participants Interval 30.99 to 56.74
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 148	40.4 percentage of participants Interval 27.56 to 54.18	33.3 percentage of participants Interval 21.09 to 47.47	43.5 percentage of participants Interval 30.99 to 56.74
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 160	38.6 percentage of participants Interval 26.0 to 52.43	33.3 percentage of participants Interval 21.09 to 47.47	40.3 percentage of participants Interval 28.05 to 53.55
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 172	40.4 percentage of participants Interval 27.56 to 54.18	37.0 percentage of participants Interval 24.29 to 51.26	38.7 percentage of participants Interval 26.6 to 51.93
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 184	33.3 percentage of participants Interval 21.4 to 47.06	31.5 percentage of participants Interval 19.52 to 45.55	33.9 percentage of participants Interval 22.33 to 47.01
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 196	29.8 percentage of participants Interval 18.43 to 43.4	29.6 percentage of participants Interval 17.98 to 43.61	35.5 percentage of participants Interval 23.74 to 48.66
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 208	31.6 percentage of participants Interval 19.91 to 45.24	24.1 percentage of participants Interval 13.49 to 37.64	25.8 percentage of participants Interval 15.53 to 38.5
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 232	24.6 percentage of participants Interval 14.3 to 37.76	18.5 percentage of participants Interval 9.25 to 31.43	21.0 percentage of participants Interval 11.66 to 33.18
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 256	15.8 percentage of participants Interval 7.48 to 27.87	9.3 percentage of participants Interval 3.08 to 20.3	6.5 percentage of participants Interval 1.79 to 15.7
Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 268	7.0 percentage of participants Interval 1.95 to 17.0	5.6 percentage of participants Interval 1.16 to 15.39	3.2 percentage of participants Interval 0.39 to 11.17

SECONDARY outcome

Timeframe: Extension baseline up to approximately week 268

The percentage of patients achieving mean growth hormone (GH) levels \< 1.0 μg/L and normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect GH or IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 16	10.5 Participants Interval 3.96 to 21.52	16.7 Participants Interval 7.92 to 29.29	6.5 Participants Interval 1.79 to 15.7
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 40	10.5 Participants Interval 3.96 to 21.52	9.3 Participants Interval 3.08 to 20.3	4.8 Participants Interval 1.01 to 13.5
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 100	12.3 Participants Interval 5.08 to 23.68	14.8 Participants Interval 6.62 to 27.12	8.1 Participants Interval 2.67 to 17.83
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 136	3.5 Participants Interval 0.43 to 12.11	18.5 Participants Interval 9.25 to 31.43	11.3 Participants Interval 4.66 to 21.89
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 172	14.0 Participants Interval 6.26 to 25.79	13.0 Participants Interval 5.37 to 24.9	8.1 Participants Interval 2.67 to 17.83
