Trial Outcomes & Findings for Efficacy and Safety of Pasireotide LAR (Long-acting Release) in Japanese Patients With Acromegaly or Pituitary Gigantism (NCT NCT01673646)

Last Updated: 2019-09-16

Results Overview

Percentage of participants with a reduction of mean growth hormone (GH) levels to \< 2.5 µg/L and the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits (age and sex related) at 3 months across all doses

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

Month 3

Results posted on

2019-09-16

Participant Flow

30 patients were planned and 33 patients were enrolled. The full analysis sets (FAS) consisted of 33 patients (11 patients per dose group).

Participant milestones

Participant milestones
Measure	Pasireotide LAR 20mg Enrolled patients were randomized to 20mg pasireotide LAR.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Overall Study STARTED	11	11	11
Overall Study Entered/Treated in Core Phase	11	11	11
Overall Study Completed Core Phase	9	10	10
Overall Study Entered Ext. Phase	7	9	9
Overall Study Did Not Enter Ext. Phase	2	1	1
Overall Study Treated Beyond 24 Months	7	8	8
Overall Study Discontinued Beyond 24 Months	0	4	1
Overall Study COMPLETED	7	4	7
Overall Study NOT COMPLETED	4	7	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Pasireotide LAR 20mg Enrolled patients were randomized to 20mg pasireotide LAR.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Overall Study Adverse Event	2	1	1
Overall Study Unsatisfactory therapeutic effect	0	2	0
Overall Study Condition no longer requires study drug	0	1	0
Overall Study Withdrawal by Subject	0	2	2
Overall Study Completed Core/did not enter Ext.	2	1	1

Baseline Characteristics

Full analysis set comprises all patients to whom study treatment had been assigned by randomization.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pasireotide LAR 20mg n=11 Participants Enrolled patients were randomized to 20mg pasireotide LAR.	Pasireotide LAR 40mg n=11 Participants Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg n=11 Participants Enrolled patients were randomized to 60mg pasireotide LAR.	Total n=33 Participants Total of all reporting groups
Age, Continuous	57.2 Years STANDARD_DEVIATION 11.48 • n=5 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	49.1 Years STANDARD_DEVIATION 13.75 • n=7 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	46.6 Years STANDARD_DEVIATION 14.60 • n=5 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	51.0 Years STANDARD_DEVIATION 13.71 • n=4 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.
Sex: Female, Male Female	4 Participants n=5 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	7 Participants n=7 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	2 Participants n=5 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	13 Participants n=4 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.
Sex: Female, Male Male	7 Participants n=5 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	4 Participants n=7 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	9 Participants n=5 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	20 Participants n=4 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.
Race/Ethnicity, Customized Asian	11 Participants n=5 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	11 Participants n=7 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	11 Participants n=5 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.	33 Participants n=4 Participants • Full analysis set comprises all patients to whom study treatment had been assigned by randomization.

PRIMARY outcome

Timeframe: Month 3

Population: The Full analysis Set (FAS): Comprises all patients to whom study treatment has been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the study treatment they have been assigned to during the randomization procedure.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Total-group Response Rate at Month 3	18.2 Percentage of participants Interval 7.0 to 35.5	—	—

SECONDARY outcome

Timeframe: Month 3

Population: FAS: Comprises all patients to whom study treatment has been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the study treatment they have been assigned to during the randomization procedure.

Percentage of participants with a reduction of mean GH levels to \< 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) at 3 months in each starting dose.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=11 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg n=11 Participants Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg n=11 Participants Enrolled patients were randomized to 60mg pasireotide LAR.
Response Rate at Month 3 by Randomized Dose Level	9.1 Percentage of participants Interval 0.2 to 41.3	36.4 Percentage of participants Interval 10.9 to 69.2	9.1 Percentage of participants Interval 0.2 to 41.3

SECONDARY outcome

Timeframe: Month 3

Percentage of participants with a reduction of mean GH levels to \< 2.5 µg/L at 3 months.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=11 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg n=11 Participants Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg n=11 Participants Enrolled patients were randomized to 60mg pasireotide LAR.
GH Response at Month 3 by Randomized Dose	27.3 Percentage of participants Interval 6.0 to 61.0	45.5 Percentage of participants Interval 16.7 to 76.6	18.2 Percentage of participants Interval 2.3 to 51.8

