Trial Outcomes & Findings for An Extension Study to Assess the Long-Term Safety and Efficacy of Pasireotide in Participants With Acromegaly (NCT NCT00171730)

Last Updated: 2021-09-05

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

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

Results posted on

2021-09-05

Participant Flow

This extension study was an open label, single arm, multi-center study in participants with acromegaly who had completed all four treatment regimens in the core study CSOM230B2201 (NCT00088582) and achieved biochemical control or had clinically relevant improvement according to Investigator judgement, from at least one of the pasireotide regimens.

Baseline visit in this extension study is referred as Month 3 which was the end of core study. Subsequent visits occurred at every 3 months (referred as Months 6, 9, 12 and so on) till the end of this study.

Participant milestones

Participant milestones
Measure	Pasireotide s.c. Overall Participants received pasireotide as a daily subcutaneous (s.c.) injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months).
Overall Study STARTED	30
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Pasireotide s.c. Overall Participants received pasireotide as a daily subcutaneous (s.c.) injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months).
Overall Study Adverse Event	3
Overall Study Abnormal Laboratory Value(s)	1
Overall Study Unsatisfactory Therapeutic Effect	8
Overall Study Withdrawal by Subject	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pasireotide s.c. Overall n=30 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months).
Age, Continuous	45.1 Years STANDARD_DEVIATION 15.48 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pasireotide s.c. <1200 μg/d n=5 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose \<1200 μg/day with median duration of 2.1 months.	Pasireotide s.c. 1200 to <1500 μg/d n=14 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose 1200 to \<1500 μg/day with median duration of 6.4 months.	Pasireotide s.c. ≥1500 μg/d n=7 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose ≥ 1500 μg/day with median duration of 16.6 months.	Pasireotide s.c. Overall n=26 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months).
Percentage of Participants With Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) Observed Response by Dose Class	20 percentage of responders Interval 9.0 to 43.6	28.6 percentage of responders Interval 9.0 to 43.6	14.3 percentage of responders Interval 9.0 to 43.6	23.1 percentage of responders Interval 9.0 to 43.6

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Pasireotide s.c. <1200 μg/d n=29 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose \<1200 μg/day with median duration of 2.1 months.	Pasireotide s.c. 1200 to <1500 μg/d Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose 1200 to \<1500 μg/day with median duration of 6.4 months.	Pasireotide s.c. ≥1500 μg/d Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose ≥ 1500 μg/day with median duration of 16.6 months.	Pasireotide s.c. Overall Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months).
Time to Tumor Response	12.2 months Interval 4.9 to 19.2	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Pasireotide s.c. <1200 μg/d n=30 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose \<1200 μg/day with median duration of 2.1 months.	Pasireotide s.c. 1200 to <1500 μg/d Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose 1200 to \<1500 μg/day with median duration of 6.4 months.	Pasireotide s.c. ≥1500 μg/d Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose ≥ 1500 μg/day with median duration of 16.6 months.	Pasireotide s.c. Overall Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months).
Summary Magnetic Resonance Imaging (MRI) Pituitary Tumor Volumes Core Study Baseline	4457.4 cubic millimeter (mm) Standard Deviation 4891.98	—	—	—
Summary Magnetic Resonance Imaging (MRI) Pituitary Tumor Volumes Month 9	2839.3 cubic millimeter (mm) Standard Deviation 2710.61	—	—	—
Summary Magnetic Resonance Imaging (MRI) Pituitary Tumor Volumes Month 27	2536 cubic millimeter (mm) Standard Deviation 2219.13	—	—	—
Summary Magnetic Resonance Imaging (MRI) Pituitary Tumor Volumes Month 63	456 cubic millimeter (mm) Standard Deviation 381.84	—	—	—
Summary Magnetic Resonance Imaging (MRI) Pituitary Tumor Volumes Month 75	1016 cubic millimeter (mm) Standard Deviation 872.39	—	—	—
Summary Magnetic Resonance Imaging (MRI) Pituitary Tumor Volumes Month 99	180 cubic millimeter (mm) Standard Deviation NA Due to one participant available for analysis standard deviation (SD) was not estimable.	—	—	—

SECONDARY outcome

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

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).