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 196	8.8 Participants Interval 2.91 to 19.3	13.0 Participants Interval 5.37 to 24.9	8.1 Participants Interval 2.67 to 17.83
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 208	8.8 Participants Interval 2.91 to 19.3	9.3 Participants Interval 3.08 to 20.3	6.5 Participants Interval 1.79 to 15.7
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 220	10.5 Participants Interval 3.96 to 21.52	7.4 Participants Interval 2.06 to 17.89	6.5 Participants Interval 1.79 to 15.7
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 232	10.5 Participants Interval 3.96 to 21.52	3.7 Participants Interval 0.45 to 12.75	4.8 Participants Interval 1.01 to 13.5
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 244	8.8 Participants Interval 2.91 to 19.3	3.7 Participants Interval 0.45 to 12.75	6.5 Participants Interval 1.79 to 15.7
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 28	8.8 Participants Interval 2.91 to 19.3	14.8 Participants Interval 6.62 to 27.12	8.1 Participants Interval 2.67 to 17.83
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 52	8.8 Participants Interval 2.91 to 19.3	13.0 Participants Interval 5.37 to 24.9	4.8 Participants Interval 1.01 to 13.5
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 64	8.8 Participants Interval 2.91 to 19.3	13.0 Participants Interval 5.37 to 24.9	9.7 Participants Interval 3.63 to 19.88
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 76	10.5 Participants Interval 3.96 to 21.52	13.0 Participants Interval 5.37 to 24.9	6.5 Participants Interval 1.79 to 15.7
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 88	7.0 Participants Interval 1.95 to 17.0	20.4 Participants Interval 10.63 to 33.53	4.8 Participants Interval 1.01 to 13.5
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 112	14.0 Participants Interval 6.26 to 25.79	20.4 Participants Interval 10.63 to 33.53	9.7 Participants Interval 3.63 to 19.88
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 124	7.0 Participants Interval 1.95 to 17.0	14.8 Participants Interval 6.62 to 27.12	8.1 Participants Interval 2.67 to 17.83
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 148	10.5 Participants Interval 3.96 to 21.52	14.8 Participants Interval 6.62 to 27.12	8.1 Participants Interval 2.67 to 17.83
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 160	8.8 Participants Interval 2.91 to 19.3	14.8 Participants Interval 6.62 to 27.12	9.7 Participants Interval 3.63 to 19.88
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 184	7.0 Participants Interval 1.95 to 17.0	13.0 Participants Interval 5.37 to 24.9	3.2 Participants Interval 0.39 to 11.17
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 256	8.8 Participants Interval 2.91 to 19.3	3.7 Participants Interval 0.45 to 12.75	3.2 Participants Interval 0.39 to 11.17
Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 268	1.8 Participants Interval 0.04 to 9.39	3.7 Participants Interval 0.45 to 12.75	1.6 Participants Interval 0.04 to 8.66

