Trial Outcomes & Findings for Extension Study to Assess the Safety and Efficacy of Pasireotide in Participants With Cushing's Disease (NCT NCT00171951)

NCT ID: NCT00171951

Last Updated: 2021-06-02

Results Overview

A participant was considered a responder if the mean UFC from the two 24-hour urine samples collected at Month 6 was within normal limits. The normal range for UFC is 55 to 276 nmol/day.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Month 6

Results posted on

2021-06-02

Participant Flow

The study included participants with Cushing's disease who received 15 days of pasireotide treatment in the Core Study CSOM230B2208 (NCT00088608). This study was an extension study of the Core Study.

Participant milestones

Participant milestones
Measure	Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC Participants received pasireotide 600 micrograms (μg) twice daily (BID) subcutaneously (SC) to achieve or maintain urinary free cortisol (UFC) normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Overall Study STARTED	19
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC Participants received pasireotide 600 micrograms (μg) twice daily (BID) subcutaneously (SC) to achieve or maintain urinary free cortisol (UFC) normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Overall Study Adverse Event	1
Overall Study Abnormal Laboratory Values	2
Overall Study Unsatisfactory Therapeutic Effect	3
Overall Study Participants Withdrew Consent	3
Overall Study New Cancer Therapy	5
Overall Study Reason not Specified	2

Baseline Characteristics

Extension Study to Assess the Safety and Efficacy of Pasireotide in Participants With Cushing's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC n=19 Participants Participants received pasireotide 600 μg BID SC to achieve or maintain UFC normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Age, Continuous	43.0 years STANDARD_DEVIATION 11.62 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 6

Population: Primary Efficacy Population included participants from ITT whose mean UFC at core-baseline, based on at least 2 UFC samples, was \>1.0x upper limit of normal (ULN) or for whom the one and only UFC sample available at baseline was \>2.0xULN.

A participant was considered a responder if the mean UFC from the two 24-hour urine samples collected at Month 6 was within normal limits. The normal range for UFC is 55 to 276 nmol/day.

Outcome measures

Outcome measures
Measure	Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC n=18 Participants Participants received pasireotide 600 μg BID SC to achieve or maintain UFC normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.	Pasireotide 900 μg BID SC Participants received 900 μg BID SC if UFC levels were increased at any time, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Percentage of Responders With Mean Urinary Free Cortisol (UFC) Within Normal Limits	22.2 percentage of responders Interval 6.4 to 47.6	—

PRIMARY outcome

Timeframe: Core Baseline, Days 14/15 (Core study), Months 6, 12, 24 and 102

Population: Primary Efficacy Population included participants from ITT whose mean UFC at core-baseline, based on at least 2 UFC samples, was \>1.0x ULN or for whom the one and only UFC sample available at baseline was \>2.0xULN. Number analyzed is the number of participants with data available for analysis at the given time point.

24-hour urine samples were collected to obtain mean UFC measurements. A negative mean change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC n=18 Participants Participants received pasireotide 600 μg BID SC to achieve or maintain UFC normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.	Pasireotide 900 μg BID SC Participants received 900 μg BID SC if UFC levels were increased at any time, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Change From Baseline in Mean Urinary Free Cortisol (UFC) Core Baseline	1219.74 nanomoles per 24 hours (nmol/24h) Standard Deviation 752.9	—
Change From Baseline in Mean Urinary Free Cortisol (UFC) Change from Core Baseline to Day 14/Day 15	-710.57 nanomoles per 24 hours (nmol/24h) Standard Deviation 740.6	—
Change From Baseline in Mean Urinary Free Cortisol (UFC) Change from Core Baseline to Month 6	-801.85 nanomoles per 24 hours (nmol/24h) Standard Deviation 819.4	—
Change From Baseline in Mean Urinary Free Cortisol (UFC) Change from Core Baseline to Month 12	-1202.1 nanomoles per 24 hours (nmol/24h) Standard Deviation 1084.1	—
Change From Baseline in Mean Urinary Free Cortisol (UFC) Change from Core Baseline to Month 24	-1241.1 nanomoles per 24 hours (nmol/24h) Standard Deviation 925.6	—
Change From Baseline in Mean Urinary Free Cortisol (UFC) Change from Core Baseline to Month 102	-2417.0 nanomoles per 24 hours (nmol/24h) Standard Deviation NA Due to one participant available for analysis standard deviation (SD) was not estimable.	—

SECONDARY outcome

Timeframe: Up to approximately 106 months

Population: Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.

An AE was any undesirable sign, symptom or medical condition occurring after starting study drug even if the event is not considered to be related to study drug. AEs were assessed according to incident dose group: Pasireotide 1200 μg sc total daily dose (TDD), Pasireotide 1800 μg SC TDD and Pasireotide SC Any Dose. The incident dose for an AE was the last total daily dose administered on or prior to the AE onset date.