SECONDARY outcome

Timeframe: Month 3

Percentage of participants with the normalization of IGF-1 to within normal limits (age and sex related) at 3 months.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=11 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg n=11 Participants Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg n=11 Participants Enrolled patients were randomized to 60mg pasireotide LAR.
IGF-1 Response at Month 3 by Randomized Dose	18.2 Percentage of participants Interval 2.3 to 51.8	45.5 Percentage of participants Interval 16.7 to 76.6	9.1 Percentage of participants Interval 0.2 to 41.3

SECONDARY outcome

Timeframe: Months 3, 6, 9 & 12

Percentage of participants with a reduction of mean GH levels to \< 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) at 3, 6, 9 and 12 months

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Total-group Response Rate (GH & IGF-1) Over Time (Core Phase) Month 3	18.2 Percentage of participants Interval 7.0 to 35.5	—	—
Total-group Response Rate (GH & IGF-1) Over Time (Core Phase) Month 6	21.2 Percentage of participants Interval 9.0 to 38.9	—	—
Total-group Response Rate (GH & IGF-1) Over Time (Core Phase) Month 9	21.2 Percentage of participants Interval 9.0 to 38.9	—	—
Total-group Response Rate (GH & IGF-1) Over Time (Core Phase) Month 12	15.2 Percentage of participants Interval 5.1 to 31.9	—	—

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12

This refers to the percentage of participants with a reduction of growth hormone (GH) response rates to \<2.5 ug/L over time.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Percentage of Overall Participants With the Reduction of GH Levels to <2.5 ug/L by Visit (Core Phase) Month 3	30.3 Percenage of participants Interval 15.6 to 48.7	—	—
Percentage of Overall Participants With the Reduction of GH Levels to <2.5 ug/L by Visit (Core Phase) Month 6	33.3 Percenage of participants Interval 18.0 to 51.8	—	—
Percentage of Overall Participants With the Reduction of GH Levels to <2.5 ug/L by Visit (Core Phase) Month 9	30.3 Percenage of participants Interval 15.6 to 48.7	—	—
Percentage of Overall Participants With the Reduction of GH Levels to <2.5 ug/L by Visit (Core Phase) Month 12	36.4 Percenage of participants Interval 20.4 to 54.9	—	—

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12

This refers to the percentage of participants with the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits by visit.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Core Phase) Month 3	24.2 Percentage of participants Interval 11.1 to 42.3	—	—
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Core Phase) Month 6	33.3 Percentage of participants Interval 18.0 to 51.8	—	—
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Core Phase) Month 9	39.4 Percentage of participants Interval 22.9 to 57.9	—	—
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Core Phase) Month 12	27.3 Percentage of participants Interval 13.3 to 45.5	—	—

SECONDARY outcome

Timeframe: Ctrough: Day 28 after each injection 1-3, Cmax: 3 months after injections 1 and 3

Population: The pharmacokinetic (PK) analysis set (PAS) consists of full analysis set (FAS) who have evaluable PK concentration data.

Ctrough: The trough level concentration on day 28, 3 months post 1st, 2nd and 3rd injections of Pasireotide LAR. Cmax: The maximum concentration 3 months post the 1st injection and 3rd injection of LAR.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=11 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg n=11 Participants Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg n=11 Participants Enrolled patients were randomized to 60mg pasireotide LAR.
Summary of Pasireotide LAR PK Parameters of Ctrough & Cmax by Randomized Dose Level Ctrough Day 28, 1st inj	5.36 ng/mL Standard Deviation 3.35	8.41 ng/mL Standard Deviation 5.26	10.8 ng/mL Standard Deviation 5.12
Summary of Pasireotide LAR PK Parameters of Ctrough & Cmax by Randomized Dose Level Ctrough Day 28, 2nd inj	5.86 ng/mL Standard Deviation 2.38	10.7 ng/mL Standard Deviation 4.14	15.0 ng/mL Standard Deviation 9.12
Summary of Pasireotide LAR PK Parameters of Ctrough & Cmax by Randomized Dose Level Ctrough Day 28, 3rd inj	5.85 ng/mL Standard Deviation 2.28	12.2 ng/mL Standard Deviation 6.75	11.1 ng/mL Standard Deviation 4.99
Summary of Pasireotide LAR PK Parameters of Ctrough & Cmax by Randomized Dose Level Cmax, 1st inj	7.19 ng/mL Standard Deviation 3.48	10.3 ng/mL Standard Deviation 7.25	17.0 ng/mL Standard Deviation 13.7
Summary of Pasireotide LAR PK Parameters of Ctrough & Cmax by Randomized Dose Level Cmax, 3rd inj	8.23 ng/mL Standard Deviation 2.35	17.3 ng/mL Standard Deviation 9.61	16.2 ng/mL Standard Deviation 7.12