SECONDARY outcome

Timeframe: Extension baseline up to approximately week 268

The percentage of patients achieving mean growth hormone (GH) levels \< 1.0 μg/L was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Concomitant medication known to affect GH levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set)

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 16	14.0 percentage of participants Interval 6.26 to 25.79	27.8 percentage of participants Interval 16.46 to 41.64	8.1 percentage of participants Interval 2.67 to 17.83
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 88	15.8 percentage of participants Interval 7.48 to 27.87	22.2 percentage of participants Interval 12.04 to 35.6	11.3 percentage of participants Interval 4.66 to 21.89
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 124	12.3 percentage of participants Interval 5.08 to 23.68	16.7 percentage of participants Interval 7.92 to 29.29	14.5 percentage of participants Interval 6.86 to 25.78
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 160	17.5 percentage of participants Interval 8.75 to 29.91	18.5 percentage of participants Interval 9.25 to 31.43	14.5 percentage of participants Interval 6.86 to 25.78
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 184	17.5 percentage of participants Interval 8.75 to 29.91	18.5 percentage of participants Interval 9.25 to 31.43	6.5 percentage of participants Interval 1.79 to 15.7
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 28	14.0 percentage of participants Interval 6.26 to 25.79	22.2 percentage of participants Interval 12.04 to 35.6	9.7 percentage of participants Interval 3.63 to 19.88
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 40	14.0 percentage of participants Interval 6.26 to 25.79	13.0 percentage of participants Interval 5.37 to 24.9	4.8 percentage of participants Interval 1.01 to 13.5
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 52	12.3 percentage of participants Interval 5.08 to 23.68	22.2 percentage of participants Interval 12.04 to 35.6	9.7 percentage of participants Interval 3.63 to 19.88
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 64	15.8 percentage of participants Interval 7.48 to 27.87	18.5 percentage of participants Interval 9.25 to 31.43	11.3 percentage of participants Interval 4.66 to 21.89
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 76	12.3 percentage of participants Interval 5.08 to 23.68	22.2 percentage of participants Interval 12.04 to 35.6	11.3 percentage of participants Interval 4.66 to 21.89
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 100	17.5 percentage of participants Interval 8.75 to 29.91	20.4 percentage of participants Interval 10.63 to 33.53	17.7 percentage of participants Interval 9.2 to 29.53
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 112	17.5 percentage of participants Interval 8.75 to 29.91	25.9 percentage of participants Interval 14.96 to 39.65	16.1 percentage of participants Interval 8.02 to 27.67
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 136	8.8 percentage of participants Interval 2.91 to 19.3	25.9 percentage of participants Interval 14.96 to 39.65	14.5 percentage of participants Interval 6.86 to 25.78
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 148	14.0 percentage of participants Interval 6.26 to 25.79	16.7 percentage of participants Interval 7.92 to 29.29	14.5 percentage of participants Interval 6.86 to 25.78
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 172	17.5 percentage of participants Interval 8.75 to 29.91	14.8 percentage of participants Interval 6.62 to 27.12	14.5 percentage of participants Interval 6.86 to 25.78
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 196	15.8 percentage of participants Interval 7.48 to 27.87	13.0 percentage of participants Interval 5.37 to 24.9	12.9 percentage of participants Interval 5.74 to 23.85
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 208	17.5 percentage of participants Interval 8.75 to 29.91	13.0 percentage of participants Interval 5.37 to 24.9	9.7 percentage of participants Interval 3.63 to 19.88
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 220	15.8 percentage of participants Interval 7.48 to 27.87	11.1 percentage of participants Interval 4.19 to 22.63	9.7 percentage of participants Interval 3.63 to 19.88
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 232	15.8 percentage of participants Interval 7.48 to 27.87	3.7 percentage of participants Interval 0.45 to 12.75	8.1 percentage of participants Interval 2.67 to 17.83
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 244	12.3 percentage of participants Interval 5.08 to 23.68	5.6 percentage of participants Interval 1.16 to 15.39	8.1 percentage of participants Interval 2.67 to 17.83
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 256	12.3 percentage of participants Interval 5.08 to 23.68	3.7 percentage of participants Interval 0.45 to 12.75	4.8 percentage of participants Interval 1.01 to 13.5
Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) Week 268	3.5 percentage of participants Interval 0.43 to 12.11	3.7 percentage of participants Interval 0.45 to 12.75	1.6 percentage of participants Interval 0.04 to 8.66

