An Extension Study to Assess the Long-Term Safety and Efficacy of Pasireotide in Participants With Acromegaly

A participant was a responder to a dose level if the mean GH level after dosing (t30, t60, t90, and t120) was below/equal to 2.5 microgram/litre (μg/L), and if the mean of IGF-1 of the two pre-dose values (t-30, t-1) was within normal limits for age-sex matched controls. If three or more of t30, t60, t90, or t120 were missing, mean GH was considered missing. If either t-30 or t-1 was missing, mean IGF-1 was considered missing. Pasireotide incident dose classes were defined by total daily doses ranges (\<1200 μg/d, 1200 to \<1500 μg/d, ≥ 1500 μg/d).

Time frame: Month 9 (Month 9 visit is at the completion of six months in this extension study)

Population: Efficacy analyzable population included all participants who received at least one dose of pasireotide during the extension study and had at least one post-extension baseline efficacy evaluation. Overall number of participants analyzed is the number of participants with at least 2 GH measurements and both predose IGF-1 measurements at the corresponding visit.

An AE was any undesirable sign, symptom or medical condition that occurred after starting study drug even if the event was not considered to be related to study drug. Percentage of participants with any AE were categorized by pasireotide incident dose classes, which were defined by total daily doses ranges (\<1200 μg/d, 1200 to \<1500 μg/d, ≥ 1500 μg/d).

Time frame: From start of study drug treatment up to end of study (approximately 111 months)

Population: Safety population included all participants who had received pasireotide s.c. in the extension study.

Sleep apnea symptoms were assessed using the Epworth Sleepiness Scale (ESS). The ESS is a self-administered questionnaire with 8 questions. It provides a measure of a person's general level of daytime sleepiness, or average sleep propensity in daily life. Percentage of participants were reported in 8 different situations: sitting and reading; watching TV; sitting, inactive in a public place; passenger in a car, an hour without break; lying down to rest in the afternoon; sitting and talking to someone; sitting quietly after a lunch without alcohol; and in a car, stopped a few minutes in the traffic. The participants were rated: 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, 3 = high chance of dozing. Higher scores indicate more severe daytime sleepiness.

Time frame: Core study baseline till the last assessment of the extension study (up to approximately 114 months)

Population: Efficacy analyzable population included all participants who received at least one dose of pasireotide during the extension study and had at least one post-extension baseline efficacy evaluation.

Participants scored the following symptoms of acromegaly: Headache, perspiration, paresthesia, fatigue, osteoarthralgia, and carpal tunnel syndrome on a 5-point scale (0 = None/absent, 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Very severe).

Time frame: Core study baseline till the last assessment of the extension study (up to approximately 114 months)

Population: Efficacy analyzable population included all participants who received at least one dose of pasireotide during the extension study and had at least one post-extension baseline efficacy evaluation.

Pituitary Tumor Volumes were assessed by MRI. Core study baseline was defined as the last non-missing observation prior to the start of Sandostatin s.c. treatment.

Time frame: Core study baseline, Months 9, 27, 63, 75 and 99

Population: Efficacy analyzable population included all participants who received at least one dose of pasireotide during the extension study and had at least one post-extension baseline efficacy evaluation. Number analyzed is the number of participants with data available at specified time points.

Time to tumor response was defined as time from Sandostatin baseline (core study baseline) to at least 20% decrease in tumor volume.

Time frame: Core study baseline to at least a 20% decrease in pituitary tumor volume (up to approximately 114 months)

Population: Efficacy analyzable population included all participants who received at least one dose of pasireotide during the extension study and had at least one post-extension baseline efficacy evaluation. Overall number of participants analyzed is the number of participants with data available at the specified time point.