SECONDARY outcome

Timeframe: Day 28 after injections 1 and 3

Population: PAS: Consists of full analysis set (FAS) who have evaluable PK concentration data

The accumulation ratio was calculated as a ratio of (Ctrough day28, 3rd injection/Ctrough day28, 1st injection).

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=11 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg n=11 Participants Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg n=11 Participants Enrolled patients were randomized to 60mg pasireotide LAR.
Summary of Pasireotide LAR PK Parameter of Accumulation Ratio Randomized Dose Level	1.33 ratio Standard Deviation 0.530	1.85 ratio Standard Deviation 1.17	1.64 ratio Standard Deviation 1.41

SECONDARY outcome

Timeframe: Baseline, Months 6 , 12

Population: FAS: Comprises all patients to whom study treatment has been assigned by randomization. Protocol allowed to change treatment dose (eg, 20mg -\> 40mg -\>20mg -\> 40mg -\>60mg) based on efficacy and safety after 3month treatment. So we combined Arms/groups.

This shows the change in tumor volume from baseline to month 6 and from baseline to month 12 in patients treated with pasireotide LAR.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Change of Tumor Volume From Baseline Change from baseline @ Month 6	-21.0 mm^3 Interval -6532.0 to 1002.0	—	—
Change of Tumor Volume From Baseline Change from baseline @ Month 12	-1.00 mm^3 Interval -4084.0 to 1085.0	—	—

SECONDARY outcome

Timeframe: Baseline, Months 2.75, 3, 6, 9, 12, 18, 24

This shows the change in mean GH levels from baseline in median GH levels by visit.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Change in Mean GH Levels From Baseline Change from baseline @ Month 12	-8.90 ug/L Interval -159.2 to 3.0	—	—
Change in Mean GH Levels From Baseline Change from baseline @ Month 2.75	-7.60 ug/L Interval -157.2 to 39.3	—	—
Change in Mean GH Levels From Baseline Change from baseline @ Month 3	-5.98 ug/L Interval -99.2 to 39.3	—	—
Change in Mean GH Levels From Baseline Change from baseline @ Month 6	-7.27 ug/L Interval -149.8 to 39.3	—	—
Change in Mean GH Levels From Baseline Change from baseline @ Month 9	-8.83 ug/L Interval -163.8 to 39.3	—	—
Change in Mean GH Levels From Baseline Change from baseline @ Month 18	-15.68 ug/L Interval -23.9 to 39.3	—	—
Change in Mean GH Levels From Baseline Change from baseline @ Month 24	-16.67 ug/L Interval -25.5 to -1.4	—	—

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12

Change of clinical signs from baseline: ring size. In Japan, ring sizes are specified using a numerical scale, that only has whole sizes, and does not have simple linear correlation with diameter or circumference. Only numbers are used ranging from 1 to 27. For instance, a ring size of 1 in Japan is equivalent to an inside circumference ring size of 38.86 mm and a ring size of 27 in Japan is equivalent to an inside circumference ring size of 70.15 mm.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Change in Ring Size From Baseline Month 3	-1.00 other - Japanese ring size number Interval -3.0 to 0.0	—	—
Change in Ring Size From Baseline Month 6	-2.00 other - Japanese ring size number Interval -6.0 to 2.0	—	—
Change in Ring Size From Baseline Month 9	-2.00 other - Japanese ring size number Interval -6.0 to 1.0	—	—
Change in Ring Size From Baseline Month 12	-2.00 other - Japanese ring size number Interval -6.0 to 1.0	—	—

SECONDARY outcome

Timeframe: 12 Months (Core phase)

Population: Full analysis set (FAS) comprises all patients to whom study treatment has been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the study treatment they have been assigned to during the randomization procedure.