SECONDARY outcome

Timeframe: CORE baseline up to approximately 24 weeks

Population: Number analyzed is based on available data at specific visits

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set) Week 12 - CORE	-0.8 mcg/L Standard Deviation 29.77	-6.4 mcg/L Standard Deviation 14.35	—
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set) Week 24 - CORE	-0.6 mcg/L Standard Deviation 32.38	-7.2 mcg/L Standard Deviation 15.19	—

SECONDARY outcome

Timeframe: CORE and extension baseline up to approximately 268 weeks

Population: Available data for analysis differed from visit to visit

Change from CORE baseline at each scheduled assessment was performed for patients randomized to pasireotide arms. Change from extension baseline at each scheduled assessment was performed for patients randomized to active control arm.

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 124 - extension	-5.5 mcg/L Standard Deviation 5.85	-6.0 mcg/L Standard Deviation 6.26	-4.0 mcg/L Standard Deviation 4.36
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 136 - extension	-6.0 mcg/L Standard Deviation 6.59	-5.3 mcg/L Standard Deviation 4.99	-4.0 mcg/L Standard Deviation 4.44
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 16 - extension	-7.9 mcg/L Standard Deviation 24.90	-6.9 mcg/L Standard Deviation 14.88	-8.4 mcg/L Standard Deviation 49.64
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 28 - extension	-9.0 mcg/L Standard Deviation 24.21	-4.5 mcg/L Standard Deviation 4.12	-3.0 mcg/L Standard Deviation 3.86
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 40 - extension	-9.7 mcg/L Standard Deviation 25.40	-5.8 mcg/L Standard Deviation 13.93	-11.2 mcg/L Standard Deviation 58.28
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 52 - extension	-10.7 mcg/L Standard Deviation 26.60	-7.1 mcg/L Standard Deviation 17.08	-2.5 mcg/L Standard Deviation 3.02
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 64 - extension	-11.3 mcg/L Standard Deviation 28.37	-7.9 mcg/L Standard Deviation 17.30	-15.7 mcg/L Standard Deviation 76.06
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 76 - extension	-5.5 mcg/L Standard Deviation 5.96	-7.2 mcg/L Standard Deviation 16.16	-3.5 mcg/L Standard Deviation 4.27
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 88 - extension	-5.7 mcg/L Standard Deviation 6.21	-6.2 mcg/L Standard Deviation 8.55	-3.6 mcg/L Standard Deviation 3.22
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 100 - extension	-5.6 mcg/L Standard Deviation 5.71	-5.3 mcg/L Standard Deviation 5.06	-3.8 mcg/L Standard Deviation 4.28
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 112 - extension	-5.8 mcg/L Standard Deviation 6.03	-4.4 mcg/L Standard Deviation 6.57	-3.9 mcg/L Standard Deviation 5.13
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 148 - extension	-6.3 mcg/L Standard Deviation 6.21	6.1 mcg/L Standard Deviation 6.28	-3.8 mcg/L Standard Deviation 3.11
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 160 - extension	-5.5 mcg/L Standard Deviation 4.70	-4.9 mcg/L Standard Deviation 5.33	-3.2 mcg/L Standard Deviation 2.25
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 172 - extension	-6.3 mcg/L Standard Deviation 6.34	-5.9 mcg/L Standard Deviation 5.97	-3.0 mcg/L Standard Deviation 2.47
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 184 - extension	-6.3 mcg/L Standard Deviation 5.44	-5.8 mcg/L Standard Deviation 5.79	-3.3 mcg/L Standard Deviation 2.31
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 196 - extension	-7.1 mcg/L Standard Deviation 6.81	-6.5 mcg/L Standard Deviation 7.17	-3.4 mcg/L Standard Deviation 2.71
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 208 - extension (n=22,20,23)	-7.0 mcg/L Standard Deviation 6.82	-6.2 mcg/L Standard Deviation 6.22	-3.5 mcg/L Standard Deviation 2.50
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 220 - extension	-7.1 mcg/L Standard Deviation 6.91	-7.1 mcg/L Standard Deviation 8.12	-3.8 mcg/L Standard Deviation 2.48
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 232 - extension	-5.7 mcg/L Standard Deviation 5.46	-6.8 mcg/L Standard Deviation 8.10	-4.2 mcg/L Standard Deviation 2.46
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 244 - extension	-6.0 mcg/L Standard Deviation 6.03	-2.4 mcg/L Standard Deviation 0.90	-4.2 mcg/L Standard Deviation 2.58
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 256 - extension	-6.4 mcg/L Standard Deviation 5.91	-4.9 mcg/L Standard Deviation 3.49	-5.0 mcg/L Standard Deviation 3.26
Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 268 - extension	-3.6 mcg/L Standard Deviation 1.58	-2.5 mcg/L Standard Deviation 0.57	-3.7 mcg/L Standard Deviation 2.23

SECONDARY outcome

Timeframe: CORE baseline up to approximately 24 weeks

Population: Available data for analysis varies from visit to visit

Standardized IGF-1 = IGF-1 value / ULN, where ULN is the upper limit of the normal range

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set) CORE Week 12	0.7 mcg/L Standard Deviation 0.97	-1.1 mcg/L Standard Deviation 1.03	—
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set) CORE Week 24	-0.7 mcg/L Standard Deviation 0.97	-1.1 mcg/L Standard Deviation 1.12	—

