Trial Outcomes & Findings for Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly (NCT NCT02685709)

Last Updated: 2022-04-22

Results Overview

Proportion of patients who are biochemically controlled throughout the RCT phase. A patient was considered biochemically controlled if IGF-1 Time Weighted Average (TWA) during the RCT phase is \<1.3 ULN

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

146 participants

Primary outcome timeframe

62 weeks

Results posted on

2022-04-22

Participant Flow

146 patients were enrolled into the Run-in phase. A total of 116 patients completed the Run-in phase and 30 patients discontinued the Run in phase. Of the 116 patients who completed the Run-in phase, 92 patients with IGF-1\<1.3 ULN entered the RCT phase, 11 patients with IGF-1≥1.3 and \<2 ULN on the highest octreotide dose entered the Combination phase, and 13 patients did not continue treatment.

Prior to Run-in - all patients treated with SRLs (59.6% octreotide and 39.4% on lanreotide). 78.8% of patients were treated with medium to high doses of SRLs. Prior to RCT - all patients were on oral octreotide capsules.

Participant milestones

Participant milestones
Measure	Run-in Phase Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day determined by individual dose titration	RCT Phase - Oral Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide- 10, 20, 30, 40 mg. Lanreotide- 60, 90, 120mg.	Combination Phase (Sub-study) Octreotide capsules plus cabergoline Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day Cabergoline: Cabergoline - Up to 3.5mg/week
Run-in Phase STARTED	146	0	0	0
Run-in Phase COMPLETED	116	0	0	0
Run-in Phase NOT COMPLETED	30	0	0	0
RCT Phase STARTED	0	55	37	0
RCT Phase COMPLETED	0	54	35	0
RCT Phase NOT COMPLETED	0	1	2	0
Combination Phase STARTED	0	0	0	14
Combination Phase COMPLETED	0	0	0	8
Combination Phase NOT COMPLETED	0	0	0	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Number of participants was breakdown per study phase.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Run-in Phase n=146 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=37 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.	Combination Phase (Sub-study) n=14 Participants Octreotide capsules plus cabergoline Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day Cabergoline: Cabergoline - 3.5mg/week	Total n=252 Participants Total of all reporting groups
Age, Categorical Run-in phase · <=18 years	0 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=146 Participants • Number of participants was breakdown per study phase.
Age, Categorical Run-in phase · Between 18 and 65 years	124 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	124 Participants n=146 Participants • Number of participants was breakdown per study phase.
Age, Categorical Run-in phase · >=65 years	22 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	22 Participants n=146 Participants • Number of participants was breakdown per study phase.
Age, Categorical RCT phase · <=18 years	0 Participants Number of participants was breakdown per study phase.	0 Participants n=55 Participants • Number of participants was breakdown per study phase.	0 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=92 Participants • Number of participants was breakdown per study phase.
Age, Categorical RCT phase · Between 18 and 65 years	0 Participants Number of participants was breakdown per study phase.	46 Participants n=55 Participants • Number of participants was breakdown per study phase.	32 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	78 Participants n=92 Participants • Number of participants was breakdown per study phase.
Age, Categorical RCT phase · >=65 years	0 Participants Number of participants was breakdown per study phase.	9 Participants n=55 Participants • Number of participants was breakdown per study phase.	5 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	14 Participants n=92 Participants • Number of participants was breakdown per study phase.
Age, Categorical Combination Phase · <=18 years	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.
Age, Categorical Combination Phase · Between 18 and 65 years	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	11 Participants n=14 Participants • Number of participants was breakdown per study phase.	11 Participants n=14 Participants • Number of participants was breakdown per study phase.
Age, Categorical Combination Phase · >=65 years	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	3 Participants n=14 Participants • Number of participants was breakdown per study phase.	3 Participants n=14 Participants • Number of participants was breakdown per study phase.
Age, Continuous Run-in phase	54.1 years STANDARD_DEVIATION 10.5 • n=146 Participants • Number of participants was breakdown per study phase.	—	—	—	54.1 years STANDARD_DEVIATION 10.5 • n=146 Participants • Number of participants was breakdown per study phase.
Age, Continuous RCT phase	—	54.1 years STANDARD_DEVIATION 10.88 • n=55 Participants • Number of participants was breakdown per study phase.	55.2 years STANDARD_DEVIATION 8.78 • n=37 Participants • Number of participants was breakdown per study phase.	—	54.5 years STANDARD_DEVIATION 10.05 • n=92 Participants • Number of participants was breakdown per study phase.
Age, Continuous Combination phase	—	—	—	59.8 years STANDARD_DEVIATION 5.82 • n=14 Participants • Number of participants was breakdown per study phase.	59.8 years STANDARD_DEVIATION 5.82 • n=14 Participants • Number of participants was breakdown per study phase.
