Trial Outcomes & Findings for Efficacy and Safety of Octreotide (MYCAPSSA™ [Formerly Octreolin™]) for Acromegaly (NCT NCT01412424)

NCT ID: NCT01412424

Last Updated: 2017-08-17

Results Overview

A responder was defined as a participant with a serum insulin-like growth factor-1 (IGF-1) concentration \< 1.3 times the upper limit of normal (adjusted for age and gender) and a growth hormone (GH) concentration \< 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 155 participants
• Primary outcome timeframe: End of the core treatment period (up to 7 months)
• Results posted on: 2017-08-17

Participant Flow

Participant milestones

Measure	Octreotide Capsules Participants received octreotide capsules orally twice a day for up to 13 months. Dosing started at 40 mg per day (20 in the morning + 20 in the evening) and increased to 60 mg per day (40 in the morning + 20 in the evening) or 80 mg per day (40 in the morning + 40 in the evening) if there was inadequate IGF-1 suppression.
Core Treatment Period STARTED	155
Core Treatment Period COMPLETED	102
Core Treatment Period NOT COMPLETED	53
Extension Treatment Period STARTED	88
Extension Treatment Period COMPLETED	82
Extension Treatment Period NOT COMPLETED	6

Reasons for withdrawal

Measure	Octreotide Capsules Participants received octreotide capsules orally twice a day for up to 13 months. Dosing started at 40 mg per day (20 in the morning + 20 in the evening) and increased to 60 mg per day (40 in the morning + 20 in the evening) or 80 mg per day (40 in the morning + 40 in the evening) if there was inadequate IGF-1 suppression.
Core Treatment Period Treatment Failure	24
Core Treatment Period Adverse Event	21
Core Treatment Period Patient Request	5
Core Treatment Period Lost to Follow-up	2
Core Treatment Period Sponsor Request	1
Extension Treatment Period Adverse Event	2
Extension Treatment Period Treatment Failure	2
Extension Treatment Period Patient Request	2

Baseline Characteristics

Efficacy and Safety of Octreotide (MYCAPSSA™ [Formerly Octreolin™]) for Acromegaly

Baseline characteristics by cohort

Measure	Octreotide Capsules n=155 Participants Participants received octreotide capsules orally twice a day for up to 13 months. Dosing started at 40 mg per day (20 in the morning + 20 in the evening) and increased to 60 mg per day (40 in the morning + 20 in the evening) or 80 mg per day (40 in the morning + 40 in the evening) if there was inadequate IGF-1 suppression.
Age, Continuous	54.2 Years STANDARD_DEVIATION 11.54 • n=5 Participants
Sex: Female, Male Female	88 Participants n=5 Participants
Sex: Female, Male Male	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	135 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	137 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: End of the core treatment period (up to 7 months)

Population: Modified intent-to-treat population: All enrolled participants who received any amount of study drug and who had at least 1 IGF-1 or GH assessment after the first dose of octreotide.

A responder was defined as a participant with a serum insulin-like growth factor-1 (IGF-1) concentration < 1.3 times the upper limit of normal (adjusted for age and gender) and a growth hormone (GH) concentration < 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.

Outcome measures

Measure	Octreotide 40 mg n=61 Participants Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg n=33 Participants Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg n=57 Participants Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.	Octreotide 40, 60, or 80 mg - All Participants n=151 Participants Participants received octreotide 40, 60, or 80 mg orally for up to 13 months.
Percentage of Responders at the End of the Core Treatment Period	86.9 Percentage of responders Interval 83.0 to 98.1	66.7 Percentage of responders Interval 48.2 to 82.0	40.4 Percentage of responders Interval 27.6 to 54.2	64.9 Percentage of responders Interval 58.4 to 74.2

PRIMARY outcome

Timeframe: End of the extension treatment period (up to 13 months)

Population: Extension intent-to-treat population: All participants who entered the extension treatment period and received any amount of study drug during the extension treatment period.