SECONDARY outcome

Timeframe: CORE and extension baseline up to approximately 268 weeks

Population: Available data for analysis differed from visit to visit

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 100 extension	-1.4 mcg/L Standard Deviation 0.93	-1.5 mcg/L Standard Deviation 0.95	-1.3 mcg/L Standard Deviation 0.92
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 112 extension	-1.5 mcg/L Standard Deviation 0.87	-1.5 mcg/L Standard Deviation 1.00	-1.4 mcg/L Standard Deviation 0.89
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 124 extension	-1.4 mcg/L Standard Deviation 0.86	-1.5 mcg/L Standard Deviation 0.95	-1.3 mcg/L Standard Deviation 0.97
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 136 extension	-1.4 mcg/L Standard Deviation 0.91	-1.7 mcg/L Standard Deviation 0.92	-1.4 mcg/L Standard Deviation 0.86
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 148 extension	-1.4 mcg/L Standard Deviation 0.86	-1.5 mcg/L Standard Deviation 0.99	-1.3 mcg/L Standard Deviation 0.84
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 160 extension	-1.4 mcg/L Standard Deviation 0.90	-1.6 mcg/L Standard Deviation 0.87	-1.4 mcg/L Standard Deviation 0.94
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 172 extension	-1.5 mcg/L Standard Deviation 0.81	-1.6 mcg/L Standard Deviation 0.97	-1.3 mcg/L Standard Deviation 0.98
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 184 extension	-1.3 mcg/L Standard Deviation 0.70	-1.5 mcg/L Standard Deviation 1.03	-1.4 mcg/L Standard Deviation 0.93
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 16 extension	-0.8 mcg/L Standard Deviation 0.99	-1.4 mcg/L Standard Deviation 0.97	-0.9 mcg/L Standard Deviation 0.81
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 28 extension	-0.9 mcg/L Standard Deviation 1.00	-1.3 mcg/L Standard Deviation 1.13	-0.9 mcg/L Standard Deviation 0.88
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 40 extension	-1.1 mcg/L Standard Deviation 0.95	-1.4 mcg/L Standard Deviation 0.94	-1.1 mcg/L Standard Deviation 0.91
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 52 extension	-1.1 mcg/L Standard Deviation 0.90	-1.3 mcg/L Standard Deviation 0.95	-1.1 mcg/L Standard Deviation 0.95
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 64 extension	-1.3 mcg/L Standard Deviation 0.99	-1.4 mcg/L Standard Deviation 0.98	-1.3 mcg/L Standard Deviation 0.81
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 76 extension	-1.3 mcg/L Standard Deviation 0.87	-1.5 mcg/L Standard Deviation 0.94	-1.3 mcg/L Standard Deviation 0.84
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 88 extension	-1.3 mcg/L Standard Deviation 0.80	-1.6 mcg/L Standard Deviation 1.01	-1.3 mcg/L Standard Deviation 0.90
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 196 extension	-1.4 mcg/L Standard Deviation 0.81	-1.5 mcg/L Standard Deviation 1.11	-1.3 mcg/L Standard Deviation 1.11
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 208 extension	-1.4 mcg/L Standard Deviation 0.79	-1.6 mcg/L Standard Deviation 1.00	-1.2 mcg/L Standard Deviation 0.98
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 220 extension	-1.4 mcg/L Standard Deviation 0.94	-1.6 mcg/L Standard Deviation 1.06	-1.4 mcg/L Standard Deviation 0.91
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 232 extension	-1.4 mcg/L Standard Deviation 0.92	-1.5 mcg/L Standard Deviation 1.13	-1.7 mcg/L Standard Deviation 0.82
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 244 extension	-1.3 mcg/L Standard Deviation 0.75	-1.9 mcg/L Standard Deviation 1.12	-1.5 mcg/L Standard Deviation 0.79
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 256 extension	-1.3 mcg/L Standard Deviation 0.58	-1.4 mcg/L Standard Deviation 1.39	-1.8 mcg/L Standard Deviation 0.90
Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 268 extension	-1.4 mcg/L Standard Deviation 0.43	-1.7 mcg/L Standard Deviation 0.39	-1.7 mcg/L Standard Deviation 0.81

SECONDARY outcome

Timeframe: CORE baseline up to approximately 268 weeks

n is the number of patients achieving response criteria. The weeks correspond to duration of first response (in weeks) for patients achieving biomedical control. Median and 95% CI are derived from Kaplan-Meier curves. Kaplan-Meier estimates \[95% CI\] at each time point are estimates of probability of response.

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Duration of the First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)	29.1 weeks Interval 15.6 to 48.1	26.9 weeks Interval 12.7 to 48.0	24.9 weeks Interval 12.4 to 47.4

SECONDARY outcome

Timeframe: CORE baseline up to approximately 268 weeks

Time to first response is defined as the time from the date of first dose to the date of first occurrence of a reduction of mean GH \< 2.5 µg/L and the normalization of IGF-1. The weeks correspond to time taken to achieve first mean GH \< 2.5 µg/L and the normalization of IGF-1.

