Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Pasireotide · 8 trials · 11 indications
Percentage of patients who received clinical benefit in symptom (diarrhea and/or flushing) improvement as: Diarrhea (D)+Flushing (F): Patients with a daily mean number (#) of at least four bowel movements and a total of five or more flushing episodes. Clinical Benefit Response Criteria (CBRC): \<4 daily mean bowel movements AND at least 20% reduction from Baseline in the daily mean # of bowel movements AND any reduction in the total # of flushing episodes compared with Baseline. (D) Patients with a daily mean # of at least four bowel movements and a total # of \<5 flushing episodes. (CBRC) \<4 daily mean bowel movements AND at least a 20% reduction from Baseline in the daily mean # of bowel movements. (F) Patients with a total # of at least 14 flushing episodes and a daily mean # of \<4 bowel movements (CBRC) At least a 30% reduction from Baseline in the total # of flushing episodes.
A responder in the primary efficacy analysis was a patient with a mUFC≤ULN at Month 6 and whose dose was not increased prior to Month 6.
Number of participants with response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."
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.
24-hour urine samples were collected to obtain mean UFC measurements. A negative mean change from baseline indicates improvement.
Complete Symptom Control: an average of ≤ 3 bowel movements per day for at least 15 consecutive days, with no more than 3 episodes on any given day, and no episodes of flushing over the time interval being studied. Partial Symptom Control: an average of \< 4 bowel movements per day for at least 15 consecutive days, with no more than 6 episodes per given day, and an average of fewer than 2 daily flushing episodes over the same given time interval. Treatment failure: Failure to obtain partial or complete treatment success over a consecutive 15-day period at a constant dose level.
The primary outcome is the number of hypoglycemic events occurring.
in patients with acromegaly and in patients with carcinoid disease
| Arm | Type | Description |
|---|---|---|
| Pasireotide LAR | ACTIVE_COMPARATOR | Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed. |
| Octreotide LAR | ACTIVE_COMPARATOR | Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed. |
| Pasireotide 600 ug | EXPERIMENTAL | At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was \<= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country. |
| Pasireotide 900 ug | EXPERIMENTAL | At randomization, participants received 900 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was \<= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country. |
| Arm A (Everolimus alone) | EXPERIMENTAL | CURRENTLY CLOSED TO ACCRUAL--Everolimus alone followed by Everolimus + Pasireotide at the time of progression |
| Arm B (Pasireotide alone) | EXPERIMENTAL | CURRENTLY CLOSED TO ACCRUAL--Pasireotide alone followed by Everolimus + Pasireotide at the time of progression |
| Arm C (Everolimus + Pasireotide) | EXPERIMENTAL | CURRENTLY CLOSED TO ACCRUAL |
| Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC | EXPERIMENTAL | 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. |
| Pasireotide | EXPERIMENTAL | - |
| SOM230 LAR | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Pasireotide | DRUG | Pasireotide LAR 60mg i.m. injection - patients may also receive pasireotide 600 µg s.c 3 times a day for symptom control as needed |
| Octreotide | DRUG | Octreotide LAR 40mg i.m. depot injection - Patients may also receive octreotide 100 µg s.c. 3 times a day for symptom control as needed |
| Everolimus | DRUG | Everolimus 10 mg daily continuously (switch to 2-drug combination at progression if no intolerable toxicity) |
| Everolimus and Pasireotide | DRUG | Everolimus 10 mg daily continuously together with Pasireotide 1200 mcg bid for 4 weeks followed by Pasireotide long acting release (LAR) 60 mg i.m. once every 4 weeks |
| Pasireotide (SOM230) | DRUG | Open label. Patients received starting dose of 300 µg of study drug subcutaneously (s.c.) twice (total of 600 µg ) daily for three days, which could be increased in 150 µg increments up to 900 µg twice daily (total 1800 µg daily) if control of symptoms was not achieved. Prior sponsor agreement was required for a higher dose. A dose of 2400 µg/day was the maximum allowed. Dose reductions of 300 µg/day were allowed at any time if unacceptable toxicity occurred. |
Inclusion criteria: * Male or female patients aged 18 or greater * Patients with carcinoid tumors and symptoms (diarrhea and flushing) that are not adequately controlled by somatostatin analogues. * Female patients of child bearing potential must have a negative pregnancy test at baseline. * Patien...
Pasireotide is an investigational small molecule being studied for multiple conditions, including hepatic cirrhosis, thyroid cancer, acromegaly, symptomatic refractory resistant carcinoid disease, hyperinsulinemic hypoglycemia, and Cushing's disease. It is developed by Novartis AG and has completed four clinical trials with a total enrollment of 648 participants.
Pasireotide is a somatostatin analog that targets somatostatin receptors. It is being studied for its effects in conditions like acromegaly and carcinoid tumors, where it may help regulate hormone secretion. The drug is administered subcutaneously and is in clinical development for multiple indications.
Pasireotide is developed by Novartis AG, a multinational pharmaceutical company traded under the ticker symbol NVS. The drug is currently in clinical development and has completed trials in the United States and other countries for conditions such as acromegaly and carcinoid tumors.
Pasireotide is in Phase 1 clinical development, though it has completed trials in Phase 2 and Phase 3. The most recent trial, a pharmacokinetics study in hepatic impairment, was Phase 1. All four trials are completed, and the drug remains investigational, not yet approved by regulatory authorities.
Pasireotide has completed four clinical trials: NCT00088582 (Phase 2, acromegaly, 62 participants), NCT00088595 (Phase 2, metastatic carcinoid tumors, 45 participants), NCT00690430 (Phase 3, symptomatic refractory resistant carcinoid disease, 186 participants), and NCT00698464 (Phase 1, hepatic cirrhosis, 34 participants). All trials are completed.
Pasireotide is also known as SOM230, as indicated in clinical trial titles. For example, NCT00088582 refers to SOM230 in acromegalic patients, and NCT00698464 evaluates subcutaneous pasireotide (SOM230). Both names refer to the same investigational drug developed by Novartis.