A responder was defined as a participant with a serum insulin-like growth factor-1 (IGF-1) concentration < 1.3 times the upper limit of normal (adjusted for age and gender) and a growth hormone (GH) concentration < 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.

Outcome measures

Measure	Octreotide 40 mg n=88 Participants Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.	Octreotide 40, 60, or 80 mg - All Participants Participants received octreotide 40, 60, or 80 mg orally for up to 13 months.
Percentage of Responders at the End of the Extension Treatment Period	78.4 Percentage of responders Interval 68.4 to 86.5	—	—	—

SECONDARY outcome

Timeframe: Baseline and the end of the core treatment period (up to 7 months)

Population: Modified intent-to-treat population: All enrolled participants who received any amount of study drug and who had at least 1 IGF-1 or GH assessment after the first dose of octreotide.

Percentage of participants with the following serum insulin-like growth factor-1 (IGF-1) and growth hormone (GH) concentrations at Baseline and at the end of the core treatment period (ECTP): IGF-1 < 1.3 times the upper limit of normal (ULN) and GH < 5.0 ng/mL, IGF-1 < 1.3 times ULN and GH < 1.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 5.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 2.5 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 1.0 ng/mL, IGF-1 < 1.3 times ULN, IGF-1 ≤ 1.0 times ULN, GH < 5.0 ng/mL, GH < 2.5 ng/mL, GH < 1.0 ng/mL, IGF-1 ≥ 1.3 times ULN and GH < 2.5 ng/mL, IGF-1 < 1.3 times ULN and GH ≥ 2.5 ng/mL, and IGF-1 ≥ 1.3 times ULN and GH ≥ 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.

Outcome measures

Measure	Octreotide 40 mg n=151 Participants Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.	Octreotide 40, 60, or 80 mg - All Participants Participants received octreotide 40, 60, or 80 mg orally for up to 13 months.
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 < 1.3 & GH < 5.0: Baseline	91.4 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 < 1.3 & GH < 5.0: ECTP	65.6 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 < 1.3 & GH < 1.0: Baseline	62.9 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 < 1.3 & GH < 1.0: ECTP	53.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≤ 1.0 & GH < 5.0: Baseline	63.6 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≤ 1.0 & GH < 5.0: ECTP	35.8 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≤ 1.0 & GH < 2.5: Baseline	61.6 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≤ 1.0 & GH < 2.5: ECTP	35.8 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≤ 1.0 & GH < 1.0: Baseline	43.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≤ 1.0 & GH < 1.0: ECTP	31.8 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 < 1.3: Baseline	91.4 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 < 1.3: ECTP	66.9 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≤ 1.0: Baseline	63.6 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≤ 1.0: ECTP	37.1 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period GH < 5.0: Baseline	100.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period GH < 5.0: ECTP	97.4 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period GH < 2.5: Baseline	96.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period GH < 2.5: ECTP	94.7 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period GH < 1.0: Baseline	66.2 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period GH < 1.0: ECTP	77.5 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≥ 1.3 & GH < 2.5: Baseline	7.3 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≥ 1.3 & GH < 2.5: ECTP	29.8 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 < 1.3 & GH ≥ 2.5: Baseline	2.6 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 < 1.3 & GH ≥ 2.5: ECTP	0.7 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≥ 1.3 & GH ≥ 2.5: Baseline	1.3 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period IGF-1 ≥ 1.3 & GH ≥ 2.5: ECTP	2.0 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Beginning of the fixed dose phase of the core treatment period and the end of the core treatment period (up to 7 months)

Population: Fixed dose population: All enrolled participants who received any amount of study drug, who had at least 1 IGF-1 or GH assessment after the first dose of octreotide, and who entered the fixed dose phase of the core treatment period.

Maintenance of response during the fixed dose phase of the core treatment period was defined as the percentage of participants with an insulin-like growth factor-1 (IGF-1) concentration < 1.3 times the upper limit of normal at the beginning of the fixed dose phase of the core treatment period and at the end of the core treatment period. IGF-1 concentration was determined in serum samples taken at the same visits growth hormone concentration was assessed.

Outcome measures

Measure	Octreotide 40 mg n=110 Participants Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.	Octreotide 40, 60, or 80 mg - All Participants Participants received octreotide 40, 60, or 80 mg orally for up to 13 months.
Maintenance of Response During the Fixed Dose Phase of the Core Treatment Period Beginning of the FDP of the CTP	82.7 Percentage of participants	—	—	—
Maintenance of Response During the Fixed Dose Phase of the Core Treatment Period End of the CTP	80.0 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Beginning and the end of the extension treatment period (up to 6 months)

Population: Extension intent-to-treat population: All participants who entered the extension treatment period and received any amount of study drug during the extension treatment period.

Percentage of participants with the following serum insulin-like growth factor-1 (IGF-1) and growth hormone (GH) concentrations at the beginning (BETP) and at the end (EETP) of the extension treatment period: IGF-1 < 1.3 times the upper level of normal (ULN) and GH < 5.0 ng/mL, IGF-1 < 1.3 times ULN and GH < 1.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 5.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 2.5 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 1.0 ng/mL, IGF-1 < 1.3 times ULN, IGF-1 ≤ 1.0 times ULN, GH < 5.0 ng/mL, GH < 2.5 ng/mL, GH < 1.0 ng/mL, IGF-1 ≥ 1.3 times ULN and GH < 2.5 ng/mL, IGF-1 < 1.3 times ULN and GH ≥ 2.5 ng/mL, and IGF-1 ≥ 1.3 times ULN and GH ≥ 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.

Outcome measures

Measure	Octreotide 40 mg n=88 Participants Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.	Octreotide 40, 60, or 80 mg - All Participants Participants received octreotide 40, 60, or 80 mg orally for up to 13 months.
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 < 1.3 & GH < 5.0: BETP	84.1 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 < 1.3 & GH < 5.0: EETP	79.5 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 < 1.3 & GH < 1.0: BETP	69.3 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 < 1.3 & GH < 1.0: EETP	68.2 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≤ 1.0 & GH < 5.0: BETP	48.9 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≤ 1.0 & GH < 5.0: EETP	50.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≤ 1.0 & GH < 2.5: BETP	48.9 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≤ 1.0 & GH < 2.5: EETP	50.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≤ 1.0 & GH < 1.0: BETP	42.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≤ 1.0 & GH < 1.0: EETP	44.3 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 < 1.3: BETP	84.1 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 < 1.3: EETP	79.5 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≤ 1.0: BETP	48.9 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≤ 1.0: EETP	50.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period GH < 5.0: BETP	100.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period GH < 5.0: EETP	97.7 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period GH < 2.5: BETP	98.9 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period GH < 2.5: EETP	95.5 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period GH < 1.0: BETP	83.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period GH < 1.0: EETP	83.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≥ 1.3 & GH < 2.5: BETP	14.8 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≥ 1.3 & GH < 2.5: EETP	17.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 < 1.3 & GH ≥ 2.5: BETP	0.0 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 < 1.3 & GH ≥ 2.5: EETP	1.1 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≥ 1.3 & GH ≥ 2.5: BETP	1.1 Percentage of participants	—	—	—
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period IGF-1 ≥ 1.3 & GH ≥ 2.5: EETP	3.4 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Beginning of the extension treatment period and the end of the extension treatment period (up to 13 months)

Population: Extension intent-to-treat population: All participants who entered the extension treatment period and received any amount of study drug during the extension treatment period.

Maintenance of an insulin-like growth factor-1 (IGF-1) response during the extension treatment period was defined as the percentage of participants with an IGF-1 concentration < 1.3 times the upper limit of normal at the beginning of the extension treatment period and at the end of the extension treatment period. IGF-1 concentration was determined in serum samples taken at the same visits growth hormone concentration was assessed.