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Time to First Response (Weeks) by Treatment for Patients Achieving a Reduction of Mean GH Level to < 2.5 µg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly	112.3 weeks Interval 76.1 to 254.1	65.3 weeks Interval 40.4 to 94.9	95.1 weeks Interval 65.3 to 156.0

SECONDARY outcome

Timeframe: CORE baseline up to approximately 24 weeks

Population: Available data available for analysis differed from visit to visit

Acromegaly Quality of Life questionnaire (AcroQoL) is a validated disease specific questionnaire. It contains 22 items divided into two scales: physical aspects (8 items) and psychological aspects (14 items) which is divided in two sub-scales: physical appearance and personal relationships of the patient (seven items each). The total score and sub-scores were calculated using the following formula: ((X -Y) / 4Y) x 100, X=sum of the scores for individual items (between 1 and 5 for each item), Y=number of individual items included in above sum (i.e. 22 for the total score, 8 for the physical sub-score, 14 for the psychological sub-score, 7 for the sub-score 'appearance' and 'personal relations'). 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. If more than 25% of items are not completed, results were considered invalid.

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set) Week 4 CORE	3.5 scores on a scale Standard Deviation 11.28	2.3 scores on a scale Standard Deviation 11.08	—
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set) Week 8 CORE	2.4 scores on a scale Standard Deviation 12.97	2.5 scores on a scale Standard Deviation 12.11	—
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set) Week 12 CORE	3.0 scores on a scale Standard Deviation 12.41	1.9 scores on a scale Standard Deviation 11.50	—
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set) Week 16 CORE	3.3 scores on a scale Standard Deviation 12.99	6.6 scores on a scale Standard Deviation 15.33	—
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set) Week 20 CORE	3.5 scores on a scale Standard Deviation 12.89	4.0 scores on a scale Standard Deviation 16.02	—
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set) Week24 CORE	3.0 scores on a scale Standard Deviation 16.61	5.4 scores on a scale Standard Deviation 17.77	—

SECONDARY outcome

Timeframe: CORE Baseline and extension baseline up to approximately 268 weeks

Population: completed and valid questionnaires at visits

Outcome measures

SECONDARY outcome

Timeframe: Extension baseline up to approximately 196 weeks

Population: Available data for analysis varies at visits

PK samples were collected for those patients treated with pasireotide LAR in the core study and who continued on pasireotide LAR in the extension phase. PK samples were collected before the injection of pasireotide LAR only at weeks 112 and 196. PK samples were also collected at weeks 48 and 132 only for all patients treated with octreotide LAR 30 mg or lanreotide ATG 120 mg in the core study who started treatment with pasireotide LAR in the extension study. Blood samples (2.5 mL each sample) were collected to yield 1-mL plasma for analysis of pasireotide LAR oncentration.

Outcome measures

Outcome measures
Measure	Pasireotide LAR 40 mg n=116 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=93 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Summary of Pasireotide Trough Concentrations in Acromegaly Patients Following Monthly i.m. Injections of Pasireotide LAR by Incident Dose From Start of Extension Phase up to Week 196 of the Extension Phase (PK Set) Week 48	5.70 mL Standard Deviation 3.159	—	—
Summary of Pasireotide Trough Concentrations in Acromegaly Patients Following Monthly i.m. Injections of Pasireotide LAR by Incident Dose From Start of Extension Phase up to Week 196 of the Extension Phase (PK Set) Week 112	8.66 mL Standard Deviation 4.154	14.06 mL Standard Deviation 9.807	—
Summary of Pasireotide Trough Concentrations in Acromegaly Patients Following Monthly i.m. Injections of Pasireotide LAR by Incident Dose From Start of Extension Phase up to Week 196 of the Extension Phase (PK Set) Week 132	9.28 mL Standard Deviation 5.067	—	—
Summary of Pasireotide Trough Concentrations in Acromegaly Patients Following Monthly i.m. Injections of Pasireotide LAR by Incident Dose From Start of Extension Phase up to Week 196 of the Extension Phase (PK Set) Week 196	10.32 mL Standard Deviation 5.473	14.96 mL Standard Deviation 10.210	—