Outcome measures

Outcome measures
Measure	Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC n=19 Participants Participants received pasireotide 600 μg BID SC to achieve or maintain UFC normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.	Pasireotide 900 μg BID SC n=8 Participants Participants received 900 μg BID SC if UFC levels were increased at any time, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Number of Participants Who Had At Least One Adverse Event (AE)	19 Participants	8 Participants

SECONDARY outcome

Timeframe: Core Baseline, Day 15 (Core study), Months 6, 12, 24, and Month 105 (end of the study)

Blood samples were withdrawn to obtain the serum cortisol levels. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC n=18 Participants Participants received pasireotide 600 μg BID SC to achieve or maintain UFC normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.	Pasireotide 900 μg BID SC Participants received 900 μg BID SC if UFC levels were increased at any time, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Change From Baseline in Serum Cortisol Levels Core Baseline	723.60 nanomoles per liters (nmol/L) Standard Deviation 221.5	—
Change From Baseline in Serum Cortisol Levels Change from Core Baseline to Day 15	-25.96 nanomoles per liters (nmol/L) Standard Deviation 125.1	—
Change From Baseline in Serum Cortisol Levels Change from Core Baseline to Month 6	-150.60 nanomoles per liters (nmol/L) Standard Deviation 308.9	—
Change From Baseline in Serum Cortisol Levels Change from Core Baseline to Month 12	-66.06 nanomoles per liters (nmol/L) Standard Deviation 301.9	—
Change From Baseline in Serum Cortisol Levels Change from Core Baseline to Month 24	-227.53 nanomoles per liters (nmol/L) Standard Deviation 283.1	—
Change From Baseline in Serum Cortisol Levels Change from Core Baseline to Month 105	-166.00 nanomoles per liters (nmol/L) Standard Deviation NA Due to one participant available for analysis SD was not estimable.	—

SECONDARY outcome

Timeframe: Day 15 (Core study) and Month 6

Population: Pharmacokinetic (PK) Population included participants from ITT who had at least one post dosing PK assessment up to the implementation of Amendment 2 when no further blood samples were collected for PK assessment (24 May 2007).

Participants with Cushing's disease were considered responders if mean UFC levels from the 24-hour urine collections at Day 15 (Core study) and at extension Month 6, were within normal limits. Ctrough levels of pasireotide were measured at Day 15 of Core study and Month 6.

Outcome measures

Outcome measures
Measure	Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC n=4 Participants Participants received pasireotide 600 μg BID SC to achieve or maintain UFC normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.	Pasireotide 900 μg BID SC Participants received 900 μg BID SC if UFC levels were increased at any time, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Plasma Trough Concentrations (Ctrough) of Pasireotide in UFC Responders Day 15 (Core Study)	7.0 nanograms per milliliter (ng/mL) Standard Deviation 4.3	—
Plasma Trough Concentrations (Ctrough) of Pasireotide in UFC Responders Month 6	17.4 nanograms per milliliter (ng/mL) Standard Deviation 11.6	—

SECONDARY outcome

Timeframe: Core Baseline, Day 15 (Core study), Months 6, 12, 24 and Month 105 (end of the study)

Blood samples were withdrawn to obtain the ACTH levels. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC n=18 Participants Participants received pasireotide 600 μg BID SC to achieve or maintain UFC normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.	Pasireotide 900 μg BID SC Participants received 900 μg BID SC if UFC levels were increased at any time, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels Core Baseline	13.72 picomoles per litre (pmol/L) Standard Deviation 11.0	—
Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels Change from Core Baseline to Day 15	-1.28 picomoles per litre (pmol/L) Standard Deviation 7.1	—
Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels Change from Core Baseline to Month 6	-3.36 picomoles per litre (pmol/L) Standard Deviation 9.4	—
Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels Change from Core Baseline to Month 12	-3.60 picomoles per litre (pmol/L) Standard Deviation 15.2	—
Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels Change from Core Baseline to Month 24	-4.50 picomoles per litre (pmol/L) Standard Deviation 8.3	—
Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels Change from Core Baseline to Month 105	0.00 picomoles per litre (pmol/L) Standard Deviation NA Due to one participant available for analysis SD was not estimable.	—

SECONDARY outcome

Timeframe: Baseline to end of the study

Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.

Outcome measures

Outcome data not reported

Adverse Events

Pasireotide 600 μg BID SC

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Pasireotide 900 μg BID SC

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pasireotide 600 μg BID SC n=19 participants at risk Participants received pasireotide 600 μg BID SC, to achieve or maintain UFC normalization.	Pasireotide 900 μg BID SC n=8 participants at risk Participants received 900 μg BID SC if UFC levels were increased at any time, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.
Infections and infestations Urinary tract infection	0.00% 0/19 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.	12.5% 1/8 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.
Injury, poisoning and procedural complications Skin injury	0.00% 0/19 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.	12.5% 1/8 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/19 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.	12.5% 1/8 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.
Nervous system disorders Convulsion	5.3% 1/19 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.	0.00% 0/8 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.
Respiratory, thoracic and mediastinal disorders Pneumothorax	5.3% 1/19 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.	0.00% 0/8 • Up to approximately 106 months Safety Population included participants from ITT Population. ITT Population included participants who completed 15 days of treatment in the Core study, experienced significant clinical benefit without any unacceptable AEs, and received at least 1 dose in the extension period.

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