Outcome measures

Measure	Octreotide 40 mg n=74 Participants Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.	Octreotide 40, 60, or 80 mg - All Participants Participants received octreotide 40, 60, or 80 mg orally for up to 13 months.
Maintenance of Response During the Extension Treatment Period	87.8 Percentage of participants Interval 78.2 to 94.3	—	—	—

SECONDARY outcome

Timeframe: Baseline and the end of the extension treatment period (up to 13 months)

Population: Extension intent-to-treat population: All participants who entered the extension treatment period and received any amount of study drug during the extension treatment period.

The severity (absent, mild, moderate, severe) of the 5 acromegaly symptoms headache, perspiration, asthenia, swelling of extremities, and joint pain was assessed at Baseline and at the end of the extension treatment period. The percentage of participants with improved or maintained (no change) acromegaly symptoms from Baseline at the end of the extension treatment period is reported.

Outcome measures

Measure	Octreotide 40 mg n=88 Participants Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.	Octreotide 40, 60, or 80 mg - All Participants Participants received octreotide 40, 60, or 80 mg orally for up to 13 months.
Percentage of Participants With Improved or Maintained Acromegaly Symptoms at the End of the Extension Treatment Period Maintained	27 Percentage of participants Interval 18.3 to 37.8	—	—	—
Percentage of Participants With Improved or Maintained Acromegaly Symptoms at the End of the Extension Treatment Period Improved	57 Percentage of participants Interval 45.8 to 67.3	—	—	—

SECONDARY outcome

Timeframe: Baseline and the end of the extension treatment period (up to 13 months)

Population: Extension intent-to-treat population: All participants who entered the extension treatment period and received any amount of study drug during the extension treatment period.

Reported is the percentage of participants who had ≥ 1, 2, or 3 of the 5 symptoms of acromegaly (headaches, perspiration, asthenia, swelling of extremities, or joint pain) of any severity (mild, moderate, or severe). This was a post hoc analysis.

Outcome measures

Measure	Octreotide 40 mg n=88 Participants Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.	Octreotide 40, 60, or 80 mg - All Participants Participants received octreotide 40, 60, or 80 mg orally for up to 13 months.
Percentage of Participants With ≥ 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period 1 Symptom - Baseline	78 Percentage of participants	—	—	—
Percentage of Participants With ≥ 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period 1 Symptom - End of the extension treatment period	65 Percentage of participants	—	—	—
Percentage of Participants With ≥ 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period 2 Symptoms - Baseline	61 Percentage of participants	—	—	—
Percentage of Participants With ≥ 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period 2 Symptoms - End of the extension treatment period	43 Percentage of participants	—	—	—
Percentage of Participants With ≥ 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period 3 Symptoms - Baseline	43 Percentage of participants	—	—	—
Percentage of Participants With ≥ 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period 3 Symptoms - End of the extension treatment period	25 Percentage of participants	—	—	—

Adverse Events

Octreotide 40 mg

Serious events: 9 serious events

Other events: 103 other events

Deaths: 1 deaths

Octreotide 60 mg

Serious events: 7 serious events

Other events: 51 other events

Deaths: 0 deaths

Octreotide 80 mg

Serious events: 8 serious events

Other events: 31 other events

Deaths: 1 deaths

Serious adverse events

Measure	Octreotide 40 mg n=155 participants at risk Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg n=91 participants at risk Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg n=58 participants at risk Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.
Hepatobiliary disorders Cholelithiasis	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Hepatobiliary disorders Bile duct obstruction	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Hepatobiliary disorders Bile duct stone	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Hepatobiliary disorders Jaundice	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Nervous system disorders Convulsion	1.3% 2/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Nervous system disorders Headache	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Nervous system disorders Sciatica	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Nervous system disorders Syncope	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Nervous system disorders Transient ischemic attack	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Infections and infestations Chronic sinusitis	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Infections and infestations Corneal abscess	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Infections and infestations Herpes simplex ophthalmic	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Infections and infestations Sepsis	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Infections and infestations Urinary tract infection	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Cardiac disorders Acute myocardial infarction	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Cardiac disorders Bradycardia	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Cardiac disorders Cardiac failure	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Musculoskeletal and connective tissue disorders Intervertebral disc protusion	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Musculoskeletal and connective tissue disorders Polymyalgia Rheumatica	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Ear and labyrinth disorders Tinnitus	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Ear and labyrinth disorders Vertigo	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
General disorders Impaired healing	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
General disorders Pyrexia	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Blood and lymphatic system disorders Spleen disorder	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Gastrointestinal disorders Melaena	0.65% 1/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Investigations Transaminases increased	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic neoplasm	0.00% 0/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	0.00% 0/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.

Other adverse events

Measure	Octreotide 40 mg n=155 participants at risk Participants received octreotide 20 mg orally twice a day for up to 13 months.	Octreotide 60 mg n=91 participants at risk Participants received octreotide 40 mg in the morning and octreotide 20 mg in the evening orally for up to 13 months.	Octreotide 80 mg n=58 participants at risk Participants received octreotide 40 mg in the morning and octreotide 40 mg in the evening orally for up to 13 months.
Gastrointestinal disorders Abdominal distension	4.5% 7/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	4.4% 4/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Gastrointestinal disorders Abdominal pain	3.2% 5/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	7.7% 7/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Gastrointestinal disorders Abdominal pain upper	6.5% 10/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	2.2% 2/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	5.2% 3/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Gastrointestinal disorders Diarrhoea	11.6% 18/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	12.1% 11/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	6.9% 4/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Gastrointestinal disorders Dyspepsia	7.1% 11/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	2.2% 2/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.7% 1/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Gastrointestinal disorders Flatulence	6.5% 10/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	3.4% 2/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Gastrointestinal disorders Nausea	19.4% 30/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	15.4% 14/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	10.3% 6/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Gastrointestinal disorders Vomiting	2.6% 4/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	3.3% 3/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	6.9% 4/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
General disorders Asthenia	17.4% 27/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	12.1% 11/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	13.8% 8/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
General disorders Oedema peripheral	12.3% 19/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	8.8% 8/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	8.6% 5/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Hepatobiliary disorders Cholelithiasis	2.6% 4/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	3.3% 3/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	5.2% 3/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Infections and infestations Influenza	3.9% 6/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	4.4% 4/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	5.2% 3/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Infections and infestations Nasopharyngitis	3.2% 5/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	4.4% 4/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	8.6% 5/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Infections and infestations Upper respiratory tract infection	3.9% 6/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	2.2% 2/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	5.2% 3/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Metabolism and nutrition disorders Hypoglycaemia	1.9% 3/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	2.2% 2/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	5.2% 3/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Musculoskeletal and connective tissue disorders Arthralgia	16.1% 25/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	22.0% 20/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	19.0% 11/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Musculoskeletal and connective tissue disorders Myalgia	1.3% 2/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	2.2% 2/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	5.2% 3/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Musculoskeletal and connective tissue disorders Neck pain	1.9% 3/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	5.2% 3/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Nervous system disorders Dizziness	5.2% 8/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	1.1% 1/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	3.4% 2/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Nervous system disorders Headache	28.4% 44/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	19.8% 18/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	34.5% 20/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Skin and subcutaneous tissue disorders Hyperhidrosis	14.8% 23/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	9.9% 9/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	10.3% 6/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.
Vascular disorders Hypertension	3.9% 6/155 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	4.4% 4/91 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.	5.2% 3/58 Safety population: All participants enrolled in the study who received any amount of the study drug. The total number of participants with adverse events is greater than the 155 participants enrolled in the study since this was a dose-escalation study and adverse events occurred at all dose levels.

Additional Information

Shlomo Melmed, MD

Cedars-Sinai Medical Center

Phone: 310 423-4691

Email: melmed@csmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee The results of the study cannot be published for a period of up to 150 days, 60 days for sponsor review and 90 days for patent protection. In addition, the first publication may only occur after the first multi-center publication or, if no such multi-center publication is made, 12-18 months after completion of the study at all study sites.
• Publication restrictions are in place

Restriction type: OTHER