Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly

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

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)

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

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)

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

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

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

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.

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.

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

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

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

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

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).

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.

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).

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).

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.