Outcome measures

Outcome measures
Measure	Pasireotide s.c. <1200 μg/d n=30 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose \<1200 μg/day with median duration of 2.1 months.	Pasireotide s.c. 1200 to <1500 μg/d Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose 1200 to \<1500 μg/day with median duration of 6.4 months.	Pasireotide s.c. ≥1500 μg/d Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose ≥ 1500 μg/day with median duration of 16.6 months.	Pasireotide s.c. Overall Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months).
Percentage of Participants With Symptoms of Acromegaly Headache - 0	46.7 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Headache - 1	26.7 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Headache - 2	6.7 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Headache - 3	0 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Headache - 4	0 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Headache - Not Done	20 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Perspiration - 0	20 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Perspiration - 1	33.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Perspiration - 2	23.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Perspiration - 3	3.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Perspiration - 4	0 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Perspiration - Not Done	20 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Paresthesiae - 0	50 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Paresthesiae - 1	16.7 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Paresthesiae - 2	13.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Paresthesiae - 3	0 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Paresthesiae - 4	0 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Paresthesiae - Not Done	20 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Fatigue - 0	26.7 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Fatigue - 1	26.7 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Fatigue - 2	13.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Fatigue - 3	13.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Fatigue - 4	0 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Fatigue - Not Done	20 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Osteoarthralgia - 0	40 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Osteoarthralgia - 1	23.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Osteoarthralgia - 2	10 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Osteoarthralgia - 3	3.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Osteoarthralgia - 4	3.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Osteoarthralgia - Not Done	20 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Carpal Tunnel Syndrome - 0	56.7 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Carpal Tunnel Syndrome - 1	10 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Carpal Tunnel Syndrome - 2	10 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Carpal Tunnel Syndrome - 3	3.3 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Carpal Tunnel Syndrome - 4	0 percentage of participants	—	—	—
Percentage of Participants With Symptoms of Acromegaly Carpal Tunnel Syndrome - Not Done	20 percentage of participants	—	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Pasireotide s.c. <1200 μg/d n=30 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose \<1200 μg/day with median duration of 2.1 months.	Pasireotide s.c. 1200 to <1500 μg/d Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose 1200 to \<1500 μg/day with median duration of 6.4 months.	Pasireotide s.c. ≥1500 μg/d Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose ≥ 1500 μg/day with median duration of 16.6 months.	Pasireotide s.c. Overall Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months).
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation In a Car, Stopped a Few Minutes in the Traffic - 1	10 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation In a Car, Stopped a Few Minutes in the Traffic - 2	0 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation In a Car, Stopped a Few Minutes in the Traffic - 3	0 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation In a Car, Stopped a Few Minutes in the Traffic - Not Done	16.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Reading - 0	36.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Reading - 1	23.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Reading - 2	23.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Reading - 3	0 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Reading - Not Done	16.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Watching TV - 0	23.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Watching TV - 1	33.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Watching TV - 2	23.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Watching TV - 3	3.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Watching TV - Not Done	16.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting, Inactive in a Public Place - 0	56.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting, Inactive in a Public Place - 1	20 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting, Inactive in a Public Place - 2	6.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting, Inactive in a Public Place - 3	0 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting, Inactive in a Public Place - Not Done	16.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Passenger in a Car, an Hour Without Break - 0	60 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Passenger in a Car, an Hour Without Break - 1	10 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Passenger in a Car, an Hour Without Break - 2	6.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Passenger in a Car, an Hour Without Break - 3	6.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Passenger in a Car, an Hour Without Break - Not Done	16.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Lying Down to Rest in the Afternoon - 0	13.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Lying Down to Rest in the Afternoon - 1	23.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Lying Down to Rest in the Afternoon - 2	23.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Lying Down to Rest in the Afternoon - 3	23.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Lying Down to Rest in the Afternoon - Not Done	16.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Talking to Someone - 0	76.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Talking to Someone - 1	6.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Talking to Someone - 2	0 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Talking to Someone - 3	0 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting and Talking to Someone - Not Done	16.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting Quietly After a Lunch Without Alcohol - 0	30 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting Quietly After a Lunch Without Alcohol - 1	23.3 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting Quietly After a Lunch Without Alcohol - 2	20 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting Quietly After a Lunch Without Alcohol - 3	10 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Sitting Quietly After a Lunch Without Alcohol - Not Done	16.7 percentage of participants	—	—	—
Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation In a Car, Stopped a Few Minutes in the Traffic - 0	73.3 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Pasireotide s.c. <1200 μg/d n=30 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose \<1200 μg/day with median duration of 2.1 months.	Pasireotide s.c. 1200 to <1500 μg/d n=30 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose 1200 to \<1500 μg/day with median duration of 6.4 months.	Pasireotide s.c. ≥1500 μg/d n=12 Participants Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose ≥ 1500 μg/day with median duration of 16.6 months.	Pasireotide s.c. Overall Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months).
Percentage of Participants With One or More Adverse Events (AEs)	80.0 percentage of participants	86.7 percentage of participants	91.7 percentage of participants	—

Adverse Events

Pasireotide s.c. <1200 μg/d

Serious events: 3 serious events

Other events: 21 other events

Deaths: 0 deaths

Pasireotide s.c. 1200 to <1500 μg/d

Serious events: 4 serious events

Other events: 25 other events

Deaths: 0 deaths

Pasireotide s.c. ≥1500 μg/d

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pasireotide s.c. <1200 μg/d n=30 participants at risk Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose \<1200 μg/day with median duration of 2.1 months.	Pasireotide s.c. 1200 to <1500 μg/d n=30 participants at risk Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose 1200 to \<1500 μg/day with median duration of 6.4 months.	Pasireotide s.c. ≥1500 μg/d n=12 participants at risk Participants received pasireotide as a daily s.c. injection every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 μg), with total daily dose ≥ 1500 μg/day with median duration of 16.6 months.
Endocrine disorders Acromegaly	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	8.3% 1/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Eye disorders Blindness	3.3% 1/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Hepatobiliary disorders Cholecystitis chronic	3.3% 1/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Infections and infestations Laryngitis	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	3.3% 1/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Infections and infestations Pilonidal cyst	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	8.3% 1/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Infections and infestations Tracheobronchitis	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	3.3% 1/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Injury, poisoning and procedural complications Tracheal obstruction	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	3.3% 1/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	3.3% 1/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	6.7% 2/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Musculoskeletal and connective tissue disorders Arthropathy	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	3.3% 1/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Musculoskeletal and connective tissue disorders Osteoarthritis	3.3% 1/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mucoepidermoid carcinoma	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	8.3% 1/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).
Psychiatric disorders Panic attack	0.00% 0/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	3.3% 1/30 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).	0.00% 0/12 • Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).

Other adverse events

Additional Information

Study Director

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 (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER