Trial Outcomes & Findings for Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues (NCT NCT02354508)

Results Overview

Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

123 participants

Primary outcome timeframe

Week 36

Results posted on

2019-12-10

Participant Flow

Planned 112 participants and analyzed 123 participants. For Participant Flow/Baseline Characteristics Tables, Total = Participants in the Pasireotide LAR arm.

Participants were allocated to Group 1 or Group 2 based on previously received first generation Somatostatin analog (SSA).

Participant milestones

Participant milestones
Measure	Lanreotide 120 mg Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).
Period 1: Core Phase STARTED	41	29	53
Period 1: Core Phase COMPLETED	39	27	47
Period 1: Core Phase NOT COMPLETED	2	2	6
Period 2: Extension Phase STARTED	26	23	39
Period 2: Extension Phase COMPLETED	20	19	36
Period 2: Extension Phase NOT COMPLETED	6	4	3
Period 3: Post-treatment Follow up Phase STARTED	26	23	39
Period 3: Post-treatment Follow up Phase Entered Post-treatment f/up Discontinued	4	3	3
Period 3: Post-treatment Follow up Phase COMPLETED	22	20	36
Period 3: Post-treatment Follow up Phase NOT COMPLETED	4	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Lanreotide 120 mg Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).
Period 1: Core Phase Adverse Event	1	1	2
Period 1: Core Phase Unsatisfactory therapeutic effect	1	0	2
Period 1: Core Phase Withdrawal by Subject	0	1	2
Period 2: Extension Phase Unsatisfactory therapeutic effect	1	3	2
Period 2: Extension Phase Withdrawal by Subject	0	1	0
Period 2: Extension Phase Physician Decision	5	0	1
Period 3: Post-treatment Follow up Phase Unsatisfactory therapeutic effect	1	2	2
Period 3: Post-treatment Follow up Phase Withdrawal by Subject	0	1	0
Period 3: Post-treatment Follow up Phase Physician Decision	3	0	1

Baseline Characteristics

Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lanreotide 120 mg n=41 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=29 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=53 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Total n=123 Participants Total of all reporting groups
Age, Continuous	41.8 years STANDARD_DEVIATION 10.02 • n=5 Participants	41.6 years STANDARD_DEVIATION 12.89 • n=7 Participants	46.6 years STANDARD_DEVIATION 11.63 • n=5 Participants	43.8 years STANDARD_DEVIATION 11.60 • n=4 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	18 Participants n=7 Participants	25 Participants n=5 Participants	62 Participants n=4 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	11 Participants n=7 Participants	28 Participants n=5 Participants	61 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	34 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants	78 Participants n=4 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized Native American	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants	30 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 36

Population: Full Analysis Set (FAS) comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study.

Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=41 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=29 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=53 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall n=123 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall	14.6 Percentage of participants Interval 5.57 to 29.17	13.8 Percentage of participants Interval 3.89 to 31.66	15.1 Percentage of participants Interval 6.75 to 27.59	14.6 Percentage of participants Interval 8.91 to 22.14	—	—

PRIMARY outcome

Timeframe: Week 36

Population: Full Analysis Set (FAS) comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study. For these patients the Pasireotide LAR dose was uptitrated to 60 mg before Week 36.

Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, for participants who had been up-titrated with pasireotide LAR 60 mg.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=90 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 for Participants Up-titrated to Pasireotide LAR 60 mg	6.7 Percentage of participants Interval 2.49 to 13.95	—	—	—	—	—

PRIMARY outcome

Timeframe: Wek 36

Population: Per-Protocol Set (PPS): consisted of a subset of the patients in the FAS who were compliant with requirements of the clinical study protocol. The protocol deviations criteria were defined prior to database lock. Per-protocol analysis was performed during the core phase, but not during the extension phase.

Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=102 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36	15.7 Percentage of participants Interval 9.24 to 24.22	—	—	—	—	—

PRIMARY outcome

Timeframe: Week 36

Population: Full Analysis Set (FAS) comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study.

Percentage of patients who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, by previous treatment, type of therapy and overall.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=26 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=23 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=39 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall n=76 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication n=12 Participants Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall n=88 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36	7.7 Percentage of participants Interval 0.95 to 25.13	13.0 Percentage of participants Interval 2.78 to 33.59	20.5 Percentage of participants Interval 9.3 to 36.46	17.1 Percentage of participants Interval 9.43 to 27.47	0.0 Percentage of participants Interval 0.0 to 26.46	14.8 Percentage of participants Interval 8.11 to 23.94

PRIMARY outcome

Timeframe: Week 36

Population: Full Analysis Set (FAS) comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study. For these patients the Pasireotide LAR dose was uptitrated to 60 mg any time during the study.

Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, for participants who had been up-titrated with pasireotide LAR 60 mg.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=70 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 for Participants Up-titrated to Pasireotide LAR 60 mg	5.9 Percentage of participants Interval 1.63 to 14.38	—	—	—	—	—

PRIMARY outcome

Timeframe: Week 36

Population: Full Analysis Set (FAS) comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study.

Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, overall by baseline diabetic status.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=88 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 Overall by Baseline Diabetic Status Diabetic	14.0 Percentage of participants Interval 5.3 to 27.93	—	—	—	—	—
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 Overall by Baseline Diabetic Status Pre-diabetic	19.4 Percentage of participants Interval 8.19 to 36.02	—	—	—	—	—
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 Overall by Baseline Diabetic Status Non-diabetic	0.0 Percentage of participants Interval 0.0 to 33.63	—	—	—	—	—

PRIMARY outcome

Timeframe: Week 36

Population: Full Analysis Set (FAS) comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study.

Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, by previous treatment and overall - last observation carried forward (LOCF)

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=41 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=29 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=53 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall n=123 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall - LOCF	14.6 Percentage of participants Interval 5.57 to 29.17	13.8 Percentage of participants Interval 3.89 to 31.66	17.0 Percentage of participants Interval 8.07 to 29.8	15.4 Percentage of participants Interval 9.56 to 23.07	—	—

SECONDARY outcome

Timeframe: Baseline, week 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study.

Core phase - Changes in mean GH from study baseline to week 36.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=41 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=29 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=53 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall n=123 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Change in Mean Growth Hormone (GH) Values From Baseline to Week 36	-7.7 percentage change Standard Deviation 19.51	-8.5 percentage change Standard Deviation 24.41	-2.9 percentage change Standard Deviation 4.21	-6.0 percentage change Standard Deviation 17.10	—	—

SECONDARY outcome

Timeframe: Baseline, week 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study.

Core phase - Changes in standardized IGF-1 from study baseline to week 36.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=41 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=29 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=53 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall n=123 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Change in Standardized IGF-1 Values From Baseline to Week 36	-1.1 percentage change Standard Deviation 1.18	-0.8 percentage change Standard Deviation 0.78	-1.1 percentage change Standard Deviation 1.39	-1.0 percentage change Standard Deviation 1.18	—	—

SECONDARY outcome

Timeframe: Week 12, Week 24, Week 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study.

Percentage of participants achieving GH \<1 μg/L and IGF-1 \<ULN at weeks 12 and 24 overall and by GH level at screening.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=17 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=123 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Week 12: GH: ≥ 1 - ≤ 2.5 μg/L @ screening	25.0 Percentage of participants Interval 0.63 to 80.59	28.6 Percentage of participants Interval 13.22 to 48.67	—	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Week 24: GH: ≥ 1 - ≤ 2.5 μg/L @ screening	25.0 Percentage of participants Interval 0.63 to 80.59	39.3 Percentage of participants Interval 21.5 to 59.42	—	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Week 36: GH: ≥ 1 - ≤ 2.5 μg/L @ screening	25.0 Percentage of participants Interval 0.63 to 80.59	42.9 Percentage of participants Interval 24.46 to 62.82	—	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Week 12: GH: > 2.5 μg/L @ screening	7.7 Percentage of participants Interval 0.19 to 36.03	5.3 Percentage of participants Interval 1.75 to 11.98	—	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Week 24: GH: > 2.5 μg/L @ screening	7.7 Percentage of participants Interval 0.19 to 36.03	5.3 Percentage of participants Interval 1.75 to 11.98	—	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Week 36: GH: > 2.5 μg/L @ screening	7.7 Percentage of participants Interval 0.19 to 36.03	6.4 Percentage of participants Interval 2.38 to 13.38	—	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Week 12: GH: Missing	—	0.0 Percentage of participants Interval 0.0 to 97.5	—	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Week 24: GH: Missing	—	0.0 Percentage of participants Interval 0.0 to 97.5	—	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Week 36: GH: Missing	—	0.0 Percentage of participants Interval 0.0 to 97.5	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 12, 24 & 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study

Percentage of participants achieving IGF-1 \<ULN at weeks 12, 24 \& 36.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=28 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=94 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=1 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall n=123 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With IGF-1 <ULN Overall by GH Level at Screening Week 12	35.7 Percentage of participants Interval 18.64 to 55.93	16.0 Percentage of participants Interval 9.22 to 24.95	0.0 Percentage of participants Interval 0.0 to 97.5	20.3 Percentage of participants Interval 13.61 to 28.52	—	—
Core Phase: Percentage of Participants With IGF-1 <ULN Overall by GH Level at Screening Week 24	42.9 Percentage of participants Interval 24.46 to 62.82	23.4 Percentage of participants Interval 15.29 to 33.26	0.0 Percentage of participants Interval 0.0 to 97.5	27.6 Percentage of participants Interval 19.96 to 36.43	—	—
Core Phase: Percentage of Participants With IGF-1 <ULN Overall by GH Level at Screening Week 36	50.0 Percentage of participants Interval 30.65 to 69.35	25.5 Percentage of participants Interval 17.09 to 35.57	0.0 Percentage of participants Interval 0.0 to 97.5	30.9 Percentage of participants Interval 22.88 to 39.86	—	—

SECONDARY outcome

Timeframe: Weeks 12, 24 & 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study.

Core phase - Percentage of patients achieving GH \<1μg/L at week 12, 24, 36 overall and by GH level at screening.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=52 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=60 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=11 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Overall by Baseline Diabetic Status Week 12	13.5 Percentage of participants Interval 5.59 to 25.79	10.0 Percentage of participants Interval 3.76 to 20.51	0.0 Percentage of participants Interval 0.0 to 28.49	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Overall by Baseline Diabetic Status Week 24	13.5 Percentage of participants Interval 5.59 to 25.79	13.3 Percentage of participants Interval 5.94 to 24.59	9.1 Percentage of participants Interval 0.23 to 41.28	—	—	—
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Overall by Baseline Diabetic Status Week 36	15.4 Percentage of participants Interval 6.88 to 28.08	16.7 Percentage of participants Interval 8.29 to 28.52	0.0 Percentage of participants Interval 0.0 to 28.49	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24 & 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study

Evaluation of effect of pasireotide LAR on Health Related Quality of Life (HRQoL) was assessed using AcroQoL, an acromegaly-specific quality of life instrument. The AcroQol instrument is comprised of 22 questions divided into two scales: one evaluating physical aspects (8 items) and the other that addresses psychological aspects (14 items). The psychological scale can also be further divided into subscale that evaluates physical appearance and the other subscale focused on the impact of the disease on personal relationships of the patient (7 items each). Each of the questions has a 5-item Likert scale. For each dimension the scores range from 0-4 with 0 being the lowest impact and 4 being the most severe.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=123 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=123 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=123 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall n=123 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication n=123 Participants Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL) Week 12	4.5 scores on a scale Standard Deviation 9.52	5.3 scores on a scale Standard Deviation 12.93	4.1 scores on a scale Standard Deviation 10.05	6.5 scores on a scale Standard Deviation 12.43	1.9 scores on a scale Standard Deviation 12.04	—
Core Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL) Week 24	4.7 scores on a scale Standard Deviation 9.88	5.8 scores on a scale Standard Deviation 12.26	4.0 scores on a scale Standard Deviation 10.72	7.2 scores on a scale Standard Deviation 14.44	0.9 scores on a scale Standard Deviation 10.70	—
Core Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL) Week 36	4.6 scores on a scale Standard Deviation 10.14	5.4 scores on a scale Standard Deviation 13.00	4.3 scores on a scale Standard Deviation 11.02	7.0 scores on a scale Standard Deviation 15.33	1.8 scores on a scale Standard Deviation 10.69	—

SECONDARY outcome

Timeframe: Weeks 12, 24 & 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study

Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=123 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=123 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=123 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall n=123 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication n=123 Participants Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 12: Severe	0.8 Percentage of participants	8.9 Percentage of participants	3.3 Percentage of participants	8.9 Percentage of participants	4.9 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 12: Not done	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 24: Mild	27.6 Percentage of participants	20.3 Percentage of participants	21.1 Percentage of participants	26.8 Percentage of participants	13.8 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 24: Severe	1.6 Percentage of participants	7.3 Percentage of participants	1.6 Percentage of participants	3.3 Percentage of participants	0.8 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 24: Not done	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 36: Mild	17.1 Percentage of participants	23.6 Percentage of participants	18.7 Percentage of participants	26.8 Percentage of participants	14.6 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 36: Severe	1.6 Percentage of participants	4.9 Percentage of participants	4.1 Percentage of participants	3.3 Percentage of participants	1.6 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 36: Not done	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 12: Moderate	14.6 Percentage of participants	18.7 Percentage of participants	8.1 Percentage of participants	14.6 Percentage of participants	5.7 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 12: Non/absent	56.9 Percentage of participants	37.4 Percentage of participants	56.9 Percentage of participants	43.1 Percentage of participants	69.1 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 12: Mild	24.4 Percentage of participants	26.8 Percentage of participants	26.8 Percentage of participants	27.6 Percentage of participants	15.4 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 12: Very severe	0.0 Percentage of participants	4.9 Percentage of participants	1.6 Percentage of participants	2.4 Percentage of participants	1.6 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 24: Non/absent	59.3 Percentage of participants	46.3 Percentage of participants	64.2 Percentage of participants	47.2 Percentage of participants	72.4 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 24: Moderate	8.1 Percentage of participants	17.9 Percentage of participants	8.9 Percentage of participants	14.6 Percentage of participants	7.3 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 24: Very severe	0.0 Percentage of participants	4.9 Percentage of participants	0.8 Percentage of participants	4.9 Percentage of participants	2.4 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 36: Non/absent	63.4 Percentage of participants	47.2 Percentage of participants	61.8 Percentage of participants	47.2 Percentage of participants	69.1 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 36: Moderate	9.8 Percentage of participants	13.0 Percentage of participants	7.3 Percentage of participants	12.2 Percentage of participants	5.7 Percentage of participants	—
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms Week 36: Very severe	0.0 Percentage of participants	3.3 Percentage of participants	0.0 Percentage of participants	2.4 Percentage of participants	0.8 Percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 12, 24 & 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study

Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=123 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg n=123 Participants Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg n=123 Participants Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall n=123 Participants This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication n=123 Participants Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline BL: Mild	25.2 Percentage of participants	17.8 Percentage of participants	25.2 Percentage of participants	21.1 Percentage of participants	25.2 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline BL: Total	100.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline Most extr post-BL:tot Non/absent	36.6 Percentage of participants	26.0 Percentage of participants	37.4 Percentage of participants	26.8 Percentage of participants	47.2 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline Most extr. post-BL: total Mod.	20.3 Percentage of participants	22.8 Percentage of participants	20.3 Percentage of participants	24.4 Percentage of participants	13.0 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline Most extr post-BL:tot. Very severe	2.4 Percentage of participants	13.0 Percentage of participants	5.7 Percentage of participants	8.1 Percentage of participants	2.4 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline BL: Moderate	18.7 Percentage of participants	26.0 Percentage of participants	18.7 Percentage of participants	26.0 Percentage of participants	10.6 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline Baseline (BL): Non/absent	41.5 Percentage of participants	36.6 Percentage of participants	43.1 Percentage of participants	33.3 Percentage of participants	54.5 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline BL: Severe	7 Percentage of participants	13.8 Percentage of participants	8.9 Percentage of participants	16.3 Percentage of participants	8.9 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline BL: Very severe	5.7 Percentage of participants	4.9 Percentage of participants	4.1 Percentage of participants	3.3 Percentage of participants	0.8 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline Most extr. post-BL: total Mild	30.9 Percentage of participants	22.8 Percentage of participants	29.3 Percentage of participants	26.0 Percentage of participants	27.6 Percentage of participants	—
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline Most extr. post-BL: total Severe	9.8 Percentage of participants	15.4 Percentage of participants	7.3 Percentage of participants	14.6 Percentage of participants	9.8 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24 & 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study

Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=123 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Change From Baseline in EQ-5D-5L Index Scores Week 12	0.0 scores on a scale Standard Deviation 0.15	—	—	—	—	—
Core Phase: Change From Baseline in EQ-5D-5L Index Scores Week 24	0.0 scores on a scale Standard Deviation 0.15	—	—	—	—	—
Core Phase: Change From Baseline in EQ-5D-5L Index Scores Week 36	0.0 scores on a scale Standard Deviation 0.15	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24 & 36

Population: FAS comprised all patients who had signed informed consent and had been treated with at least one dose of study medication (pasireotide LAR) after enrollment into the study

Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine.

Outcome measures

Outcome measures
Measure	Lanreotide 120 mg n=123 Participants Participants were treated with lanreotide 120mg and assigned to Group 2 (before starting on Pasireotide in the Core phase).	Octreotide 30 mg Participants were treated with octreotide 30 mg and assigned to Group 2 (before starting on Pasireotide in the Core phase). .	Octreotide 40 mg Participants were treated with octreotide 40 mg and assigned to either Group 1 (if 40mg octreotide was approved in the country) or Group 2 if 40mg octreotide was not approved in the country (before starting on Pasireotide in the Core phase).	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.	Pasireotide With Concomitant Medication Participants received pasireotide along with other concomitant medications.or octreotide 40 mg.	Pasireotide LAR Overall This is the sum total of participants in under the previous treatments: lanreotide 120 mg, octreotide 30 mg or octreotide 40 mg.
Core Phase: Change From Baseline in EQ-5D-5L VAS Assessment Week 12	4.1 scores on a scale Standard Deviation 14.91	—	—	—	—	—
Core Phase: Change From Baseline in EQ-5D-5L VAS Assessment Week 24	3.4 scores on a scale Standard Deviation 13.49	—	—	—	—	—
Core Phase: Change From Baseline in EQ-5D-5L VAS Assessment Week 36	4.9 scores on a scale Standard Deviation 15.24	—	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 48, 60 & 72

Population: Extension Full Analysis Set (Extension FAS) included all the patients who received at least one dose of pasireotide LAR in the extension phase.

Percentage of patients achieving IGF-1 \<ULN at weeks 48, 60 \& 72 for participants with up-titrated to Pasireotide LAR 60 mg mg