Sex: Female, Male Run-in phase · Female	94 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	94 Participants n=146 Participants • Number of participants was breakdown per study phase.
Sex: Female, Male Run-in phase · Male	52 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	52 Participants n=146 Participants • Number of participants was breakdown per study phase.
Sex: Female, Male RCT phase · Female	0 Participants Number of participants was breakdown per study phase.	35 Participants n=55 Participants • Number of participants was breakdown per study phase.	26 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	61 Participants n=92 Participants • Number of participants was breakdown per study phase.
Sex: Female, Male RCT phase · Male	0 Participants Number of participants was breakdown per study phase.	20 Participants n=55 Participants • Number of participants was breakdown per study phase.	11 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	31 Participants n=92 Participants • Number of participants was breakdown per study phase.
Sex: Female, Male Combination phase · Female	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	10 Participants n=14 Participants • Number of participants was breakdown per study phase.	10 Participants n=14 Participants • Number of participants was breakdown per study phase.
Sex: Female, Male Combination phase · Male	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	4 Participants n=14 Participants • Number of participants was breakdown per study phase.	4 Participants n=14 Participants • Number of participants was breakdown per study phase.
Ethnicity (NIH/OMB) Run-in phase · Hispanic or Latino	5 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	5 Participants n=146 Participants • Number of participants was breakdown per study phase.
Ethnicity (NIH/OMB) Run-in phase · Not Hispanic or Latino	130 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	130 Participants n=146 Participants • Number of participants was breakdown per study phase.
Ethnicity (NIH/OMB) Run-in phase · Unknown or Not Reported	11 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	11 Participants n=146 Participants • Number of participants was breakdown per study phase.
Ethnicity (NIH/OMB) RCT phase · Hispanic or Latino	0 Participants Number of participants was breakdown per study phase.	1 Participants n=55 Participants • Number of participants was breakdown per study phase.	2 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	3 Participants n=92 Participants • Number of participants was breakdown per study phase.
Ethnicity (NIH/OMB) RCT phase · Not Hispanic or Latino	0 Participants Number of participants was breakdown per study phase.	50 Participants n=55 Participants • Number of participants was breakdown per study phase.	33 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	83 Participants n=92 Participants • Number of participants was breakdown per study phase.
Ethnicity (NIH/OMB) RCT phase · Unknown or Not Reported	0 Participants Number of participants was breakdown per study phase.	4 Participants n=55 Participants • Number of participants was breakdown per study phase.	2 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	6 Participants n=92 Participants • Number of participants was breakdown per study phase.
Ethnicity (NIH/OMB) Combination phase · Hispanic or Latino	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.
Ethnicity (NIH/OMB) Combination phase · Not Hispanic or Latino	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	14 Participants n=14 Participants • Number of participants was breakdown per study phase.	14 Participants n=14 Participants • Number of participants was breakdown per study phase.
Ethnicity (NIH/OMB) Combination phase · Unknown or Not Reported	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Run-in phase · American Indian or Alaska Native	0 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=146 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Run-in phase · Asian	1 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	1 Participants n=146 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Run-in phase · Native Hawaiian or Other Pacific Islander	0 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=146 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Run-in phase · Black or African American	3 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	3 Participants n=146 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Run-in phase · White	133 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	133 Participants n=146 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Run-in phase · More than one race	9 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	9 Participants n=146 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Run-in phase · Unknown or Not Reported	0 Participants n=146 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=146 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) RCT phase · American Indian or Alaska Native	0 Participants Number of participants was breakdown per study phase.	0 Participants n=55 Participants • Number of participants was breakdown per study phase.	0 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=92 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) RCT phase · Asian	0 Participants Number of participants was breakdown per study phase.	0 Participants n=55 Participants • Number of participants was breakdown per study phase.	0 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=92 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) RCT phase · Native Hawaiian or Other Pacific Islander	0 Participants Number of participants was breakdown per study phase.	