Number of participants with a change of clinical signs from baseline (BL): headache (HA), fatigue (FA), perspiration (PE), paresthesias (PA), osteoarthralgia (OS)

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=11 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg n=11 Participants Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg n=11 Participants Enrolled patients were randomized to 60mg pasireotide LAR.
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ BL: non/absent	9 Participants	6 Participants	10 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ most extreme post-BL: total severe	0 Participants	1 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ most extreme post-BL: total very severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ most extreme post-BL: total (all categories)	11 Participants	11 Participants	11 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ BL: non/absent	7 Participants	5 Participants	6 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ BL: mild	3 Participants	3 Participants	2 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ BL: moderate	1 Participants	2 Participants	3 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ BL: severe	0 Participants	1 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ BL: mild	1 Participants	4 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ BL: moderate	1 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ BL: severe	0 Participants	0 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ BL: very severe	0 Participants	1 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ BL: total (all categories)	11 Participants	11 Participants	11 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ most extreme post-BL: total non/absent	8 Participants	8 Participants	7 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ most extreme post-BL: total mild	3 Participants	2 Participants	3 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) HA @ most extreme post-BL: total moderate	0 Participants	0 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ BL: very severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ BL: total (all categories)	11 Participants	11 Participants	11 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ most extreme post-BL: total non/absent	4 Participants	3 Participants	5 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ most extreme post-BL: total mild	4 Participants	5 Participants	4 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ most extreme post-BL: total moderate	3 Participants	3 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ most extreme post-BL: total severe	0 Participants	0 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ most extreme post-BL: total very severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) FA @ most extreme post-BL: total (all categories)	11 Participants	11 Participants	11 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ BL: non/absent	6 Participants	6 Participants	3 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ BL: mild	5 Participants	3 Participants	6 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ BL: moderate	0 Participants	2 Participants	2 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ BL: severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ BL: very severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ BL: total (all categories)	11 Participants	11 Participants	11 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ most extreme post-BL: total non/absent	5 Participants	7 Participants	7 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ most extreme post-BL: total mild	5 Participants	2 Participants	3 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ most extreme post-BL: total moderate	1 Participants	1 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ most extreme post-BL: total severe	0 Participants	1 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ most extreme post-BL: total very severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PE @ most extreme post-BL: total (all categories)	11 Participants	11 Participants	11 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ BL: non/absent	9 Participants	5 Participants	7 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ BL: mild	1 Participants	1 Participants	3 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ BL: moderate	1 Participants	2 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ BL: severe	0 Participants	2 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ BL: very severe	0 Participants	1 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ BL: total (all categories)	11 Participants	11 Participants	11 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ most extreme post-BL: total non/absent	8 Participants	5 Participants	6 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ most extreme post-BL: total mild	1 Participants	2 Participants	3 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ most extreme post-BL: total moderate	2 Participants	2 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ most extreme post-BL: total severe	0 Participants	1 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ most extreme post-BL: total very severe	0 Participants	1 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) OS @ most extreme post-BL: total (all categories)	11 Participants	11 Participants	11 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ BL: non/absent	9 Participants	11 Participants	9 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ BL: mild	2 Participants	0 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ BL: moderate	0 Participants	0 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ BL: severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ BL: very severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ BL: total (all categories)	11 Participants	11 Participants	11 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ most extreme post-BL: total non/absent	7 Participants	9 Participants	9 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ most extreme post-BL: total mild	4 Participants	1 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ most extreme post-BL: total moderate	0 Participants	1 Participants	1 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ most extreme post-BL: total severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ most extreme post-BL: total very severe	0 Participants	0 Participants	0 Participants
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase) PA @ most extreme post-BL: total (all categories)	11 Participants	11 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12

Change in prolactin levels from baseline

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Change From Baseline in Prolactin Month 3	-43.00 pmol/L Interval -609.0 to 1087.0	—	—
Change From Baseline in Prolactin Month 6	0.00 pmol/L Interval -435.0 to 217.0	—	—
Change From Baseline in Prolactin Month 9	0.00 pmol/L Interval -479.0 to 913.0	—	—
Change From Baseline in Prolactin Month 12	0.00 pmol/L Interval -653.0 to 217.0	—	—

SECONDARY outcome

Timeframe: Months 18, 24

Population: FAS: Comprises all patients to whom study treatment has been assigned by randomization. The protocol allowed frequent dose changes even extension phase. In this case, separate data is not meaningful.

Percentage of participants with a reduction of mean GH levels to \< 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) a18 and 24 months of study treatment.