Adverse Events

Pasireotide LAR 40 mg

Serious events: 18 serious events

Other events: 59 other events

Deaths: 2 deaths

Pasireotide LAR 60 mg

Serious events: 14 serious events

Other events: 58 other events

Deaths: 0 deaths

Cross-over to Pasireotide

Serious events: 20 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Pasireotide LAR 40 mg n=57 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Pasireotide LAR 60 mg n=54 Participants Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days	Control Arm (Octreotide or Lanreotide) n=62 Participants Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 16 extension	4.2 scores on a scale Standard Deviation 16.34	2.9 scores on a scale Standard Deviation 19.09	0.8 scores on a scale Standard Deviation 10.22
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 28 extension	5.6 scores on a scale Standard Deviation 13.21	4.8 scores on a scale Standard Deviation 16.83	3.3 scores on a scale Standard Deviation 10.70
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 40 extension	3.2 scores on a scale Standard Deviation 15.78	2.5 scores on a scale Standard Deviation 18.21	3.2 scores on a scale Standard Deviation 10.31
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 52 extension	6.1 scores on a scale Standard Deviation 14.28	5.7 scores on a scale Standard Deviation 18.69	4.2 scores on a scale Standard Deviation 11.01
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 64 extension	5.8 scores on a scale Standard Deviation 13.65	4.2 scores on a scale Standard Deviation 18.89	5.4 scores on a scale Standard Deviation 12.12
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 76 extension	7.7 scores on a scale Standard Deviation 14.93	2.5 scores on a scale Standard Deviation 19.30	7.7 scores on a scale Standard Deviation 15.17
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 88 extension	4.6 scores on a scale Standard Deviation 15.11	5.6 scores on a scale Standard Deviation 18.08	6.4 scores on a scale Standard Deviation 10.29
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 100 extension	4.3 scores on a scale Standard Deviation 14.80	3.9 scores on a scale Standard Deviation 16.91	5.9 scores on a scale Standard Deviation 11.13
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 112 extension	4.6 scores on a scale Standard Deviation 15.83	6.5 scores on a scale Standard Deviation 18.36	4.1 scores on a scale Standard Deviation 10.35
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 124 extension	5.8 scores on a scale Standard Deviation 16.46	2.0 scores on a scale Standard Deviation 17.95	2.0 scores on a scale Standard Deviation 10.97
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 136 extension	7.5 scores on a scale Standard Deviation 18.72	5.4 scores on a scale Standard Deviation 16.73	6.5 scores on a scale Standard Deviation 11.82
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 148 extension	7.6 scores on a scale Standard Deviation 18.56	6.8 scores on a scale Standard Deviation 16.65	5.5 scores on a scale Standard Deviation 12.95
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 160 extension	7.0 scores on a scale Standard Deviation 19.10	5.1 scores on a scale Standard Deviation 15.70	1.5 scores on a scale Standard Deviation 13.36
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 172 extension	4.8 scores on a scale Standard Deviation 17.97	5.7 scores on a scale Standard Deviation 17.52	2.1 scores on a scale Standard Deviation 12.13
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 184 extension	5.8 scores on a scale Standard Deviation 15.31	5.8 scores on a scale Standard Deviation 16.83	1.6 scores on a scale Standard Deviation 12.45
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 196 extension	6.1 scores on a scale Standard Deviation 16.94	6.0 scores on a scale Standard Deviation 18.58	3.8 scores on a scale Standard Deviation 13.11
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 208 extension	1.2 scores on a scale Standard Deviation 13.27	6.2 scores on a scale Standard Deviation 17.31	4.5 scores on a scale Standard Deviation 12.62
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 220 extension	4.8 scores on a scale Standard Deviation 21.99	5.8 scores on a scale Standard Deviation 17.12	7.3 scores on a scale Standard Deviation 16.28
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 232 extension	2.1 scores on a scale Standard Deviation 17.51	-0.2 scores on a scale Standard Deviation 16.73	7.0 scores on a scale Standard Deviation 15.15
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 244 extension	4.5 scores on a scale Standard Deviation 20.06	6.3 scores on a scale Standard Deviation 11.05	3.0 scores on a scale Standard Deviation 18.65
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 256 extension	6.1 scores on a scale Standard Deviation 25.91	-3.0 scores on a scale Standard Deviation 7.07	0.3 scores on a scale Standard Deviation 14.08
Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) Week 268 extension	0.6 scores on a scale Standard Deviation 16.74	-4.9 scores on a scale Standard Deviation 4.30	-10.6 scores on a scale Standard Deviation 7.57