0 Participants n=55 Participants • Number of participants was breakdown per study phase.	0 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=92 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) RCT phase · Black or African American	0 Participants Number of participants was breakdown per study phase.	2 Participants n=55 Participants • Number of participants was breakdown per study phase.	0 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	2 Participants n=92 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) RCT phase · White	0 Participants Number of participants was breakdown per study phase.	49 Participants n=55 Participants • Number of participants was breakdown per study phase.	35 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	84 Participants n=92 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) RCT phase · More than one race	0 Participants Number of participants was breakdown per study phase.	4 Participants n=55 Participants • Number of participants was breakdown per study phase.	2 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	6 Participants n=92 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) RCT phase · Unknown or Not Reported	0 Participants Number of participants was breakdown per study phase.	0 Participants n=55 Participants • Number of participants was breakdown per study phase.	0 Participants n=37 Participants • Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=92 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Combination phase · American Indian or Alaska Native	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Combination phase · Asian	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Combination phase · Native Hawaiian or Other Pacific Islander	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Combination phase · Black or African American	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Combination phase · White	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	14 Participants n=14 Participants • Number of participants was breakdown per study phase.	14 Participants n=14 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Combination phase · More than one race	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.
Race (NIH/OMB) Combination phase · Unknown or Not Reported	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.	0 Participants n=14 Participants • Number of participants was breakdown per study phase.
Region of Enrollment Hungary	3 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	1 Participants n=55 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	1 Participants n=37 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	—	2 Participants n=92 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .
Region of Enrollment United States	37 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	14 Participants n=55 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	10 Participants n=37 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	3 Participants n=14 Participants • Region of enrollment was only captured for the Combination phase sub-study, in which 14 patients were included. .	3 Participants n=14 Participants • Region of enrollment was only captured for the Combination phase sub-study, in which 14 patients were included. .
Region of Enrollment Spain	6 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	1 Participants n=55 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	3 Participants n=37 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	—	4 Participants n=92 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .
Region of Enrollment Russia	65 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	24 Participants n=55 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	18 Participants n=37 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	10 Participants n=14 Participants • Region of enrollment was only captured for the Combination phase sub-study, in which 14 patients were included. .	10 Participants n=14 Participants • Region of enrollment was only captured for the Combination phase sub-study, in which 14 patients were included. .
Region of Enrollment Austria	6 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	5 Participants n=55 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	0 Participants n=37 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	—	5 Participants n=92 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .
Region of Enrollment Italy	2 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	1 Participants n=55 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	0 Participants n=37 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	—	1 Participants n=92 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .
Region of Enrollment France	10 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	4 Participants n=55 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	2 Participants n=37 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	—	6 Participants n=92 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .
Region of Enrollment Lithuania	8 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	1 Participants n=55 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	1 Participants n=37 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	—	2 Participants n=92 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .
Region of Enrollment Serbia	8 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	4 Participants n=55 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	2 Participants n=37 Participants • Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) .	1 Participants n=14 Participants • Region of enrollment was only captured for the Combination phase sub-study, in which 14 patients were included. .	1 Participants n=14 Participants • Region of enrollment was only captured for the Combination phase sub-study, in which 14 patients were included. .
Region of Enrollment Germany	1 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.	—	—	—	1 Participants n=146 Participants • Region of enrollment was summarized in the Run-in phase only, where 146 were randomized.
IGF-1 levels Run-in phase	0.9 X Upper limit of normal (ULN) STANDARD_DEVIATION 0.27 • n=146 Participants • Mean calculated is phase-specific.	—	—	—	0.9 X Upper limit of normal (ULN) STANDARD_DEVIATION 0.27 • n=146 Participants • Mean calculated is phase-specific.
IGF-1 levels RCT phase	—	0.9 X Upper limit of normal (ULN) STANDARD_DEVIATION 0.35 • n=55 Participants • Mean calculated is phase-specific.	0.8 X Upper limit of normal (ULN) STANDARD_DEVIATION 0.21 • n=37 Participants • Mean calculated is phase-specific.	—	0.9 X Upper limit of normal (ULN) STANDARD_DEVIATION 0.30 • n=92 Participants • Mean calculated is phase-specific.
IGF-1 levels Combination phase	—	—	—	1.5 X Upper limit of normal (ULN) STANDARD_DEVIATION 0.35 • n=14 Participants • Mean calculated is phase-specific.	1.5 X Upper limit of normal (ULN) STANDARD_DEVIATION 0.35 • n=14 Participants • Mean calculated is phase-specific.
IGF-I categorical Run-in phase- ≤ 1 ULN	98 Participants n=146 Participants • Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	98 Participants n=146 Participants • Number calculated is phase-specific.
IGF-I categorical Run-in phase- > 1 to < 1.3 ULN	38 Participants n=146 Participants • Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	38 Participants n=146 Participants • Number calculated is phase-specific.
IGF-I categorical Run-in phase- ≥ 1.3 ULN	10 Participants n=146 Participants • Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	10 Participants n=146 Participants • Number calculated is phase-specific.
IGF-I categorical RCT phase- ≤ 1 ULN	0 Participants Number calculated is phase-specific.	37 Participants n=55 Participants • Number calculated is phase-specific.	29 Participants n=37 Participants • Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	66 Participants n=92 Participants • Number calculated is phase-specific.
IGF-I categorical RCT phase- > 1 to < 1.3 ULN	0 Participants Number calculated is phase-specific.	12 Participants n=55 Participants • Number calculated is phase-specific.	8 Participants n=37 Participants • Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	20 Participants n=92 Participants • Number calculated is phase-specific.
IGF-I categorical RCT phase- ≥ 1.3 ULN	0 Participants Number calculated is phase-specific.	6 Participants n=55 Participants • Number calculated is phase-specific.	0 Participants n=37 Participants • Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	6 Participants n=92 Participants • Number calculated is phase-specific.
IGF-I categorical Combination phase- ≤ 1 ULN	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	1 Participants n=14 Participants • Number calculated is phase-specific.	1 Participants n=14 Participants • Number calculated is phase-specific.
IGF-I categorical Combination phase- > 1 to < 1.3 ULN	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	4 Participants n=14 Participants • Number calculated is phase-specific.	4 Participants n=14 Participants • Number calculated is phase-specific.
IGF-I categorical Combination phase- ≥ 1.3 ULN	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	0 Participants Number calculated is phase-specific.	9 Participants n=14 Participants • Number calculated is phase-specific.	9 Participants n=14 Participants • Number calculated is phase-specific.
GH Run-in phase	0.88 ng/ mL STANDARD_DEVIATION 0.818 • n=146 Participants • Data analyzed in study-specific.	—	—	—	0.88 ng/ mL STANDARD_DEVIATION 0.818 • n=146 Participants • Data analyzed in study-specific.
GH RCT phase	—	0.55 ng/ mL STANDARD_DEVIATION 0.544 • n=55 Participants • Data analyzed in study-specific.	0.62 ng/ mL STANDARD_DEVIATION 0.634 • n=37 Participants • Data analyzed in study-specific.	—	0.58 ng/ mL STANDARD_DEVIATION 0.579 • n=92 Participants • Data analyzed in study-specific.
GH Combination phase	—	—	—	0.94 ng/ mL STANDARD_DEVIATION 0.544 • n=14 Participants • Data analyzed in study-specific.	0.94 ng/ mL STANDARD_DEVIATION 0.544 • n=14 Participants • Data analyzed in study-specific.
Acromegaly Index of Severity (AIS) symptom score Run-in phase	4.8 units on a scale STANDARD_DEVIATION 3.1 • n=146 Participants • Analysis performed is phase-specific.	—	—	—	4.8 units on a scale STANDARD_DEVIATION 3.1 • n=146 Participants • Analysis performed is phase-specific.
Acromegaly Index of Severity (AIS) symptom score RCT phase	—	4.2 units on a scale STANDARD_DEVIATION 2.92 • n=55 Participants • Analysis performed is phase-specific.	5 units on a scale STANDARD_DEVIATION 2.98 • n=37 Participants • Analysis performed is phase-specific.	—	4.5 units on a scale STANDARD_DEVIATION 2.96 • n=92 Participants • Analysis performed is phase-specific.
Acromegaly Index of Severity (AIS) symptom score Combination phase	—	—	—	6.8 units on a scale STANDARD_DEVIATION 3.95 • n=14 Participants • Analysis performed is phase-specific.	6.8 units on a scale STANDARD_DEVIATION 3.95 • n=14 Participants • Analysis performed is phase-specific.