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Total-group Response Rate by Visit (Extension Phase) Month 18	12.5 Percentage of participants Interval 2.7 to 32.4	—	—
Total-group Response Rate by Visit (Extension Phase) Month 24	30.4 Percentage of participants Interval 13.2 to 52.9	—	—

SECONDARY outcome

Timeframe: Months 18, 24

Percentage of participants with a reduction of mean GH levels to \< 2.5µg/L at 18 and 24 months of study treatment

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Percentage of Overall Participants With the Reduction of Mean GH Levels to <2.5 ug/L by Visit (Extension Phase) Month 18	41.7 Percentage of participants Interval 22.1 to 63.4	—	—
Percentage of Overall Participants With the Reduction of Mean GH Levels to <2.5 ug/L by Visit (Extension Phase) Month 24	60.9 Percentage of participants Interval 38.5 to 80.3	—	—

SECONDARY outcome

Timeframe: Months 18, 24

Percentage of participants with the normalization of IGF-1 to within normal limits (age and sex related) at 18 and 24 months of study. treatment

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=33 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Extension Phase) Month 18	16.7 Percentage of participants Interval 4.7 to 37.4	—	—
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Extension Phase) Month 24	30.4 Percentage of participants Interval 13.2 to 52.9	—	—

SECONDARY outcome

Timeframe: Baselnine, Months 2.75, 3, 6, 9, 12, 18, 24

This shows a change of mean GH levels and somatostatin analogues (SSAs) from baseline in extension phase

Outcome measures

Outcome measures
Measure	Pasireotide LAR - All Participants n=20 Participants All patients randomized regardless of pasireotide LAR dose.	Pasireotide LAR 40mg n=13 Participants Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg Enrolled patients were randomized to 60mg pasireotide LAR.
Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase) Month 2.75	-8.84 ug/L Interval -25.6 to 39.3	-6.62 ug/L Interval -157.2 to -1.4	—
Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase) Month 3	-6.71 ug/L Interval -22.2 to 39.3	-5.04 ug/L Interval -99.2 to -1.4	—
Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase) Month 6	-8.15 ug/L Interval -25.4 to 39.3	-6.35 ug/L Interval -149.8 to -1.4	—
Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase) Month 9	-9.02 ug/L Interval -24.6 to 39.3	-8.72 ug/L Interval -163.8 to 1.8	—
Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase) Month 12	-10.10 ug/L Interval -29.1 to 3.0	-7.29 ug/L Interval -159.2 to -1.4	—
Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase) Month 18	-8.88 ug/L Interval -23.9 to 39.3	-7.70 ug/L Interval -155.7 to -0.3	—
Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase) Month 24	-9.76 ug/L Interval -25.5 to 39.3	-6.80 ug/L Interval -32.8 to -1.4	—

Adverse Events

Pasireotide LAR 20mg

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Pasireotide LAR 40mg

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Pasireotide LAR 60mg

Serious events: 5 serious events

Other events: 11 other events

Deaths: 0 deaths

Pasireotide LAR - All Participants (All Patieents)

Serious events: 11 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pasireotide LAR 20mg n=11 participants at risk Enrolled patients were randomized to 20mg pasireotide LAR.	Pasireotide LAR 40mg n=11 participants at risk Enrolled patients were randomized to 40mg pasireotide LAR.	Pasireotide LAR 60mg n=11 participants at risk Enrolled patients were randomized to 60mg pasireotide LAR.	Pasireotide LAR - All Participants (All Patieents) n=33 participants at risk Patients who were randomized to the study - regardless of whether they were in the Core or Extension phase.
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	3.0% 1/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Gastrointestinal disorders Inguinal hernia	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	6.1% 2/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Gastrointestinal disorders Large intestine polyp	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	6.1% 2/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Hepatobiliary disorders Bile duct stone	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	3.0% 1/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Infections and infestations Influenza	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	3.0% 1/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Infections and infestations Meningitis bacterial	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	3.0% 1/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	3.0% 1/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Metabolism and nutrition disorders Hyperglycaemia	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	6.1% 2/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	3.0% 1/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Psychiatric disorders Persistent depressive disorder	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	3.0% 1/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	9.1% 1/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	0.00% 0/11 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.	3.0% 1/33 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 1513 days. Protocol allowed dose modification after month 3 and so analyzing AE separately was did not provide a clinically meaningful data.

Other adverse events

Additional Information

Clinical Disclosure Office

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