PRIMARY outcome

Timeframe: 62 weeks

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=37 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients Who Are Biochemically Controlled Throughout the RCT Phase	50 Participants	37 Participants

SECONDARY outcome

Timeframe: Week 62/ End of treatment; EOT

Proportion of patients with clinical and biochemical control at the end of the RCT phase. Patients were considered biochemically and clinically controlled if they met both of the following criteria: * Their IGF-1 TWA during the RCT phase was \<1.3 times ULN * Their AIS score at week 62/EOT was maintained or reduced compared to week 26 (start of RCT phase)

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=37 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients With Clinical and Biochemical Control at the End of the RCT Phase	36 Participants	27 Participants

SECONDARY outcome

Timeframe: 62 weeks

Proportion of patients who maintain or reduce the overall number of active acromegaly symptoms at the end of the RCT phase (week 62/ EOT) , compared to week 26 (start of the RCT phase

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=37 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients Who Maintain or Reduce the Overall Number of Active Acromegaly Symptoms at the End of the RCT Phase	41 Participants	26 Participants

SECONDARY outcome

Timeframe: 62 weeks

Proportion of patients who maintain or improve their overall Acromegaly index of severity (AIS) score at the end of the RCT phase (improvement defined as a reduction of at least one point in the AIS score), compared to week 26 (start of the RCT phase)

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=37 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients Who Maintain or Improve Their Overall Acromegaly Index of Severity (AIS) Score at the End of the RCT Phase	40 Participants	25 Participants

SECONDARY outcome

Timeframe: 62 weeks

Proportion of patients of those completing the RCT phase (at a time octreotide capsules were not commercially available at the specific country), who entered the Study Extension phase, overall and by treatment group

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=54 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=35 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients of Those Completing the RCT Phase Who Entered the Study Extension Phase	34 Participants	18 Participants

SECONDARY outcome

Timeframe: Change from Week 26 to week 62

Change in IGF-1 levels from the start of the randomized phase to the end of RCT phase. Complete Responder (CR) is defined as IGF-1 ≤ 1 x ULN; Partial Responder (PR) is defined as 1 x ULN \< IGF-1 \< 1.3 x ULN, and Non-Responder (NR): IGF-1 ≥ 1.3 x ULN

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=37 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Change in IGF-1 Levels in the RCT Phase	-0.01 x Upper limit of normal ("ULN") Standard Deviation 0.199	-0.04 x Upper limit of normal ("ULN") Standard Deviation 0.133

SECONDARY outcome

Timeframe: Change from Week 26 to week 62

Change in GH levels from the start of the randomized phase through the end of RCT phase.

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=37 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Change in GH Levels in the RCT Phase	-0.02 ng/mL Standard Deviation 0.506	0.27 ng/mL Standard Deviation 1.219

OTHER_PRE_SPECIFIED outcome

Timeframe: 62 weeks

Proportion of patients reporting injection site reactions (ISRs). Acromegaly treatment satisfaction questionnaire (ACRO-TSQ) is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive ACRO-TSQ change scores indicate improvement while negative change scores indicate worsening.

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=36 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients Reporting Injection Site Reactions in the Acro-TSQ During the RCT Phase	0 Participants	17 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 62 weeks

Proportion of patients reporting interference with daily activities in the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) during the RCT phase. Acro-TSQ is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive Acro-TSQ change scores indicate improvement while negative change scores indicate worsening.

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=16 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients Reporting Interference With Daily Activities in Acro-TSQ During the RCT Phase	0 Participants	13 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Average of weeks 58 and 62

Proportion of patients on octreotide capsules who are biochemically controlled at the end of the RCT phase defined as IGF-1\< 1.3 x ULN based on average of weeks 58 and 62

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=37 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Analysis	49 Participants	35 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 62 weeks

Proportion of patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark sensitivity analysis- Week 26 responders

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=48 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=36 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Week 26 Responders on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Sensitivity Analysis	45 Participants	34 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 weeks

Proportion of patients biochemically controlled at the end of the Run-in phase, defined as average IGF-1 levels during weeks 24 and 26 \< 1.3xULN

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=146 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients Biochemically Controlled at the End of Run-in	94 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 weeks

Proportion of patients with a reduction in the overall number of active acromegaly symptoms at the end of the Run-in phase compared to Baseline

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=146 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients With a Reduction in the Overall Number of Active Acromegaly Symptoms at the End of the Run-in Phase	97 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 weeks

Proportion of patients with improved AIS score at the end of the Run-in phase compared to Baseline Acromegaly index of severity (AIS) at the end of Run-in phase compared to Baseline. The Acromegaly Index of Severity (AIS) symptom score is calculated based on the presence and severity of 5 acromegaly signs/symptoms: headache, swelling of extremities, joint pain, sweating, and fatigue. Each symptom was graded from no symptoms (score 0), to mild symptoms (1), moderate (2), or severe symptoms (3).

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=92 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Proportion of Patients With Improved Acromegaly Index of Severity (AIS) Score at the End of the Run-in Phase	45 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 weeks

Population: All patients who were randomized to the RCT phase

Change from baselines in EQ-5D-5L Index scores in randomized participants during the Run-in phase. EQ-5D-5L (five severity levels EQ-5D) is a standardized instrument completed by the patient for use as a measure of health outcome applicable to a wide range of health conditions. It comprises 5 dimensions of health: mobility, ability to self care, ability to undertake usual activities, pain and discomfort, and anxiety and depression. Based on qualitative and quantitative studies conducted by the EuroQol Group, there are 5 levels under each domain: 'no problems' (assigned a value of 1), 'slight problems' (assigned a value of 2), 'moderate problems' (assigned a value of 3), 'severe problems' (assigned a value of 4), and 'unable to/extreme problems' (assigned a value of 5). An EQ-5D Index score is calculated based on the responses to these 5 dimensions of health. Weights for use in the index calculation are not universally available. Higher values represent better health states.

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=92 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Index Scores During the Run-in Phase	0.0433 units on a scale Interval 0.011 to 0.0755	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 weeks

Work Productivity and Activity Impairment Questionnaire- RCT phase. WPAI:SHP is a standardized and validated PRO questionnaire to measure health outcomes in clinical trial settings. It measures time missed from work, impairment of work and regular activities due to overall health and symptoms, relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity, and global measures of work and interference with regular activity. The WPAI yields 4 types of scores: (1) absenteeism (work time missed); (2) presenteeism (impairment at work/reduced on-the-job effectiveness); (3) work productivity loss (overall work impairment/absenteeism plus presenteeism); and (4) activity impairment. Each of the 4 WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes).

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=55 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables n=37 Participants Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Change From Baseline to End of RCT Phase in WPAI Absenteeism (%)	-0.34 Percentage change from Baseline RCT Interval -2.11 to 1.43	0.79 Percentage change from Baseline RCT Interval -1.53 to 3.12
Change From Baseline to End of RCT Phase in WPAI Presenteeism (%)	1.85 Percentage change from Baseline RCT Interval -4.48 to 8.17	5.98 Percentage change from Baseline RCT Interval -2.02 to 13.98
Change From Baseline to End of RCT Phase in WPAI Work productivity loss (%)	1.49 Percentage change from Baseline RCT Interval -5.09 to 8.08	6.93 Percentage change from Baseline RCT Interval -1.74 to 15.59
Change From Baseline to End of RCT Phase in WPAI Activity impairment (%)	0.84 Percentage change from Baseline RCT Interval -4.34 to 6.02	4.34 Percentage change from Baseline RCT Interval -2.1 to 10.77

OTHER_PRE_SPECIFIED outcome

Timeframe: 62 weeks

Work Productivity and Activity Impairment Questionnaire- Run-in phase. WPAI:SHP is a standardized and validated PRO questionnaire to measure health outcomes in clinical trial settings. It measures time missed from work, impairment of work and regular activities due to overall health and symptoms, relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity, and global measures of work and interference with regular activity. The WPAI yields 4 types of scores: (1) absenteeism (work time missed); (2) presenteeism (impairment at work/reduced on-the-job effectiveness); (3) work productivity loss (overall work impairment/absenteeism plus presenteeism); and (4) activity impairment. Each of the 4 WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes).

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=146 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Change From Baseline to End of Run-in Phase in WPAI Absenteeism (%)	-0.81 Percentage change from Run-in baseline Interval -3.84 to 2.21	—
Change From Baseline to End of Run-in Phase in WPAI Presenteeism (%)	-6.65 Percentage change from Run-in baseline Interval -12.39 to -0.9	—
Change From Baseline to End of Run-in Phase in WPAI Work Productivity Loss (%)	-6.92 Percentage change from Run-in baseline Interval -12.83 to -1.02	—
Change From Baseline to End of Run-in Phase in WPAI Activity Impairment (%)	-4.94 Percentage change from Run-in baseline Interval -9.17 to -0.71	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 weeks

Population: Change in Acro-TSQ domains in randomized patients

Change in Acromegaly treatment satisfaction questionnaire (ACRO-TSQ) PRO questionnaire from baseline to end of Run-in phase in randomized patients. Acro-TSQ is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive Acro-TSQ change scores indicate improvement while negative change scores indicate worsening.

Outcome measures

Outcome measures
Measure	RCT Phase - Oral n=57 Participants Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day	RCT Phase - Injectables Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg.
Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients. Treatment satisfaction - Change from baseline	6.73 score on a scale Interval 0.9 to 12.55	—
Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients. Emotional reaction - Change from baseline	9.65 score on a scale Interval 3.31 to 15.98	—
Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients. GI interference - Change from baseline	4.24 score on a scale Interval -1.32 to 9.8	—
Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients. Symptom interference- Change from baseline	2.45 score on a scale Interval -2.1 to 7.0	—
Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients. Treatment convenience - Change from baseline	6.37 score on a scale Interval 0.25 to 12.5	—

Adverse Events

Run-in Phase

Serious events: 6 serious events

Other events: 106 other events

Deaths: 0 deaths

RCT Phase - Oral

Serious events: 3 serious events

Other events: 39 other events

Deaths: 1 deaths

RCT Phase - Injectables

Serious events: 3 serious events

Other events: 26 other events

Deaths: 0 deaths

Combination Phase (Sub-study)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Run-in Phase n=146 participants at risk Oral octreotide capsules Octreotide capsules	RCT Phase - Oral n=55 participants at risk Oral octreotide capsules Octreotide capsules	RCT Phase - Injectables n=37 participants at risk Injectable somatostatin analogs (octreotide or lanreotide) Octreotide capsules	Combination Phase (Sub-study) n=14 participants at risk Octreotide capsules plus cabergoline Octreotide capsules
Cardiac disorders Atrial flutter	0.68% 1/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Cardiac disorders Cardiac failure	0.68% 1/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Cardiac disorders Cardiac failure congestive	0.68% 1/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Hepatobiliary disorders Cholecystitis acute	0.68% 1/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Hepatobiliary disorders Post cholecystectomy syndrome	0.68% 1/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Hepatobiliary disorders Pancreatitis acute	0.68% 1/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Cardiac disorders Acute myocardial infarction	0.00% 0/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	1.8% 1/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	2.7% 1/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Cardiac disorders Pericarditis	0.00% 0/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	1.8% 1/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Cardiac disorders Sinus bradycardia	0.00% 0/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	2.7% 1/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	2.7% 1/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/146 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	1.8% 1/55 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/37 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.	0.00% 0/14 • 1 year, 3 months for both the Run-in and RCT phases. Safety population: All participants enrolled in the study who received any amount of the study drug.

Other adverse events

Additional Information

Asi Haviv, VP Clinical development

Amryt

Phone: 972 8 9393888

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place